MXPA06009036A - Combination of proton pump inhibitor, buffering agent, and nonsteroidal anti-inflammatory agent - Google Patents

Abstract

Pharmaceutical compositions comprising a proton pump inhibitor, one or more buffering agent and a nonsteroidal anti-inflammatory drug are described. Methods are described for treating gastric acid related disorders and treating inflammatory disorders, using pharmaceutical compositions comprising a proton pump inhibitor, a buffering agent, and a nonsteroidal anti-inflammatory drug.

Description

COMBINATION OF PROTON PUMP INHIBITOR, AGENT NON-STEROIDAL ANTI-INFLAMMATORY DAMAGER AND DRUG CROSS REFERENCE TO RELATED REQUESTS This application claims priority of the provisional US patent application. Serial Number 60 / 543,636 filed on February 10, 2004, which is hereby incorporated by reference in its entirety. FIELD OF THE INVENTION The present invention relates to pharmaceutical compositions comprising a proton pump inhibitor, a buffering agent, and a non-steroidal anti-inflammatory drug. Methods for making pharmaceutical compositions and use of pharmaceutical compositions for the treatment of disease are described. BACKGROUND OF THE INVENTION PROTON PUMP INHIBITOR Proton pump inhibitors (PPIs = Proton Pumps inhibitors) are a class of labile acid pharmaceutical compounds that block the routes of gastric acid secretion. Exemplary proton pump inhibitors include omeprazole (Prilosec ™), lansoprazole (Prevacid ™), esomeprazole (Nexium ™), rabeprazole (Aciphex ™), pantoprazole (Protonix ™), pariprazole, tenatoprazole, and leminoprazole. Drugs of this class suppress the secretion of gastrointestinal acids by the specific inhibition of the enzyme system H + / K + -ATPase on the secretory surface of the gastrointestinal parietal cell. Most proton pump inhibitors are susceptible to acid degradation and as such are rapidly destroyed in an acidic pH environment in the stomach. Therefore, proton pump inhibitors are often administered as. dosage forms of enteric coating in order to allow release of the drug into the duodenum after having passed through the stomach. If the enteric coating of these formulated products is broken (for example during grinding to form a liquid dosage form, or by chewing a granular enteric coating tablet or capsule), or if a co-administered cushioning agent fails to neutralize in a If the gastrointestinal pH is sufficient, the uncoated drug is exposed to stomach acids and can be degraded. Omeprazole, a substituted bi-cyclic aryl imidazole, 5-methoxy-2 [(4-methoxy-3,5-dimethyl-2-pyridinyl) methyl] sulfinyl] -IH-benzimidazole, is a proton pump inhibitor that inhibits the secretion of gastrointestinal acids. The patent of the U.S.A. Number 4,786,505 granted to Lovgren et al. , shows that a pharmaceutical oral solid dosage form of omeprazole should be protected from contact with acidic gastrointestinal juices by an enteric coating to maintain its pharmaceutical activity and describes an enteric coated omeprazole preparation containing one or more sub-coatings between the core material and the enteric coating. Pharmaceutical compositions without enteric coating have also been described, which facilitate the immediate release of the pharmaceutically active ingredient to the stomach and allow stomach absorption of the pharmaceutical agents. The use of compounds without enteric coating involves the administration of one or more buffering agents with a labile acid proton pump inhibitor. The buffering agent is considered to prevent substantial degradation of the labile acid pharmaceutical agent in the acidic environment of the stomach by raising the pH of the stomach. See, for example, US patents. numbers 5,840,737; 6,489,346; and 6,645,998. Proton pump inhibitors are typically prescribed for short-term treatment of active duodenal ulcers, gastrointestinal ulcers, gastroesophageal reflux disease (GERD), severe erosive esophagitis, symptomatic GERD of poor response, and pathological hyper secretory conditions such like the Zollinger Ellison syndrome. These aforementioned conditions commonly arise in healthy or critically ill patients of all ages and may be accompanied by significant upper gastrointestinal bleeding. It is considered that omeprazole, lansoprazole and other proton pump inhibitors reduce the production of gastrointestinal acid by inhibiting H + / K + -ATPase from the parietal cell, which is the final common route for gastrointestinal acid secretion. See Fellenius et al. , Substituted Benzimidazoles Inhibit Gastrointestinal Acid Secretion by Blocking H + / K + -ATPase, Nature, 290: 159-161 (1981); Wallmark et al. , The Relationship Between Gastrointestinal Acid Secretion and Gastrointestinal H + / K + -ATPase Activity, "Biol. Chem, 260: 13681-13684 (1985), and Fryklund et al., Function and Structure of Parietal Cells After H + / K + -ATPase Blockade , Am. J ". Physio. , 254 (1988). Proton pump inhibitors have the ability to act as weak bases that reach the parietal cells from the blood and diffuse into the secretory canaliculi. There, the drugs are proposed and in this way they are trapped. The protonated compound can rearrange to form a sulfenamide that can interact covalently with sulfhydryl group at critical sites in the extracellular (luminal) domain of the H + / K + -ATPase extending across the membrane. See, for example, Hardman et al. , Goodman & Gilman's Che Pharmacological Basis of Therapeutics, 907 (9th ed., 1996). As such, proton pump inhibitors are prodrugs that must be activated within the parietal cells to be effective. The specificity of the effects of the proton pump inhibitory agents also depends on: a) the selective distribution of H + / K + -ATPase; b) the requirement for acidic conditions when catalyzing the generation of the reactive inhibitor; c) the trampling of the protonated drug and the cationic sulfenamide within the acidic canaliculi and adjacent to the target enzyme. Non-steroidal anti-inflammatory drugs. Nonsteroidal anti-inflammatory drugs ("NSAIDs" = Nonsteroidal anti-inflammatory drugs) are among the most commonly prescribed and used drugs in the world. The ability of NSAIDs to treat inflammatory disorders is attributed to their ability to inhibit cyclooxygenase, the enzyme that responds by the bio-synthesis of prostaglandins and certain autocoid inhibitors, including inhibitors of lipoxygenase and cyclooxygenase (such as cyclooxygenase-I and cyclooxygenase- II). However, despite the therapeutic benefits of NSAIDs, their use is often limited by an increased risk of gastrointestinal side effects, particularly superior gastrointestinal side effects such as peptic ulcers and dyspeptic symptoms. For example, studies have indicated that during treatment with NSAIDs, the relative risk of developing a gastric ulcer is increased by a factor of 40-50, the relative risk of developing a duodenal ulcer is increased by a factor of 8-10 and the risk Relative to developing a complication of ulcer such as bleeding or perforation of the stomach is increased by a factor of 1.5-5. See for example McCarty Ds M., Gastroenterology 1989, 96: 662; and Hawkey C., BMJ 1990; 300: 278. In addition, dyspeptic symptoms are experienced in 30-60% of patients treated with NSAIDs. See Larkai E.N., Am. J. Gas. 1987; 82: 1153. Additionally, NSAIDs are typically the prescribed treatment for chronic diseases such as rheumatoid arthritis and osteoarthritis, seen more often in the elderly population. Compliance is especially important in older and frail patients, who have the highest risk of developing a life-threatening complication of treatment with NSAIDs, such as bleeding or perforation. It has been reported that 50% of all peptic ulcer deaths occur in users of NSAIDs, and that 68% of these deaths occur in patients over 75 years of age. See Catford Health Trends 1986, 18: 38; and Guess, J. Clin. Epide iol. , 1988, 41:35. Attempts have been made to modify the structure of the NSAIDs in order to avoid undesirable side effects. The new family of NSAIDs that selectively inhibits only cyclooxygenase-II ("COX-II inhibitors") represents a similar advance.

Although COX-II inhibitors are thought to cause less irritation to the stomach than previous nonselective NSAIDs still have the potential to cause irritation, ulceration, bleeding and perforation of the lining of the stomach. In addition, there is emerging evidence of a protective association between aspirin / NSAIDs and various types of cancer such as esophageal cancer, lung cancer, colorectal cancer, breast cancer and prostate cancer. See for example Randall E. Harris et al. , Inverse Association of Breast Cancer and NSAIDs: Results from the Women's Heal th Initiative (WH), AACR, Volume 44 (March 2003); Gonzalez-Perez A; Effects of Non-Steroidal Anti-Inflammatory Drugs on Cancer If you try Other than the Colon and Rectum: a Meta-Analysis, BMC Cancer 3 (1): 28 (2003); DA Corley et al. , Protective Association of Aspirin / NSAIDs and Esophageal Cancer: A Systematic Review and Meta-Analysis; Gastroenterology 2003 124: 47-56; Khuder et al. , Breast Cancer and NSAID Use: A Meta Analysis, British Journal of Cancer (2001) 84, 1188-1192. It is considered that COX-II may be important in certain types of cancer pathogenesis and animal studies suggest that long-term use of NSAIDs may prevent the development of these tumors. A promising solution to the problem of healing and avoiding upper gastrointestinal problems associated with NSAIDs, such as ulcers and dyspeptic symptoms in patients requiring continuous treatment with NSAIDs, is to combine the treatment of NSAIDs with an anti-ulcer drug tested for the healing and / or prophylaxis of gastrointestinal side effects associated with NSAIDs such as prostaglandin analogues, H2 receptor antagonists and proton pump inhibitors ("PPIs = proton pump inhibitors"). Additionally, since many of the patients suffering from inflammatory disorders also suffer from disorders related to gastric acid, there is a need for useful pharmaceutical formulations to co-administer a proton pump inhibitor for the treatment of a gastric acid related disorder and a Non-steroidal anti-inflammatory drug, useful for the treatment of an inflammatory disorder. SUMMARY OF THE INVENTION Pharmaceutical compositions are provided herein include a) a therapeutically effective amount of at least one labile acid proton pump inhibitor, b) at least one buffering agent in an amount sufficient to increase the pH of the gastric fluid to a pH which prevents acid degradation of at least some of the proton pump inhibitor in the gastric fluid and c) a therapeutically effective amount of at least one non-steroidal anti-inflammatory drug. Methods for treating disorders related to gastric acids and treating inflammatory disorders in a subject are provided, using the pharmaceutical compositions of the present invention. Methods for preventing disorders related to gastric acid during long-term administration of NSAIDs in a subject are also provided for the purpose of reducing the risk of heart attack or certain types of cancers by administering the pharmaceutical compositions of the present invention. Proton pump inhibitors include, but are not limited to, omeprazole, hydroxymeprazole, esomeprazole, tenatoprazole, lansoprazole, pantoprazole, rabeprazole, dontoprazole, habeprazole, periprazol, ransoprazole, pariprazole, leminoprazole; or a free acid free base, salt, hydrate, ester, amide, enantiomer, isomer, tautomer, polymorph or pro-drug thereof. In one embodiment, the proton pump inhibitor is omeprazole or a free base, free acid, salt, hydrate, ester, amide, enantiomer, isomer, tautomer, polymorph or pro-drug thereof. Compositions can contain between about 5mgs to about 200mgs of proton pump inhibitor, specifically about 5mg, about 10mg, about 15mg, about 20mg, about 30mg, about 40mg, about 60mg, or about 80mg of the proton pump inhibitor. In alternate embodiments, the compositions may contain between about 250-3000 mg of the proton pump inhibitor. Non-steroidal anti-inflammatory drugs include, but are not limited to, aminoarylcarboxylic acid derivatives such as enfenamic acid, etofenamate, flufenamic acid, isonixin, meclofenamic acid, mefenamic acid, niflumic acid, talniflute ato, terofenamate and tolfenamic acid, arylacetic acid derivatives as aceclofenac, acemetacin, alclofenac, amfenac, amtolmetin guacil, bromfenac, bufexamac, cinmetacin, clopirac, diclofenac sodium, etodolac, felbinac, fenclozic acid, fentiazac, glucametacin, ibufenac, indomethacin, isofezolac isoxepac, lonazolac, metyazinic acid, mofezolac, oxametacin, pirazolac, proglumetacin, sulindac, thiaramide, tolmetin, tropesin, and zomepirac; arylbutyric acid derivatives such as bumadizon, butibufen, fenbufen, xenbucin; arylcarboxylic acids such as clidanac, ketorolac, tinoridine; arylpropionic acid derivatives such as alminoprofen, benoxaprofin, bermoprofen, bucloxic acid, carprofen, fenoprofen, flunoxaprofen, flurbiprofen, ibuprofen, ibuproxam, indoprofen, ketoprofen, loxoprofen, naproxen, oxaprozin, piketoprofin, pirprofen, pranoprofen, protizinic acid, suprofen, tiaprofenic acid , ximoprofen, and zaltoprofen; pyrazoles such as diphenamizole and epirozole; pyrazolones such as apazone, benzpiperilon, feprazone, mofebutazone, morazone, oxifenbutazone, phenylbutazone, pipebuzone, propifenazone, prostaglandins, ramifenazone, suxibuzone, and thiazolinobutazone; salicylic acid derivatives such as acetaminosalol, aspirin, benorilate, bromosaligenin, calcium acetylsalicylate, diflunisai, ethersalate, fendosal, gentisic acid, glycosalicylate, imidazole salicylate, lysine acetylsalicylate, mesalamine, morpholine salicylate, 1-naphtyl salicylate, olsalazine, parsalmide, phenyl acetylsalicylate, phenyl salicylate, salacetamide, ida o-acetic salicylic acid, salicylsulfuric acid, salsalate, sulfalazine; fiazincarboxamides such as ampiroxicam, droxicam, isoxicam, lomoxicam, piroxicam, and tenoxicam, cyclooxygenase-II inhibitors ("COX-II") such as Celecoxib, Vioxx, Relafen, Lodine, and Voltaren; and others such as epsilon-acetamidocaproic acid, s-adenosylmethionine, 3-amino-4-hydroxybutyric acid, amixitrinin, bendazac, benzidamine, a-bisabolol, bucololome, diphenpyramide, ditazole, emorfazone, fepradinol, guaiazulene, nabumetone, nimesulide, oxaceprol, paraniline, perisoxal, proquazone, tenidap and zilenton. Compositions are provided such that the initial concentration in the serum of the proton pump inhibitor is greater than about 0.1 μg / ml at any time within about 30 minutes after the formulation is administered. Initial serum concentration of the proton pump inhibitor can be greater than about 0.1 μg / ml at any time within about 15 minutes. Initial concentration in the serum of the proton pump inhibitor can be greater than about 0.2 μg / ml at any time within about 1 hour after administration, greater than about 0.3 μg / ml at any time within about 45 minutes after administration . Compositions are provided such that a serum concentration greater than about 0.1 μg / ml can be maintained from at least about 30 minutes to about 1 hour after administration of the composition. Compositions are provided such that a serum concentration of the proton pump inhibitor greater than about 0.1 μg / ml can be maintained from at least about 15 minutes to about 30 minutes. Compositions are provided such that a serum concentration greater than about 0.1 μg / ml can be maintained from at least about 30 minutes to about 45 minutes. Compositions are provided such that a serum concentration greater than about 0.25 μg / ml can be maintained from at least about 30 minutes to about 1 hour. Compositions are provided such that a serum concentration greater than about 0.25 μg / ml can be maintained from at least about 30 minutes to about 45 minutes. Compositions are provided such that a serum concentration greater than about 0.25 μg / ml can be maintained from at least about 15 minutes to about 30 minutes. Compositions of the invention can be administered in an amount to maintain a serum concentration of the proton pump inhibitor, greater than about 0.15 μg / ml from about 15 minutes to about 1 hour after administration. Compositions can be administered of the invention in an amount to maintain a serum concentration of the proton pump inhubber greater than about 0.15 μg / ml from about 15 minutes to about 1.5 hours after administration. Compositions of the invention may be administered in an amount to maintain a serum concentration of the proton pump inhibitor greater than about 0.1 μg / ml from about 15 minutes to about 1.5 hours after administration. The compositions of the invention may be administered in an amount to maintain a serum concentration of the proton pump inhibitor greater than about 0.15 μg / ml from about 10 minutes to about 30 minutes after administration. Compositions of the invention may be administered in an amount to achieve an initial serum concentration of the proton pump inhibitor greater than about 0.15 μg / ml at any time from about 5 minutes to about 30 minutes after administration. Compositions of the invention can be administered in an amount to achieve an initial serum concentration of the proton pump inhibitor greater than about 0.15 μg / ml at any time within about 15 minutes after administration. Compositions are provided where, upon oral administration to the subject, the composition provides a pharmacokinetic profile such that at least about 50% of the total area under the time curve versus serum concentration (AUC = area under serum concentration time curve) for the protons, occurs within about 2 lyoras after administration of a single dose of the composition to the subject. Compositions are provided wherein, upon oral administration to the subject, the area under the time curve versus serum concentration (AUC) for the proton pump inhibitor in the first 2 hours, is at least about 60% the total area. Compositions are provided wherein the area under the time curve versus serum concentration (AUC) for the proton pump inhibitor in the first 2 hours is at least about 70% of the total area. Compositions are provided wherein at least about 50% of the total area under the time curve versus serum concentration (AUC) for the proton pump inhibitor, occurs within about 1.75 hours after administration of a single dose of the composition to the subject. Compositions are provided wherein at least about 50% of the total area under the time curve versus serum concentration (AUC) for the proton pump inhibitor occurs within about 1.5 hours after administration of a single dose of the composition to the subject. Compositions are provided wherein at least about 50% of the total area under the time curve versus serum concentration (AUC) for the proton pump inhibitor occurs within about 1 hour after administration of a single dose of the composition to the subject. Compositions are provided wherein, upon oral administration to the subject, the composition provides a pharmacokinetic profile such that the proton pump inhibitor reaches a maximum serum concentration within about 1 hour after administration of a single dose of the drug. composition. Compositions are provided wherein the maximum serum concentration is reached within about 45 minutes after administration of the composition. Compositions are provided wherein the maximum serum concentration is reached within about 30 minutes after administration of the composition. Compositions are provided wherein at least some of the proton pump inhibitor is microencapsulated, with a material that improves the shelf life of the pharmaceutical composition. Compositions are provided wherein at least some of the non-steroidal anti-inflammatory drug is micro-encapsulated with a material that improves the shelf life of the pharmaceutical composition. Compositions are provided wherein some of the proton pump inhibitor and some of the non-steroidal anti-inflammatory drug are micro-encapsulated with a material that improves the shelf life of the pharmaceutical composition. Materials that improve the shelf life of the pharmaceutical composition include but are not limited to cellulose hydroxypropyl ethers, low substituted hydroxypropyl ethers, cellulose hydroxypropyl methyl ethers, methyl cellulose polymers, ethyl celluloses and mixtures thereof, polyvinyl alcohol, hydroxyethyl celluloses, carboxymethyl celluloses, salts of carboxymethylcelluloses, polyvinyl alcohol, polyethylene glycol copolymers, monoglycerides, triglycerides, polyethylene glycols, modified food starch, acrylic polymers, blends of acrylic polymers with cellulose ethers, cellulose acetate phthalate, sepifilms, cyclodextrins; and its mixtures. The cellulose-hydroxypropyl ether may be, but is not limited to, Klucel ™ or NissoHPC. Cellulose-hydroxypropyl methyl ether may be, but is not limited to, Seppifilm-LC, Pharmacoat ™, Metolose SR, Opadry YS, PrimaFlo, BenecelMP824, or BenecelMP843. The mixture of methylcellulose and polymers of hydroxypropyl methylcellulose can be, but is not limited to Methocel ™, Benecel-MC, or Metolose ™. The ethylcellulose or its mixture can be but is not limited to Ethocel ™, Benecel ™ 043, Celacal, Cumibak NC, and E461. The polyvinyl alcohol may be, but is not limited to Opadry AMB. Acrylic polymers or mixtures thereof include, but are not limited to, Eudragits ™ EPO, Eudragits ™ RD100, and Eudragits ™ E 100. Other materials that improve the shelf life of the pharmaceutical composition include, but are not limited to, Natrosol ™, Aqualon ™ -CMC, and Kollicoat IRM. The material which improves the shelf life of the pharmaceutical composition may also include other compatible materials such as an antioxidant, a plasticizer, a buffering agent and mixtures thereof. Compositions are provided which include (a) a therapeutically effective amount of at least one labile acid proton pump inhibitor, wherein at least some of the proton pump inhibitor is coated, (b) at least one buffering agent in a sufficient amount to increase the pH of gastric fluid, to a pH value that prevents acid degradation of at least some of the proton pump inhibitor in the gastric fluid, and (c) a therapeutically effective amount of at least one anti-inflammatory drug is not steroidal, where the non-steroidal anti-inflammatory drug is useful for treating an inflammatory disorder. Inflammatory diseases include, but are not limited to, reperfusion injury to an ischemic organ (eg reperfusion injury to the ischemic myocardium), myocardial infarction, inflammatory bowel disease, rheumatoid arthritis, osteoarthritis, psoriasis, rejection of organ transplantation, inflammation of the ear, eye, throat, nose or skin, organ preservation, male or female sexual dysfunction, radiation-induced injury, asthma, respiratory disorder, metastasis, influenza, incontinence, attack, burn, trauma, acute pancreatitis, pyelonephritis, hepatitis, a autoimmune disease, an immune disorder, senile dementia, insulin-dependent diebates mellitus, disseminated intravascular coagulation, fat embolism, Alzheimer's disease, adult or infant respiratory disease, carcinogenesis in a neonate, hemorrhage in a neonate, restenosis, atherogenesis, angina ( particularly chest or chronic angina, stable), ischemic disease, congestive heart failure or pulmonary edema associated with acute myocardial infarction, thrombosis, hypertension (especially hypertension associated with cardiovascular surgical procedures), platelet aggregation, platelet adhesion, smooth muscle cell proliferation, vascular complications associated with use of medical devices, wounds associated with the use of medical devices, cerebrovascular ischemic events and the like. Compositions are provided which include (a) a therapeutically effective amount of at least one labile acid proton pump inhibitor, wherein at least some of the proton pump inhibitor, (b) at least one buffering agent in an amount sufficient to increase the pH of gastric fluid at a pH value which prevents acidic degradation of at least some of the proton pump inhibitor in the gastric fluid, (c) a therapeutically effective amount of at least one non-steroidal anti-inflammatory drug and (d) at least one thickening agent, wherein the dosage form is a powder for suspension. In some embodiments, the powder for suspension is substantially uniform or creates a substantially uniform suspension when mixed. Compositions are provided which include (a) a therapeutically effective amount of at least one labile acid proton pump inhibitor wherein at least some of the inhibitor of the proton pump inhibitor is microencapsulated, (b) at least one buffering agent in an amount sufficient to increase the pH of the gastric fluid to a value that prevents acid degradation of at least some of the proton pump inhibitor in the gastric fluid, (c) a therapeutically effective amount of at least one non-steroidal anti-inflammatory drug; and (d) at least one thickening agent wherein the dosage form is a powder for suspension. In some embodiments, the powder for suspension is substantially uniform or creates a substantially uniform suspension when mixed. Compositions are provided which include (a) a therapeutically effective amount of at least one labile acid proton pump inhibitor, (b) at least one buffering agent in an amount sufficient to increase the pH of the gastric fluid to a pH value that avoids the acid degradation of at least some of the proton pump inhibitor in the gastric fluid, (c) a therapeutically effective amount of at least one non-steroidal anti-inflammatory drug wherein at least some of the non-steroidal anti-inflammatory drug is coated , and (d) at least one thickening agent, wherein the dosage form is a powder for suspension. In some embodiments, the powder for suspension is substantially uniform. Compositions including (a) a therapeutically effective amount of at least one labile acid proton pump inhibitor, (b) at least one buffering agent in an amount sufficient to increase the pH of the gastric fluid to a pH that prevents acidic degradation of the at least some of the proton pump inhibitor in the gastric fluid, and (c) a therapeutically effective amount of at least one non-steroidal anti-inflammatory drug, wherein the compositions are free of sucralfate as set forth herein. Compositions are provided which include (a) a therapeutically effective amount of at least one labile acid proton pump inhibitor wherein at least some of the proton pump inhibitor is coated, (b) at least one buffering agent in an amount sufficient to increasing the pH of the gastric fluid at pH which prevents acid degradation of at least some of the proton pump inhibitor in the gastric fluid, and (c) a therapeutically effective amount of at least one non-steroidal anti-inflammatory drug, wherein the Proton pump inhibitor is useful for treating a disorder related to gastric acid and the non-steroidal anti-inflammatory drug is useful for treating an inflammatory disorder or other disease treatable by a non-steroidal anti-inflammatory drug. Compositions are provided which include (a) a therapeutically effective amount of at least one labile acid proton pump inhibitor, (b) at least one buffering agent in an amount sufficient to increase the pH of the gastric fluid at a pH that prevents degradation. acid of at least some of the proton pump inhibitor in the gastric fluid, and (c) a therapeutically effective amount of at least one non-steroidal anti-inflammatory drug, wherein the nonsteroidal anti-inflammatory drug is useful in decreasing the risk of attack to the heart. Compositions are provided which include (a) a therapeutically effective amount of at least one labile acid proton pump inhibitor, (b) at least one buffering agent in an amount sufficient to increase the pH of the gastric fluid at a pH that prevents degradation. acid of at least some of the proton pump inhibitor in the gastric fluid, and (c) a therapeutically effective amount of at least one non-steroidal anti-inflammatory drug, wherein the pharmaceutical composition is useful to prevent cancer. Compositions are provided which include (a) a therapeutically effective amount of at least one labile acid proton pump inhibitor, (b) at least one buffering agent in an amount sufficient to increase the pH of the gastric fluid at a pH that prevents degradation. acid of at least some of the proton pump inhibitor in the gastric fluid, and (c) a therapeutically effective amount of at least one non-steroidal anti-inflammatory drug, wherein the non-steroidal anti-inflammatory drug is a COX-II inhibitor. Compositions including (a) a therapeutically effective amount of at least one labile acid proton pump inhibitor, (b) at least one buffering agent in an amount sufficient to increase the pH of the gastric fluid to a pH that prevents acidic degradation of the at least some of the proton pump inhibitor in the gastric fluid, and (c) a therapeutically effective amount of at least one non-steroidal anti-inflammatory drug, wherein the buffering agent is an alkaline earth metal salt or a group IA metal selected from bicarbonate salt of a metal of group IA, a carbonate salt of a metal of group IA. The buffering agent can be, but is not limited to, an amino acid, an alkali metal salt of an amino acid, aluminum hydroxide, co-precipitated aluminum hydroxide / magnesium carbonate / calcium carbonate, aluminum magnesium hydroxide, -precipitated aluminum hydroxide / magnesium hydroxide, coprecipitated aluminum hydroxide / sodium bicarbonate, aluminum glycinate, calcium acetate, calcium bicarbonate, calcium borate, calcium carbonate, calcium citrate, calcium gluconate, glycerophosphate calcium, calcium hydroxide, calcium lactate, calcium phthalate, calcium phosphate, calcium succinate, calcium tartrate, dibasic sodium phosphate, dipotassium hydrogen phosphate, dipotassium phosphate, disodium hydrogen phosphate, disodium hydroxide, sodium hydroxide dry aluminum, L-arginine, magnesium acetate, magnesium aluminate, magnesium borate, magnesium bicarbonate, magnesium carbonate, magnesium citrate, glyco Magnesium nate, Magnesium hydroxide, Magnesium lactate, Magnesium aluminate metasilicate, Magnesium oxide, Magnesium phthalate, Magnesium phosphate, Magnesium silicate, Magnesium succinate. magnesium tartrate, potassium acetate, potassium carbonate, potassium bicarbonate, potassium borate, potassium citrate, potassium metaphosphate, potassium phthalate, potassium phosphate, potassium polyphosphate, potassium pyrophosphate, potassium succinate, tartrate potassium, sodium acetate, sodium bicarbonate, sodium borate, sodium carbonate, sodium citrate, sodium gluconate, sodium hydrogen phosphate, sodium hydroxide, sodium lactate, sodium phthalate, sodium phosphate, sodium polyphosphate , sodium pyrophosphate, sodium sesquicarbonate, sodium succinate, sodium tartrate, sodium tripolyphosphate, synthetic hydrotalcite, tetrapotassium pyrophosphate, tetrasodium pyrophosphate, tripotassium phosphate, trisodium phosphate, trometamol and their mixtures. In particular, the buffering agent can be sodium bicarbonate, sodium carbonate, calcium carbonate, magnesium oxide, magnesium hydroxide, magnesium carbonate, aluminum hydroxide and mixtures thereof. Compositions as described above are provided, wherein the ratio of buffer to proton pump inhibitor is at least 10: 1; 12: 1; 15: 1; 20: 1; 22: 1; 25: 1; 30: 1; 35: 1; and 40: 1. Compositions as described above are provided, wherein the buffering agent is sodium bicarbonate and is present at about 0.1 mEq / mg of proton pump inhibitor at about 5 mEq / mg of proton pump inhibitor. Compositions are provided as described herein, wherein the buffering agent is a mixture of sodium bicarbonate and magnesium hydroxide and each buffering agent is present at about 0.1 mEq / mg of proton pump inhibitor at about 5 mEq / mg inhibitor of proton pump. Compositions are provided as described herein, wherein the buffering agent is a mixture of sodium bicarbonate, calcium carbonate and magnesium hydroxide and each buffering agent is present at about 0.1 mEq / mg of proton pump inhibitor at about 5mEq / mg of proton pump inhibitor. Compositions are provided as described herein, wherein the buffering agent is present in an amount of about 0.1 mEq / mg of about 5 mEq / mg of the proton pump inhibitor, or about 0.5 mEq / mg of at about 3 mEq / mg of the proton pump inhibitor, or about 0.8 mEq / mg of at about 2.5 mEq / mg of the proton pump inhibitor, or about 0.9mEq / mg of at about 2.0 mEq / mg of the proton pump inhibitor , or about 0.9 mEq / mg of at about 1.8 mEq / mg of the proton pump inhibitor. Compositions are provided as described herein, wherein the buffering agent is present in an amount of at least 1.0 mEq / mg of at about 1.5 mEq / mg of the proton pump inhibitor, or at least 0.5 mEq / mg of the inhibitor of proton pump. Compositions are provided as described herein, including about 200 to 3000 mg of the buffering agent, or about 500 to about 2500 mg of the buffering agent, or about 1000 to about 2000 mg of the buffering agent, or about 1500 to about 2000 mg. of the buffering agent. Compositions including (a) a therapeutically effective amount of at least one labile acid proton pump inhibitor, (b) at least one buffering agent in an amount sufficient to increase the pH of the gastric fluid at a pH that prevents acidic degradation of the at least some of the proton pump inhibitor in the gastric fluid, and (c) a therapeutically effective amount of at least one non-steroidal anti-inflammatory drug is provided, wherein at least some of the nonsteroidal anti-inflammatory drug is coated. Convenient coatings include but are not limited to, gastric resistance coatings such as enteric coatings, controlled release coatings, enzyme control coatings, film coatings, sustained release coatings, immediate release coatings, and delayed release coatings. Also provided are compositions wherein the NSAID is a weakly acidic, lipid-soluble compound. Compositions are provided which include (a) a therapeutically effective amount of at least one labile acid proton pump inhibitor, (b) at least one buffering agent selected from sodium bicarbonate, calcium carbonate and magnesium hydroxide, wherein the agent buffer is present in an amount sufficient to increase the gastric fluid, and (c) a therapeutically effective amount of at least one non-steroidal anti-inflammatory drug. Compositions including (a) a therapeutically effective amount of at least one labile acid proton pump inhibitor, (b) at least one buffering agent in an amount sufficient to increase the pH of gastric fluid to a pH that prevents acidic degradation of at least some of the proton pump inhibitor in the gastric fluid, and (c) a therapeutically effective amount of at least one non-steroidal anti-inflammatory drug, wherein the composition is in a selected dosage form of a powder, a tablet , a bite-disintegrating tablet, a chewable tablet, a capsule, an effervescent powder, a rapidly disintegrating tablet or an aqueous suspension produced from powder. Compositions including (a) a therapeutically effective amount of at least one labile acid proton pump inhibitor, (b) at least one buffering agent in an amount sufficient to increase the pH of gastric fluid to a pH that prevents acidic degradation of at least some of the proton pump inhibitor in the gastric fluid, and (c) a therapeutically effective amount of at least one non-steroidal anti-inflammatory drug, wherein the composition is in the form of a tablet and the tablet consists of a first and second layers wherein the first layer comprises at least some of the non-steroidal anti-inflammatory drug and the second layer comprises at least some of the proton pump inhibitor and the buffering agent. Compositions are provided as described herein, which also include one or more excipients including but not limited to parietal cell activators, erosion facilitators, flavoring agents, sweetening agents, diffusion facilitators, antioxidants and carrier materials selected from binders, agents of suspension, disintegrating agents, fillers, surfactants, solubilizers, stabilizers, lubricants, wetting agents, diluents, anti-adherents, and anti-foaming agents. Methods for treating a gastric acid related disorder and treating an inflammatory disease are provided by administering to the subject a pharmaceutical composition comprising (a) a therapeutically effective amount of at least one labile acid proton pump inhibitor, (b) at least one buffering agent in an amount sufficient to increase the pH of gastric fluid to a pH which prevents acid degradation of at least some of the proton pump inhibitor in the gastric fluid, and (c) a therapeutically effective amount of at least one anti-inflammatory drug. Non-steroidal, where the proton pump inhibitor treats the disorder related to gastric acids and the non-steroidal anti-inflammatory drug treats the inflammatory disorder. Methods are provided wherein the composition as described above is formulated for delivery to the stomach of at least some of the proton pump inhibitor. Methods are provided wherein the composition as described herein is formulated for duodenal delivery of some of the proton pump inhibitor. Methods for treating a disorder related to gastric acid and treating an inflammatory disease when administering a horse are provided, a pharmaceutical composition that includes (a) a therapeutically effective amount of at least one labile acid proton pump inhibitor, (b) at least one buffering agent in an amount sufficient to increase the pH of gastric fluid at a pH that avoids acid degradation of at least some of the proton pump inhibitor in the gastric fluid, and (c) a therapeutically effective amount of at least one non-steroidal anti-inflammatory drug, wherein the proton pump inhibitor treats the gastric acid related disorder and the non-steroidal anti-inflammatory drug treats the inflammatory disorder. Methods for treating a disorder related to gastric acids are provided including but not limited to duodenal ulcer disease, gastric ulcer disease, gastroesophageal reflux disease, erosive esophagitis, symptomatic gastroesophageal reflux disease of poor response, pathological gastrointestinal hypersecretory disease, Zollinger Ellison, heartburn, esophageal disorder and acid dyspepsia. Methods are provided in which the proton pump inhibitor treats an episode of gastric acid-related disorder. Methods are provided wherein the proton pump inhibitor prevents or treats a gastric acid-related disorder induced by NSAIDs. Methods are provided wherein the proton pump inhibitor prevents or treats an NSAID-induced gastric acid related disorder, further wherein at least some of the NSAID is coated, optionally enteric coated. Methods are provided wherein the proton pump inhibitor prevents or treats an NSAID-induced gastric acid related disorder, further wherein at least some of the proton pump inhibitor is coated, optionally enteric coated. Methods are provided for treating an inflammatory disorder including, but not limited to, reperfusion injury to an ischemic organ such as reperfusion injury to ischemic myocardium, myocardial infarction, inflammatory bowel diseases, rheumatoid arthritis, osteoarthritis, psoriasis, transplant rejection of organ, inflammation of the ear, eye, throat, nose or skin, organ preservation, male or female sexual dysfunction, variation induced injury, asthma, respiratory disorder, metastasis, influenza, incontinence, stroke, burn, trauma, acute pancreatitis, pielonitritis, hepatitis, an autoimmune disease and immune disorder, senile dementia, insulin-dependent diabetes mellitus, disseminated intravascular coagulation, fat embolism, Alzheimer's disease, adult or child respiratory disorder, carcinogenesis in a neonate, hemorrhage in a neonate, restenosis , arteriogenesis, angina (including angina pec ho stable, chronic), ischemic disease, congestive heart failure or pulmonary edema associated with acute myocardial infarction, thrombosis, hypertension (including hypertension associated with cardiovascular surgical procedures), platelet aggregation, platelet adhesion, proliferation of smooth muscle cells, vascular complications associated with the use of medical devices, injuries associated with the use of medical devices, ischemic cerebrovascular events and the like. Methods for treating a gastric acid related disorder and decreasing the risk of a heart attack are provided by administering to the subject a pharmaceutical composition that includes (a) a therapeutically effective amount of at least one labile acid proton pump inhibitor, ( b) at least one buffering agent in an amount sufficient to increase the pH of gastric fluid to a pH that prevents acidic degradation of at least some of the proton pump inhibitor in the gastric fluid, and (c) a therapeutically effective amount of less a non-steroidal anti-inflammatory drug, where the proton pump inhibitor treats the gastric acid-related disorder and the non-steroidal anti-inflammatory drug decreases the risk of heart attack. Methods for treating a gastric acid related disorder and decreasing the risk of cancer are provided by administering to the subject a pharmaceutical composition that includes (a) a therapeutically effective amount of at least one labile acid proton pump inhibitor., (b) at least one buffering agent in an amount sufficient to increase the pH of gastric fluid to a pH that prevents acidic degradation of at least some of the proton pump inhibitor in the gastric fluid, and (c) a therapeutically effective amount of at least one non-steroidal anti-inflammatory drug, wherein the proton pump inhibitor treats the gastric acid-related disorder and the nonsteroidal anti-inflammatory drug decreases the risk of certain types of cancers including but not limited to esophageal cancer, lung cancer , colorectal cancer, breast cancer and prostate cancer. Methods for protecting against esophageal disorder or esophageal damage are provided by administering to the subject a pharmaceutical composition that includes (a) a therapeutically effective amount of at least one labile acid proton pump inhibitor, (b) at least one buffering agent in a sufficient amount to increase the pH of the gastric fluid to a pH that prevents acidic degradation of at least some of the proton pump inhibitor in the gastric fluid, and (c) a therapeutically effective amount of at least one non-steroidal anti-inflammatory drug. Methods for treating a gastric acid related disorder and treating inflammation, pain, or fever are provided by administering to the subject a pharmaceutical composition that includes (a) a therapeutically effective amount of at least one labile acid proton pump inhibitor, (b) ) at least one buffering agent in an amount sufficient to increase the pH of gastric fluid, at a pH that prevents acid degradation of at least some of the proton pump inhibitor in the gastric fluid, and (c) a therapeutically effective amount of at least one non-steroidal anti-inflammatory drug, wherein the proton pump inhibitor treats the gastric acid-related disorder and the nonsteroidal anti-inflammatory drug treats the subject's inflammation, pain or fever. Methods are provided wherein the non-steroidal anti-inflammatory drug is used to treat arthritis symptoms in a patient who requires it. Methods for treating a disorder related to gastric acids and treating an inflammatory disorder are provided by administering to a subject, a pharmaceutical composition that includes (a) a therapeutically effective amount of at least one labile acid proton pump inhibitor, (b) al minus a buffering agent in an amount sufficient to increase the pH of gastric fluid to a pH that prevents acidic degradation of at least some of the proton pump inhibitor in the gastric fluid, and (c) a therapeutically effective amount of at least one drug Non-steroidal anti-inflammatory, wherein the composition is in a dosage form that includes but is not limited to, a powder, a powder for suspension, a tablet, a coated tablet (brand, capsule-cablet = caplet), a tablet for disintegration by bite, a chewable tablet, a capsule, an effervescent powder, a fast disintegrating tablet, or an aqueous suspension produced from the dust Methods are provided, wherein the composition further comprises one or more excipients including, but not limited to, parietal cell activators, erosion facilitators, flavoring agents, sweetening agents, diffusion facilitators, antioxidants and carrier materials selected from binders, agents of suspension, disintegrating agents, fillers, surfactants, solubilizers, stabilizers, lubricants, wetting agents, diluents, anti-adherents, and anti-foaming agents. DETAILED DESCRIPTION OF THE INVENTION The present invention is directed to pharmaceutical compositions comprising a proton pump inhibitor, a buffering agent and a non-steroidal anti-inflammatory drug, wherein the compositions are useful for treating a disease, condition or disorder, in where the treatment includes treating the symptoms of a disease, condition or disorder. Methods for treatment using the pharmaceutical compositions of the present invention are also described. It has been discovered that pharmaceutical compositions comprising (1) a labile acid proton pump inhibitor, together with (2) one or more buffering agents and (3) a non-steroidal anti-inflammatory drug, provide relief from disorders related to gastric acids. and provide relief for inflammatory disorders in a subject. It has been discovered that pharmaceutical compositions comprising (1) a labile acid proton pump inhibitor, together with (2) one or more buffering agents, and (3) a non-steroidal anti-inflammatory drug, provide relief from acid-related disorders. gastric and reduces the risk of cardiovascular disease in a subject. It has been discovered that pharmaceutical compositions comprising (1) a labile acid proton pump inhibitor, together with (2) one or more buffering agents, and (3) a non-steroidal anti-inflammatory drug, provide relief from acid-related disorders. gastric and reduce the risk of cancer in a subject. It has been discovered that pharmaceutical compositions comprising (1) a labile acid proton pump inhibitor, which is microencapsulated with a material that improves the life / storage of the pharmaceutical composition, together with (2) one or more buffering agents, and (3) a non-steroidal anti-inflammatory drug, they provide superior performance by improving the stability of the storage life of the pharmaceutical composition during manufacture and storage. It has been found that pharmaceutical compositions comprising (1) a labile acid proton pump inhibitor, together with (2) one or more buffering agents, and (3) a non-steroidal anti-inflammatory drug, which is coated, provide superior performance by improving the storage life stability of the pharmaceutical composition during manufacture and storage. GLOSSARY To further facilitate an understanding of the invention and its preferred embodiments, the meaning of the terms used herein will be apparent from the context of this specification, in view of the common use of various terms and the explicit definitions of other terms which are provided in the following glossary or in the subsequent description. As used herein, the terms "comprises", "includes" and "as" are used in their broad, non-limiting sense. The term "approximately" is used in the form of a synonym with the term "approximate". Illustratively, the use of the term "approximate" indicates that values are slightly outside the quoted values, that is, more or less 0.1% to 10%, which is also effective and safe. These doses in this manner are encompassed by the scope of the claims which describe the terms "approximate" and "approximately". The phrase "labile acid pharmaceutical agent" refers to any pharmacologically active drug subject to acid catalyzed degradation. "anti-adherent", "slippery" or "anti-adhesion" agents, prevent the formulation components from adding or adhering and improving the flow characteristics of the material. These compounds include, for example, colloidal silicon dioxide, such as Cab-o-silMR.; tribasic calcium phosphate, talc, corn starch, DL-leucine, sodium lauryl sulfate, magnesium stearate, calcium stearate, sodium stearate, kaolin, and micronized amorphous silicon dioxide (Syloid ™) and the like. "Anti-foaming agents" reduce foaming during processing, which may result in coagulation of aqueous dispersions, bubbles in the finished film, or generally deteriorate processing. Exemplary anti-foaming agents include silicon emulsions or sorbitan sesquiolate. "Antioxidants" include, for example, butylated hydroxytoluene (BHT), sodium ascorbate, and tocopherol.

"Binders" impart cohesive qualities and include, for example, alginic acid, and its salts; cellulose derivatives such as carboxymethylcellulose, methylcellulose (for example Methocel ™), hydroxymethylpropylmethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose (for example Klucel ™), ethylcellulose (for example Ethocel ™), microcrystalline cellulose (for example Avicel ™); microcrystalline dextrose; amylose; magnesium aluminum silicate; polysaccharide acids; Bentonites; jelly; polyvinylpyrrolidone / vinyl aceate copolymer; crospovidone; povidone; starch; pregelatinized starch; tragacanth; dextrin; a sugar; such as sucrose (for example Dipac ™), glucose; dextrose; molasses; mannitol; sorbitol; xylitol (for example Xylitab ™), and lactose; a natural or synthetic gum such as acacia, tragacanth, ghatti gum, isapol shell mucilage, polyvinylpyrilidone (for example Polyvidone ™ CL, Kollidon ™ CL, Polyplasdone ™ XL-10), larch arabogalactan, Veegum ™, polyethylene glycol, waxes, sodium alginate and similar. "Bioavailability" refers to the proportion in which an active portion, eg, drug, prodrug or metabolite is absorbed into the circulation in general and the available site of action of the drug in the body is available.

"Carrier materials" include any excipients commonly used in pharmaceutical and should be selected based on compatibility with the proton pump inhibitor and the properties of the release profile of the desired dosage form. Exemplary carrier materials include, for example, binders, suspending agents, disintegrating agents, fillers, surfactants, solubilizers, stabilizers, lubricants, wetting agents, diluents and the like. "Pharmaceutically compatible carrier materials" may comprise, for example, acacia, gelatin, colloidal silicon dioxide, calcium glycerophosphate, calcium lactate, maltodextrin, glycerin, magnesium silicate, sodium caseinate, soy lecithin, sodium chloride, tricalcium phosphate. , dipotassium phosphate, sodium stearyl lactylate, caragenine, monoglyceride, diglyceride, pregelatinized starch, and the like. See, for example, Remington: The Science and Practice of Pharmacy, Nineteenth Ed (Easton, Pa .: Mack Publishing Company, 1995); Hoover, John E., Remington's Pharmaceutical Sciences, Mack Publishing Co. , Easton, Pennsylvania 1975; Liberman, H.A. and Lachman, L., Eds., Pharmaceutical Dosage Forms, Marcel Decker, New York, N.Y., 1980; and Pharmaceutical Dosage Forms and Drug Delivery Systems, Seventh Ed. (Lippincott Williams &Wiikins 1999). "Character notes" include, for example, aromatics, base flavors, and perception factors. The intensity of the character note can be adjusted in scales from 0-none, 1-light, 2-moderate, or 3-strong. A "derivative" is a compound that is produced from another compound of similar structure by the replacement of an atom, molecule or group substitution by another suitable atom, molecule or group. For example, one or more hydrogen atoms of a compound may be substituted by one or more alkyl, acyl, amino hydroxyl, halo, haloalkyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, or heteroalkyl group, to produce a derivative of this compound. "Diffusion facilitators" and "dispersing agents" include materials that control the diffusion of an aqueous fluid through a coating. Exemplary dispersing agents / diffusion facilitators include, for example, hydrophilic polymers, electrolytes, Tween ™ 60 or 80, PEG and the like. Combinations of one or more erosion facilitators, one or more diffusion facilitators may also be employed in the present invention. "Diluents" increase the volume of the composition to facilitate understanding. These compounds include, for example, lactose; starch; mannitol; sorbitol; dextrose; microcrystalline cellulose such as Avicel ™; dibasic calcium phosphate; calcium phosphate dihydrate; Tricalcium phosphate; calcium phosphate; anhydrous lactose; lactose dries by dew; pregelatinized starch; compressible sugar; such as Di-PacMR (Amstar); mannitol; hydroxypropylmethylcellulose; sucrose-based diluents; pastry sugar; monobasic calcium sulfate monohydrate; calcium sulfate dihydrate; calcium lactate trihydrate; Dextrates, hydrolyzed cereal solids; amylose; powdery cellulose; calcium carbonate; glycine; kaolin; mannitol; sodium chloride; inositol; bentonite; and similar. The term "disintegrate" includes both dissolution and dispersion of the dosage form when contacted with gastrointestinal fluid. "Disintegration agents" facilitate the decomposition or disintegration of substances. Examples of disintegrating agents include starch, for example a natural starch such as corn starch or potato starch, a pregelatinized starch such as National 1551 or Amijel ™, or sodium starch glycolate such as Promogel ™ or Explotab ™; a cellulose such as a wood product, methylcrystalline cellulose, for example, Avicel ™, Avicel ™ PH101, Avicel ™ PH102, Avicel ™ PH105, Elcema ™ PlOO, Emcocel ™, Vivacel ™, Ming Tia ™, and Solka-Floc ™, methylcellulose, croscalmellose, or an interlaced cellulose such as interlaced sodium carboxylmethylcellulose (Ac-Di ~ SolMR), crosslinked carboxylmethylcellulose or cross-linked croscarmellose; an interlaced starch such as sodium starch glycolate; an interlaced polymer such as crospovidone; an interlaced polyvinylpyrrolidone; alginate such as alginic acid or an alginic acid salt such as sodium alginate; a clay such as VeegumM HV (magnesium aluminum silicate); a gum such as agar, guar, algaroba, karaya, pectin or tragacanth; sodium starch glycolate; bentonite; a natural sponge; a surfactant; a resin such as a cation exchange resin; citrus pulp; sodium lauryl sulfate; Sodium lauryl sulfate in combination with starch, - and the like. "Drug absorption" or "absorption" refers to the process of movement from the site of administration of the drug into the systemic circulation, for example into the bloodstream of a subject. An "enteric coating" is a substance that remains substantially intact in the stomach, but dissolves and releases the drug once the small intestine is reached. In general, the enteric coating comprises a polymeric material which prevents release in the low pH environment of the stomach but which ionizes at a slightly higher pH, typically a pH of 4 or 5, and thus sufficiently dissolves in the intestine thin to gradually release the active agent there. "Erosion Facilitator" includes materials that control the erosion of a particular material in gastrointestinal fluid. Erosion facilitators are generally known by those with ordinary skill in the art. Exemplary erosion facilitators include, for example, hydrophilic polymers, electrolytes, proteins, peptides and amino acids. "Fillers" includes compounds such as lactose, calcium carbonate, calcium phosphates, dibasic calcium phosphate, calcium sulfate, microcrystalline cellulose, cellulose powder, dextrose; dextrations; dextran, starches, pregelatinized starch, sucrose, xylitol, lactitol, mannitol, sorbitol, sodium chloride, polyethylene glycol, and the like. "Flavoring agents" or "sweeteners" useful in the pharmaceutical compositions of the present invention include, for example, acacia syrup, acesulfame K, alitame, anise, apple, aspartame, banana, bavaria cream, berries, blackcurrant, caramel, mild flavor butter cloth, calcium citrate, camphor, caramel, cherry, cherry cream, chocolate, cinnamon, chewing gum, citrus, citrus punch, citrus cream, cotton candy, cocoa, cola, fresh cherry, cold citrus, cyclamate, cilamate, dextrose, eucalyptus, eugenol, fructose, fruit punch, ginger, glycyrrhite, liquorice syrup, grape, grapefruit, honey, isomalt, lemon, lime, lemon cream, monoammonium glycyrrhinate (Magnasweet ™), maltol, mannitol, maple, chocolate, menthol, mint cream, mixed cherry, neospiridine DC, neotame, orange, pear, peach, mint, mint cream, powder Prosweet ™, raspberry, root beer, rum, saccharin, safrole, sorbitol, spearmint, spearmint cream, strawberries, strawberry cream, stevia, sucralose, sucrose, saccharin sodium, saccharin, aspartame, acesulfame potassium, mannitol, etalim , silitol, sucralose, sorbitol, Swiss cream, tagatose, tangerine, thaumatin, tuti frutti, vanilla, walnut, watermelon, wild cherry, wintergreen, gilitol, or any combination of these flavoring ingredients, for example anise-menthol, cherry-anise, cinnamon-orange, cherry-cinnamon, chocolate-mint, lemon-honey, lemon-lime, lemon-mint, menthol-eucalyptus, orange-cream, vanilla-mint, and their mixtures. "Gastrointestinal fluid" is the fluid of stomach secretions of a subject or the saliva of a subject after oral administration of a composition of the present invention, or its equiv alent. A "stomach secretion equivalent" includes, for example, an in vitro fluid having similar content and / or pH as stomach secretions such as 1% sodium dodecyl sulfate solution or 0.1 N HCl solution in water. "Half-life" refers to the time required for the concentration of the drug in the plasma or the amount in the body to decrease to 50% of its maximum concentration. "Lubricants" are compounds that prevent, reduce or inhibit adhesion or friction of materials. Exemplary lubricants include, for example, steric acid; calcium hydroxide; talcum powder; sodium stearyl fumarate; a hydrocarbon such as mineral oil; hydrogenated vegetable oil such as hydrogenated soybean oil (Sterotex ™); higher fatty acids and their alkali metal or alkaline earth metal salts such as aluminum, calcium, magnesium, zinc, stearic acid, sodium stearate, glycerol, talc, waxes, Stearowet ™, boric acid, sodium benzoate, sodium acetate, sodium chloride, sodium, leucine, a polyethylene glycol or a methoxypolyethylene glycol such as CarbowaTMMR, sodium oleate, glyceryl behenate, polyethylene glycol, sodium or magnesium lauryl sulfate, colloidal silica, such as Syloid, Carb-0-SilMR a starch such as starch corn, silicone oil, a surfactant, and the like. A "measurable serum concentration" or "measurable plasma concentration" describes the concentration in the blood serum or blood plasma, typically measured in mg, μg, or ng of the therapeutic agent per ml, di, or 1. of blood serum, of a therapeutic agent, which is absorbed into the blood stream after administration. A person of ordinary skill in the art will be able to measure the serum concentration or plasma concentration of a proton pump individual or a non-steroidal anti-inflammatory drug, See, eg, Gonzalez H. et al., ". Chromatogr. B, Analyt, Technol Biomed, Life Sci., Vol 780, pp 459-65, (Nov. 25,2002). "Parietal cell activators" or "activators" stimulate the parietal cells and improve the inhibitor's pharmaceutical activity. Proton pump: Parietal cell activators include, for example, chocolate, alkaline substances such as sodium bicarbonate, calcium such as calcium carbonate, calcium gluconate, calcium hydroxide, calcium acetate and calcium glycerophosphate, peppermint oil; peppermint oil, coffee, tea and colas (even if they are decaffeinated), caffeine, theophylline, theobromine, amino acids (particularly aromatic amino acids such as phenylalanine and tryptophan), and combinations thereof. "Acodynamic" refers to the factors that determine the observed biological response to the concentration of the drug at the site of action. "Pharmacokinetics" refers to the factors that determine the achievement and maintenance of the appropriate concentration of the drug at the site of action. "Plasma concentration" refers to the concentration of a substance in the blood plasma or in the blood serum of a subject. It is understood that the plasma concentration of a therapeutic agent can vary many times between subjects, due to variability regarding the metabolism of therapeutic agents. In accordance with one aspect of the present invention, the plasma concentration of proton pump inhibitors and / or a non-steroidal anti-inflammatory drug can vary from subject to subject. Likewise, values such as the maximum plasma concentration (Cmax) or the time to reach the maximum serum concentration (Tmax) or the area under the time curve with serum concentration (AUC) may vary from subject to subject. Because of this variability, the amount needed to constitute "a therapeutically effective amount" of a proton pump inhibitor, non-steroidal anti-inflammatory drug or other therapeutic agent, may vary from subject to subject. It is understood that when average plasma concentrations are described for a population of subjects, these average values may include substantial variation. "Plasticizers" are compounds used to soften the micro-encapsulation material or film coating to make them less brittle. Suitable plasticizers include for example polyethylene glycols such as PEG 300, PEG 400, PEG 600, PEG 1450, PEG 3350, and PEG 800, stearic acid, propylene glycol, oleic acid, and triacetin. "Avoidance" or "prevention" when used in the context of a disorder related to gastric acid, does not mean the development of the gastrointestinal disorder or disease if it has not occurred, or without further development of gastrointestinal disorder or disease if there has already been development of the disorder. disorder or gastrointestinal disease. The ability to avoid some or all of the symptoms associated with the gastrointestinal disorder or disease is also considered. "Avoidance" or "prevention" when used in the context of an inflammatory disorder, means that there is no development of inflammatory disorder or disease if it has not yet occurred or there is no greater disorder or inflammatory disease if there has already been development of the inflammatory disorder. The ability to avoid some or all of the symptoms associated with the inflammatory disorder is also considered. A "prodrug" refers to a drug or compound in which the pharmacological action results from the conversion by metabolic processes within the body. Prodrugs are in general drug precursors that, after administration to a subject and subsequent absorption, are converted to an active or more active species by some process, such as conversion by a metabolic route. Some drugs have a chemical group present in the prodrug that makes it less active and / or confers solubility or some other property to the drug. Once the guimic group has been cleaved and / or modified from the prodrug, the active drug is generated. Prodrugs can be designed as reversible drug derivatives, to be used as modifiers to improve drug transport to site-specific tissues. The design of prodrugs to date has been to increase the effective water solubility of the therapeutic compound to target in regions where water is the main solvent. See for example Fedorak et al. , Am. J. Physio. 1, 269: G210-218 (1995); McLeod et al., Gastroenterol. , 106: 405-413 (1994); Hochhaus et al. , Biomed. Chrom. , 6: 283-286 (1992); J. Larsen and H. Bundgaard, Int. J Pharmaceut i, 37, 87 (1987); J. Larsen et al. , Int. J. Pharmaceutics, 47, 103 (1988); Sinkula et al. , J: Pharm. Sci. , 64: 181-210 (1975); T. Higuchi and V. Stella, Pro-drugs as Novel Delivery Systems, Vol. 14 of the A.C.S. Symposium Series; and Edward B. Roche, Bioreversible Carriers in Drug Design, American Pharmaceutical Association and Pergamon Press, 1987. "Serum concentration" refers to the concentration of a substance such as a therapeutic agent, in the blood plasma or in the serum of a subject's blood. It is understood that the concentration in the serum of a therapeutic agent can vary many times between subjects, due to variability regarding the metabolism of therapeutic agents. According to one aspect of the present invention, the serum concentration of a proton pump inhibitor and / or non-steroidal anti-inflammatory drug can vary from subject to subject. Likewise, values such as maximum serum concentration (Cmax) or time to reach maximum serum concentration (Tmax) or total area under the time curve versus serum concentration (AUC) may vary from subject to subject. Because of this variability, the amount needed to constitute "a therapeutically effective amount" of proton pump inhibitor, non-steroidal anti-inflammatory drug or other therapeutic agent, can vary from subject to subject. It is understood that when average serum concentrations are described for a population of subjects, these average values may include substantial variation. "Solubilizers" include compounds such as citric acid, succinic acid, fumaric acid, malic acid, tartaric acid, maleic acid, glutaric acid, sodium bicarbonate, sodium carbonate and the like. "Stabilizers" include compounds such as any antioxidant agents, buffers, acids and the like. "Suspending agents" or "thickening agents" include compounds such as polyvinylpyrrolidone, for example polyvinylpyrrolidone K12, polyvinylpyrrolidone K17, polyvinylpyrrolidone K25, or polyvinylpyrrolidone K30; polyethylene glycol, for example polyethylene glycol can have a molecular weight of from about 300 to about 6000, or about 3350 to about 4000, or about 7000 to about 5400; Sodium carboximethylcelulose; methylcellulose; hydroxypropylmethylcellulose; polysorbate-80; hydroxyethylcellulose; sodium alginate; gums such as, for example, gum tragacanth and acacia gum; guar gum; xanthans, including xanthan gums; sugars; cellulosics such as for example sodium carboxymethylcellulose, methylcellulose, sodium carboxymethylcellulose, hydroxypropylmethylcellulose, hydroxyethylcellulose; polysorbate-80; sodium alginate; polyethoxylated sorbitan monolaurate; polyethoxylated sorbitan monolaurate; povidone and similar. "Surfactants" include compounds such as sodium lauryl sulfate, sorbitan monooleate, polyoxyethylene sorbitan monooleate, polysorbates, poloxamers, bile salts, glyceryl monostearate, copolymers of ethylene glycol and propylene glycol, for example Pluronic ™ (BASF); and similar. A "therapeutically effective amount" or "effective amount" is a quantity of a pharmaceutical agent to achieve a pharmacological effect. The term "therapeutically effective amount" includes for example a prophylactically effective amount. An "effective amount" of a proton pump inhibitor is an amount effective to achieve a desired pharmacological effect or therapeutic improvement without undue adverse side effects. For example, an effective amount of a proton pump inhibitor refers to an amount of proton pump inhibitor that reduces acid secretion, or elevates the pH of gastrointestinal fluid, or reduces gastrointestinal bleeding or reduces the need for blood transfusion., or improves the survival rate, or provides a faster recovery from a disorder related to gastric acids. An "effective amount" of a non-steroidal anti-inflammatory drug is an amount effective to achieve a desired pharmacological effect on the condition of the subject, without inhibiting adverse side effects. The effective amount of a pharmaceutical agent will be chosen by those skilled in the art, depending on the particular patient and the level of disease. It is understood that "an effective amount" or "a therapeutically effective amount" may vary from subject to subject, due to the variation in metabolism of the therapeutic agents, such as proton pump inhibitors and / or non-steroidal anti-inflammatory agents, the age, weight, general condition of the subject, the condition to be treated, the severity of the condition to be treated and the judgment of the doctor who prescribed it. "Total aroma intensity" is the immediate immediate impression of the strength or concentration of the aroma and includes both aromatics and sensations perceived by the nose. "Total flavor intensity" is the immediate immediate impression of the strength or concentration of the flavor including aromatics, basic flavors and sensations perceived by the mouth. "Treat" or "treatment" as used in the context of a disorder related to gastric acids, refers to any treatment of a disorder or disease associated with a gastrointestinal disorder, such as avoiding disorder or disease that occurs in a subject may be predisposed to the disorder or disease, but has not yet been diagnosed as having the disorder or disease; slow the development of the disorder or disease, alleviate the disorder or disease, cause regression of the disorder or disease, alleviate a condition caused by the disease or disorder, or stop the symptoms of the disease or disorder. "Treat" or "treatment" as used in the context of an inflammatory disorder refers to any treatment of a disorder or disease associated with an inflammatory disorder, such as avoiding the disorder or disease that occurs in a subject who may be predisposed to disorder or illness, but has not yet been diagnosed as having the disorder or disease; inhibiting the disorder or disease, for example slowing down the development of the disorder or disease, alleviating the disorder or disease, causing regression of the disorder or disease, alleviating a condition caused by the disease or disorder, or stopping the symptoms of the disease or disorder. In this way, as used herein, the term "treat" is used synonymously with the term "avoid". "Wetting agents" include compounds such as oleic acid, glyceryl monostearate, sorbitan monooleate, sorbitan monolaurate, triethanolamine oleate, polyoxyethylene sorbitan monooleate, polyoxyethylene sorbitan monolaurate, sodium oleate, sodium lauryl sulfate, and the like. COMBINATION THERAPY Compositions and methods for combination therapy are provided here. According to one aspect, the pharmaceutical compositions described herein are used to treat a disorder related to gastric acids, wherein the treatment with a proton pump inhibitor is indicated, and to treat an inflammatory disorder wherein the treatment with an anti-drug -non-steroidal inflammatory is indicated. In one embodiment, pharmaceutical compositions described herein are used to treat a subject suffering from a disorder related to gastric acid and inflammation, pain or fever. In another embodiment, pharmaceutical compositions described herein are used to protect against an esophageal disorder or esophageal damage. In another embodiment, the pharmaceutical compositions described herein are used to treat a disorder related to gastric acids, wherein treatment with a proton pump inhibitor is indicated, and to decrease the risk of cardiovascular disease such as heart attack, or stroke. brain by administration of an appropriate non-steroidal anti-inflammatory drug. In still another embodiment, the pharmaceutical compositions described herein are used to treat a disorder related to gastric acids wherein treatment with a proton pump inhibitor is indicated, and to reduce the risk of certain types of cancer by administration of an anti-drug. -non-steroidal inflammation appropriate. Combination therapies contemplated by the present invention can be used as part of a specific treatment regimen intended to provide a beneficial effect for the co-action of the proton pump inhibitor and the non-steroidal anti-inflammatory drug. In one embodiment of the invention, the proton pump inhibitor is used to treat an inflammatory disorder induced by drugs. In another embodiment, the proton pump inhibitor and the non-steroidal anti-inflammatory agent are used to prevent cancer of the esophagus or upper gastrointestinal tracts. It is understood that the dosage regimen for treating, preventing or improving the condition or conditions for which relief is sought can be modified according to a variety of factors. These factors include the type of gastric acid disorder, and the inflammatory disorder of which the subject suffers, the proton pump inhibitor administered, the non-steroidal anti-inflammatory drug administered, as well as the age, weight, sex, diet and medical condition of the patient. subject. In this way, the dose regimen currently employed can vary widely and therefore may deviate from the dosage regimens set forth herein. According to one aspect, compositions and methods of the present invention are designed to produce release of the proton pump inhibitor to the delivery site, while avoiding or substantially inhibiting acidic degradation of the proton pump inhibitor. The present invention includes compositions and methods for treating, preventing, reversing, stopping or slowing the progression of a gastric acid-related disorder once it is clinically evident, or treating the symptoms associated with or related to the gastric acid related disorder, by administration to the subject of a composition of the present invention. The subject may already have a disorder related to gastric acid at the time of administration, or be at risk of developing a disorder related to gastric acids. The symptoms or conditions of a disorder related to gastric acid in a subject can be determined by a person skilled in the art and described in standard textbooks. The method comprises oral administration of an effective amount of one or more compositions of the present invention to a subject that requires it. Disorders related to gastric acids suitable for treatment or compositions and methods of the present invention include, but are not limited to, duodenal ulcer disease, gastrointestinal ulcer disease, gastroesophageal reflux disease (GERD), erosive esophagitis, symptomatic gastroesophageal reflux disease. of poor response, pathological gastrointestinal hypersecretory disease, Zollinger Ellison syndrome, heartburn, esophageal disorder and acid dyspepsia. According to another aspect, compositions and methods of the present invention are designed to deliver non-steroidal anti-inflammatory drugs to reduce inflammation, pain or fever in a patient. The present invention includes compositions and methods for treating inflammation or pain by administering to the subject a composition of the present invention. According to one aspect, compositions and methods for treating, preventing, reversing, stopping or slowing the progression of an inflammatory disorder once it becomes clinically evident, or treating symptoms associated with or related to the inflammatory disorder, by administering to the subject a composition of the present invention. The subject may already have an inflammatory disorder at the time of administration, or be at risk of developing an inflammatory disorder. The symptoms or conditions of an inflammatory disorder in a subject can be determined by a person skilled in the art and described in standard textbooks. The method comprises orally administering an effective amount of one or more compositions of the present invention to a subject that requires it. The effective amount of a non-steroidal anti-inflammatory agent may be a therapeutically effective amount or a prophylactically effective amount. Inflammatory disorders suitable for treatment using compositions and methods of the present invention include, but are not limited to, reperfusion injury to an ischemic organ (eg reperfusion injury to ischemic myocardium), myocardial infarction, inflammatory bowel disease, rheumatoid arthritis, osteoarthritis, psoriasis, organ transplant rejection, inflammation of the eye, ear, throat, nose or skin, organ observation, male or female sexual dysfunction, radiation induced injury, asthma, respiratory disorder, metastasis, influenza, incontinence, attack cerebral, heartburn, trauma, acute pancreatitis, pyelonephritis, hepatitis, an autoimmune disease, an immune disorder, senile dementia, insulin-dependent diabetes mellitus, disseminated intramuscular coagulation, fat embolism, Alzheimer's disease, adult or child respiratory disease, carcinogenesis in a neonate, hemorrhage in a neonate, restenosis, atherogenesis, angina, (for example chronic angina pectoris, stable) ischemic disease, congestive heart failure or pulmonary edema, associated with acute myocardial infarction, thrombosis, hypertension (for example hypertension associated with cardiovascular surgical procedures), platelet aggregation, platelet adhesion, smooth muscle cell proliferation, complications vascular diseases associated with the use of medical devices, injuries associated with the use of medical devices, cerebrovascular ischemic events and the like. According to one aspect, compositions and methods of the present invention are useful for treating a subject suffering from rheumatoid arthritis, osteoarthritis, high fever, familial adenomatous polyposis, acute or mild pain, or high fever. According to another aspect, compositions and methods of the present invention are useful to prevent heart attack in a subject at risk. According to another aspect, compositions and methods of the present invention are useful for decreasing the risk of an esophageal disorder or esophageal damage. According to one aspect, compositions and methods of the present invention are useful for treating a subject suffering from a disorder related to gastric acids and an inflammatory disorder. In one embodiment, compositions and methods of the present invention are used to treat an inflammatory disorder in a subject and to treat or prevent a drug-induced gastric acid related disorder. In another embodiment, compositions and methods of the present invention are used to treat a subject suffering from a disorder related to gastric acid and inflammation, pain or fever. For a particular subject, the most appropriate formulation or method of use of a composition of the present invention may depend on the type of gastric acid disorder and the period of time in which the proton pump inhibitor acts to treat the disorder related to gastric acid, as well as the type of inflammatory disorder and the period of time in which the non-steroidal anti-inflammatory drug treats the inflammatory disorder. A subject may suffer from a disorder related to gastric acid caused by the non-steroidal anti-inflammatory drug. Alternatively, a subject may suffer a disorder related to gastric acid that is not caused by or related to the non-steroidal anti-inflammatory drug. As described below, non-steroidal anti-inflammatory drugs useful for treating or preventing inflammatory disorders are known in the art and compositions of the present invention can be formulated to provide appropriate relief depending on the condition of the subject. According to one aspect of the invention, compositions and methods of the present invention are useful for treating a subject who suffers from an inflammatory disorder and a disorder related to gastric acids, which is not associated with the inflammatory disorder or treatment of the inflammatory disorder. Accordingly, compositions and methods of the present invention are useful for treating a subject who suffers from a disorder related to gastric acids and also suffers from an inflammatory disorder. Compositions of the present invention can be formulated to treat a disorder related to gastric acid and inflammatory disorder, according to one or both of the conditions for which relief is sought. As discussed below, proton pump inhibitors can be formulated to provide rapid relief as well as sustained relief of a gastric acid related disorder. As described below, nonsteroidal anti-inflammatory drugs can be formulated to be long lasting or provide rapid relief of the symptoms of an inflammatory disorder. In accordance with the methods of the invention, the formulation of the proton pump inhibitor is chosen based on the type of gastric acid related disorder suffered by the subject. According to the methods of the invention, the formulation of the non-steroidal anti-inflammatory drug is chosen based on the symptoms of the inflammatory disease in the suture. In one embodiment, a subject is administered a composition containing a proton pump inhibitor formulated to give rapid relief for an episode of gastric acid-related disorder, and a long-acting nonsteroidal anti-inflammatory drug. In another embodiment, a composition is administered to a subject which includes an uncoated proton pump inhibitor, formulated to provide rapid relief and coated proton pump inhibitor to prevent or treat recurrent episodes of the gastric acid related disorder, wherein the The composition also contains a long-lasting non-steroidal anti-inflammatory drug to treat inflammation or pain. In another aspect of the invention, a composition containing a proton pump inhibitor and a non-steroidal anti-inflammatory drug of long duration, wherein at least some of the long-acting nonsteroidal anti-inflammatory drug is administered to a subject. It is coated. In yet another aspect of the invention, a composition containing a proton pump inhibitor and a nonsteroidal antiinflammatory drug of prolonged action is administered to a subject, wherein at least some of the non-steroidal anti-inflammatory drug of prolonged duration is coated with an immediate release coating to improve the shelf life of the pharmaceutical composition. According to another aspect of the invention, a composition containing a proton pump inhibitor and a non-steroidal anti-inflammatory drug of prolonged action is administered to a subject, wherein at least some of the non-steroidal anti-inflammatory drug of Prolonged duration is coated with an enteric coating that is designed for delayed release of the non-steroidal anti-inflammatory drug. The pharmaceutical agents that constitute the combination therapy described herein can be a combined dose form or in a separate dosage form intended for substantially simultaneous administration. The pharmaceutical agents that constitute the combination therapy can also be administered sequentially, with any therapeutic compound that is administered by a regimen that requires two-step administration. The two-step administration regimen may require sequential administration of the active agents or spaced administration of the separate active agents. The period of time between the multiple administration steps may be in the range of a few minutes to several hours, depending on the properties of each pharmaceutical agent, such as potency, solubility, bioavailability, plasma half-life and kinetic profile of the pharmaceutical agent. . The circadian variation of the target molecule concentration can also determine the optimal dose range. The compositions and methods described herein can also be used in conjunction with other well-known therapeutic reagents, which are chosen for their particular utility against the condition being treated. In general, the compositions described herein and in embodiments wherein combination therapy is employed, other agents do not have to be administered in the same pharmaceutical composition, and may, due to different physical and chemical characteristics, require to be administered by different routes. The determination of the mode of administration and the advisability of the administration when possible, in the same pharmaceutical composition, is well within the knowledge of the person with skill in the specialty. The initial administration can be carried out according to established protocols known in the art, and then, based on the observed effects, the doses, modes of administration and administration times can be modified by the physician with skill in the art. The selection of the particular compounds used, it will depend on the diagnosis of the doctors in charge and their judgment of the patient's condition and the appropriate treatment protocol. The compounds can be administered concurrently (for example simultaneously, essentially simultaneously or within the same treatment protocol) or sequentially, depending on the nature of the proliferative disease, the condition of the patient and the current selection of the compounds employed. The determination of the order of administration and the number of administration repetitions of each therapeutic agent during a treatment protocol is well within the knowledge of the physician with skill in the specialty after evaluation of the disease to be treated and the condition of the patient. PROTON PUMP INHIBITORS The terms "proton pump inhibitor", "PPI", and "proton pump inhibiting agent" can be used interchangeably to distribute any labile acid pharmaceutical agent that possesses pharmacological activity as an H + inhibitor. / K + -ATPasa. A proton pump inhibitor may, if desired be in a free base form, free acid, salt, ester, hydrate, anhydrate, amide, enantiomer, isomer, tautomer, prodrug, polymorph, derivative or the like provided the base free, salt, ester, hydrate, amide, enantiomer, isomer, tautomer, prodrug or any other pharmacologically convenient derivative is therapeutically active. In various embodiments, the proton pump inhibitor can be a substituted bicyclic aryl imidazole, wherein the aryl group can be for example a pyridine, a phenyl, or a pyrimidine group and is connected at positions 4 and 5 of the imidazole ring . Proton pump inhibitors comprising a substituted bicyclic aryl imidazole include but are not limited to omeprazole, hydroxyomeprazole, esomeprazole, lansoprazole, pantoprazole, rabeprazole, dontoprazole, habeprazole, perprazole, tenatoprazole, ransoprazole, pariprazole, leminoprazole, or a free base, acid free, salt, hydrate, ester, amide, enantiomer, isomer, tautomer, polymorph, prodrug or its derivative. See for example The Merck Index, Merck &; Co. Rahway, N. J. (2001). Other proton pump inhibitors include but are not limited to soraprazan (Altana); ilaprazole (U.S. Patent Number 5,703,097) (Il-Yang); AZD- 0865 (AstraZeneca); YH-1885 (PCT publication WO 96/05177) (SB-641257) (2-pyrimidinamine, 4- (3,4-dihydro-methyl-2 (1H) -isoquinolinyl-N-4-fluorophenyl-5, 6-dimethyl monohydrochloride) (YuHan); BY-112 (Altana); SPI-447 (Imidazo (1, 2-a) thieno (3, 2-c) pyridin-3-amine, 5-methyl-2- (2-methyl-3-thienyl) (Shinnippon); 3-hydroxymethyl-2-methyl- 9-phenyl-7H-8,9-dihydro-pyran (2,3-c) -imidazo (1,2-a) pyridine (PCT publication number WO 95/27714) (AstraZeneca); Pharmaprojects No. 4950 (3 -hydroxymethyl-2-methyl-9-phenyl-7H-8, 9-dihydro-pyran (2,3-c) -imidazo (1, 2-a) pyridine) (AstraZeneca, ceased) WO 95/27714; Pharmaprojects No 4891 (EP700899) (Aventis); Pharmaprojects No. 4697 PCT Publication WO 95/32959) (AstraZeneca); H-335/25 (AstraZeneca); T-330 (Saitama 335) (Pharmacological Research Lab); Pharmaprojects No. 3177 (Roche); BY-574 (Altana); Pharmaprojects No. 2870 (Pfizer); AU-1421 (EP 264883) (Merck); AU-2064 (Merck); AY-28200 (Wyeth); Pharmaprojects No. 2126 (Aventis); WY-26769 (Wyeth); pumaprazole (PCT publication WO 96/05199) (Altana); YH-1238 (YuHan); Pharmaprojects No. 5648 (PCT publication number WO 97/32854) (Dainippon); BY-686 (Altana); YM-020 (Yamanouchi); GYKI-34655 (Ivax); FPL-65372 (Aventis); Pharmaprojects No. 3264 (EP 509974) (AstraZeneca); nepaprazol (Toa Eiyo); HN-11203 (Nycomed Pharma); OPC-22575; pumilacidin A (BMS); saviprazol (EP234485) (Aventis); SKandF-95601 (GSK, discontinuous)); Pharmaprojects No. 2522 (EP 204215) (Pfizer); S-3337 (Aventis); RS-13232A (Roche); AU-1363 (Merck); SKandF-96067 (EP 259174) (Altana); SUN8176 (Daiichi Phama); Ro- 18-5362 (Roche); ufiprazol (EP 74341) (AstraZeneca); and Bay-p-1455 (Bayer); or a free base, free acid, acid, hydrate, ester, amide, enantiomer, isomer, tautomer, polymorph, prodrug or derivative of these compounds. Still other proton pump inhibitors contemplated by the present invention include those described in the following U.S. Patents. Nos. 4,628,098; 4,689,333; 4,786,505; 4,853,230 4,965,269; 5,021,433; 5,026,560; 5,045,321; 5,093,132 5,430,042; 5,433,959; 5,576,025; 5,639,478; 5,703,110 5,705,517; 5,708,017; 5,731,006; 5,824,339; 5,855,914 5,879,708; 5,948,773; 6,017,560; 6,123,962; 6,187,340 6,296,875; 6,319,904; 6,328,994; 4,255,431; 4,508,905 4,636,499; 4,738,974; 5,690,960; 5,714,504; 5,753,265 5,817,338; 6,093,734; 6,013,281; 6,136,344; 6,183,776 6,328,994; 6,479,075; 6,559,167. Other substituted bicyclic aryl imidazole compounds as well as their salts, hydrates, esters, amides, enantiomers, isomers, tautomers, polymorphs, prodrugs, and derivatives, can be prepared using standard procedures known to those skilled in the art of organic synthesis chemistry.

See, for example, March, Advanced Organic Chemistry: Reactions, Mechanisms and Structure, 4th Ed. (New York: Wiley-Interscience, 1992); Leonard et al. , Advanced Practical Organic Chemistry (1992); Howarth et al. , Core Orcjrartic Chemistry (1998); and Weisermel et al. , Industrial Organic Chemistry (2002). "Pharmaceutically acceptable salts" or "salts" include for example the salt of a proton pump inhibitor prepared from formic, acetic, propionic, succinic, glycolic, gluconic, lactic, malic, tartaric, citric, ascorbic, glucuronic acids. , maleic, fumaric, pyruvic, aspartic, glutamic, benzoic, anthranilic, silylic, stearic, salicylic, p-hydroxybenzoic, phenylacetic, mandelic, embonic, methanesulfonic, ethanesulfonic, benzenesulfonic, pantothenic, toluenesulfonic, 2-hydroxyethane sulfonic, sulphanilic, cyclohexylaminosulfonic, algenic , hydroxybutyric, galactárico and galacturónico. In one embodiment, acid addition salts are prepared from the free base using conventional methodology involving reaction of the free base with a convenient acid. Suitable acids for preparing acid addition salts include both organic acids, for example acetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, malic acid, malonic acid, succinic acid, maleic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid , ethanesulfonic acid, p-toluenesulfonic acid, salicylic acid, and the like as well as inorganic acids for example hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid and the like. In other embodiments, an acid addition salt is reconverted to the free base by treatment with a convenient base. In a further embodiment, the acid addition salts of the proton pump inhibitors are halide salts, which are prepared using hydrochloric or hydrobromic acids. In still other embodiments, the basic salts are alkali metal salts, for example sodium salt and copper salt. Salt forms of the proton pump inhibitors include, but are not limited to: a sodium salt form such as esomeprazole sodium, omeprazole sodium, rabeprazole sodium, pantoprazole sodium; or a magnesium salt form such as esomeprazole magnesium or omeprazole magnesium, described in U.S. Pat. number 5,900,424; a calcium salt form; or a potassium salt form such as the potassium salt of esomeprazole, described in U.S. patent application. No. 02/0198239 and in the US patent. number 6,511,996. Other salts of esomeprazole are described in E.U.A. 4,738,974 and E.U.A. 6,369,085. Salt forms of pantoprazole and lansoprazole are discussed in U.S. Pat. numbers 4,758,579 and 4,628,098, respectively. In one embodiment, the preparation of esters involves the functionalization of hydroxyl and / or carboxyl groups that may be present within the molecular structure of the drug. In one embodiment, the esters are acyl-substituted derivatives of free alcohol groups, for example, portions derived from carboxylic acids of the formula RCOOR-L wherein x is a lower alkyl group. Esters can be reconverted to free acids if desired using conventional procedures such as hydrogenolysis or hydrolysis. "Amides" can be prepared using techniques known to those skilled in the art or described in the relevant literature. For example, amides can be prepared from esters, using convenient amine reagents or they can be prepared from anhydride or acid chloride by reaction with an amine group such as ammonia or a lower alkyl-amine. "Tautomers" of substituted bicyclic aryl imidazoles include for example omeprazole tautomers such as those described in U.S. Pat. Nos. 6,262,085; 6,262,086; 6,268,385; 6,312,723; 6,316,020; 6,326,384; 6,369,087; and 6,444,689; and the patent publication of the US. number 02/0156103. An exemplary "isomer" of a substituted bicyclic aryl imidazole is the isomer of omeprazole including but not limited to isomers described in Oishi et al., Acta Cryst. (1989), C45, 1921-1923; U.S. Patent 6,150,380; patent publication of the U.S. number 02/0156284; and PCT publication number WO02 / 085889. Exemplary "polymorphs" include but are not limited to those described in PCT publication number W092 / 08716, and US patents. numbers 4, 045,563; 4,182,766 4,508,905 4,628,098 4,636,499 4,689,333; 4,758,579 4,783,974 4,786,505 4,808,596 4,853,230; 5,026,560 5,013,743 5,035,899 5,045,321 5, 045,552; 5,093,132 5,093,342 5,433,959 5,464,632 5,536,735; 5,576,025 5,599,794 5,629,305 5,639,478 5,690,960; 5,703,110 5,705,517 5,714,504 5, 731, 006 5, 879, 708; 5,900,424 5,948,773 5,997,903 6,017,560 6,123,962; 6,147,103 6,150,380 6,166,213 6,191,148 5,187,340; 6,268,385 6,262, 086 6,262, 085 6,296, 875 6,316,020; 6,328,994 6,326,384 6,369,085 6,369,087 6,380,234; 6,428,810; 6,444,689; and 6,462.0577 MICRONIZED PROTON PUMP INHIBITOR The particle size of the proton pump inhibitor can accept the solid dose form in different ways. Since the decreased particle size increases in surface area (S), the reduction in particle size provides an increase in dissolution rate (dM / dt) as expressed in the following Noyes-Whitney equation: dM / dt = dS / h (Cs-C) M = mass of the drug dissolved; t = time; D = diffusion coefficient of the drug; S = effective surface area of the drug particles; H = stationary layer thickness; Cs = concentration of solution at saturation; and C = concentration of solution at time t. Because omeprazole, as well as other proton pump inhibitors, have poor water solubility, to assist in the rapid absorption of the drug product, various embodiments of the present invention of micronized proton pump inhibitor are used in the formulation of the drug product. In some embodiments, the average particle size is at least about 90% of the micronized proton pump inhibitor is less than about 40 μm, or less than about 35 μm or less than about 30 μm, or less than about 25 μm, or less than about 20 μm, or less than about 15 μm, or less than about 10 μm. In other embodiments, at least 80% of the micronized proton pump inhibitor has an average particle size less than about 40 μm, or less than about 35 μm, or less than about 30 μm, or less than about 25 μm, or less at about 20 μm, or less than about 15 μm, or less than about 10 μm. In still other embodiments, at least 70% of the micronized proton pump inhibitor has an average particle size of less than about 40 μm, or less than about 35 μm, or less than about 30 μm, or less than about 25 μm, or less than about 20 μm, or less than about 15 μm, or less than about 10 μm. Compositions are provided wherein the micronized proton pump inhibitor is of a size that allows much more than 75% of the proton pump inhibitor to be released within 1 hour or within about 50 minutes, or within about 40 minutes, or within approximately 30 minutes, or within approximately 20 minutes, or within approximately 10 minutes, or within approximately 5 minutes of the dissolution test. In another embodiment of the invention, the micronized proton pump inhibitor is of a size that allows more than 90% of the proton pump inhibitor to be released within about 1 hour, or within about 50 minutes, or within about 40 minutes, or within approximately 30 minutes, or within approximately 20 minutes, or within approximately 10 minutes, or within approximately 5 minutes of the dissolution test. See Provisional Patent Application of the U.S.A. serial number 60 / 488,324 filed July 18, 2003, which is incorporated herein by reference in its entirety. SHOCK ABSORBING AGENTS The pharmaceutical composition of the invention comprises one or more buffers. A class of buffer agents useful in the present invention includes, but is not limited to, buffering agents that possess pharmacological activity as a weak base or as a strong base. In a modality, the buffering agent, when formulated or supplied with a proton pump inhibiting agent, functions to substantially prevent or inhibit the acid degradation of the proton pump degrader by gastrointestinal fluid for a period of time, for example for a period of time sufficient to preserve the bioavailability of the administered proton pump inhibitor. The damping agent can be supplied before, during and / or after the delivery of the proton pump inhibitor. In one aspect of the present invention, the buffering agent includes a salt of a metal of group IA (alkali metal), including for example a carbonate salt and a metal of group IA, a carbonate salt of a metal of group IA; a buffering agent of an alkaline earth metal (metal of group IIA); an aluminum buffering agent; a calcium buffering agent; or a magnesium buffering agent. Other buffering agents suitable for the present invention include, for example, carbonates, phosphates, bicarbonates, citrates, borates, acetates, phthalates, tartrates, succinates and the like of alkali metal (Group IA metal including but not limited to lithium, sodium, potassium, rubido, cesium and francium) or alkaline earth metal (metal of group IIA including but not limited to beryllium, magnesium, calcium, strontium, barium, radium), such as phosphate, citrate, borate, acetate, bicarbonate and sodium or potassium carbonate. In various embodiments, a buffering agent includes an amino acid, an alkali metal salt of amino acid, aluminum hydroxide, coprecipitated aluminum hydroxide / magnesium carbonate / calcium carbonate, aluminum magnesium hydroxide, coprecipitated aluminum hydroxide / hydroxide of magnesium, coprecipitate of aluminum hydroxide / sodium bicarbonate, aluminum glycinate, calcium acetate, calcium bicarbonate, calcium borate, calcium carbonate, calcium citrate, calcium gluconate, calcium glycerophosphate, calcium hydroxide, lactate calcium, calcium phthalate, calcium phosphate, calcium succinate, calcium tartrate, dibasic sodium phosphate, potassium dihydrogen phosphate, potassium dihydrogen phosphate, sodium dihydrogen phosphate, sulfinate di sodium, dry aluminum hydroxide gel, L- arginine, magnesium acetate, magnesium aluminate, magnesium borate, magnesium bicarbonate, magnesium carbonate, magnesium citrate, gluconate m agnesium, magnesium hydroxide, magnesium lactate, magnesium aluminate metasilicate, magnesium oxide, magnesium phthalate, magnesium phosphate, magnesium silicate, magnesium succinate, magnesium tartrate, potassium acetate, potassium carbonate, potassium bicarbonate , potassium borate, potassium acetate, potassium metaphosphate, potassium phthalate, potassium phosphate, potassium polyphosphate, potassium pyrophosphate, potassium succinate, potassium tartrate, sodium acetate, sodium bicarbonate, sodium borate, carbonate sodium, sodium citrate, sodium gluconate, sodium hydrogen phosphate, sodium hydroxide, sodium lactate, sodium phthalate, sodium phosphate, sodium polyphosphate, sodium pyrophosphate, sodium sesquicarbonate, sodium succinate, tartrate sodium, sodium tripolyphosphate, synthetic hydrotalcite, tetrapotassium pyrophosphate, tetrasodium pyrophosphate, tripotassium phosphate, trisodium phosphate and trometamol (see for example lists to be The Merck Index, Merck & Co. Rahway, N.J. (2001)). Certain proteins or protein hydrolysates that rapidly neutralize acids can serve as buffering agents in the present invention. Combinations of the aforementioned buffering agents can be employed in the pharmaceutical compositions described herein. Buffering agents useful in the present invention also include buffering agents or combinations of buffering agents that interact with HCl (or other acids in the environment of interest) faster than the proton pump inhibitor interacts with the same acids. When placed in the liquid phase, such as water, these buffering agents produce and maintain a higher pH than the pKa of the proton pump inhibitor.

In various embodiments, the buffering agent is selected from sodium bicarbonate, sodium carbonate, calcium carbonate, magnesium oxide, magnesium hydroxide, magnesium carbonate, aluminum hydroxide and mixtures thereof. In another embodiment, the buffering agent is sodium bicarbonate and is present from about 0.1 mEq / mg of the proton pump inhibitor to about 5 mEq / mg of the proton pump inhibitor. In yet another embodiment, the buffering agent is a mixture of sodium bicarbonate and magnesium hydroxide, wherein the sodium bicarbonate and magnesium hydroxide are present in the present 0.1 mEq / mg of the proton pump inhibitor up to about 5 mEq / mg of the proton pump inhibitor. In yet another embodiment, the buffering agent is a mixture of at least two buffering agents selected from sodium bicarbonate, calcium carbonate and magnesium hydroxide, wherein each buffer is present at approximately 0.1 mEq / mg of the proton pump inhibitor. to about 5 mEq / mg of the proton pump inhibitor. Compositions are provided as described herein, wherein the buffering agent is present in an amount of about 0.1 mEq / mg up to about 5 mEq / mg of the proton pump inhibitor, or about 0.25 mEq / mg of at about 3 mEq / mg of the proton pump inhibitor or about 0.3 mEq / mg of at about 2.5 mEq / mg of the proton pump inhibitor or about 0.4 mEq / mg of at about 2.0 mEq / mg of the proton pump inhibitor or about 0.5 mEq / mg of at about 1.5 mEq / mg of the proton pump inhibitor. Compositions are provided as described herein, wherein the buffering agent is present in an amount of at least 0.25 mEq / mg of at about 2.5 mEq / mg of the proton pump inhibitor or at least about 0.4 mEq / mg of the proton pump inhibitor. In one aspect of the invention, compositions are provided wherein the buffering agent is present in the pharmaceutical compositions of the present invention in an amount of about 1 mEq to about 160 mEq per dose, or about 5 mEq, or about 10 mEq, or about 11 mEq, or about 15 mEq, or about 19 mEq, or about 20 mEq, or about 22 mEq, or about 23 mEq, or about 24 mEq, or about 25 mEq, or about 30 mEq, or about 31 mEq, or about 35 mEg, or about 40 mEg, or about 45 mEg, or about 50 mEg, or about 60 mEg, or about 70 mEg, or about 80 mEq, or about 90 mEq, or about 100 mEq, or about 110 mEq, or about 120 mEq, or about 130 mEq, or about 140 mEq, or about 150 mEq, or about 160 mEq per dose. In another aspect of the invention, compositions are provided wherein the buffering agent is present in the composition on a weight to weight (w / w) basis greater than about 5 times, or more than about 10 times, or more than about 20 times , or more than about 30 times, or more than about 40 times, or more than about 50 times, or more than about 60 times, or more than about 70 times, or more than about 80 times, or more than about 90 times, or more than about 100 times the amount of the proton pump inhibiting agent. In another aspect of the invention, compositions are provided wherein the amount of buffering agent present in the pharmaceutical composition is between 200 and 3500 mg. In some embodiments, the amount of buffering agent present in the pharmaceutical composition is about 200 mg, or about 300 mg, or about 400 mg, or about 500 mg, or about 600 mg, or about 700 mg, or about 800 mg, or about 900 mg, or about 1000 mg, or about 1100 mg, or about 1200 mg, or about 1300 mg, or about 1400 mg, or of about 1500 mg, or about 1600 mg, or about 1700 mg, or about 1800 mg, or about 1900 mg, or about 2000 mg, or about 2100 mg, or about 2200 mg, or about 2300 mg, or approximately 2400 mg, or approximately 2500 mg, or approximately 2600 mg, or approximately 2700 mg, or approximately 2800 mg, or approximately 2900 mg, or approximately 3000 mg, or approximately 3100 mg , or approximately 3200 mg, or approximately 3500 mg. NSAIDS Non-steroidal anti-inflammatory drugs are useful in the treatment of inflammatory disorders. As used herein, "inflammatory disorder" includes, for example, reperfusion injury to an ischemic organ (eg reperfusion injury to the ischemic myocardium), myocardial infarction, inflammatory bowel disease, rheumatoid arthritis, osteoarthritis, psoriasis, rejection of organ transplantation. , inflammation of the ear, eye, throat, nose or skin, organ preservation, male or female sexual dysfunction, radiation induced injury, asthma, respiratory disorder, metastasis, influenza, incontinence, stroke, burn, trauma, acute pancreatitis, pyelonephritis, hepatitis, an autoimmune disease and immune disorder, senile dementia, insulin-dependent diabetes mellitus, disseminated intravascular coagulation, fat embolism, Alzheimer's disease, adult or infant respiratory disease, carcinogenesis in a neonate, hemorrhage in a neonate, restenosis, atherogenesis, angina (eg stable angina pectoris, chronic ica) ischemic disease, congestive heart failure or pulmonary edema associated with acute myocardial infarction, thrombosis, hypertension (eg hypertension associated with cardiovascular surgical procedures), platelet aggregation, platelet adhesion, smooth muscle cell proliferation, associated vascular complications with the use of medical devices, injuries associated with the use of medical devices, cerebrovascular and similar ischemic events.

In accordance with one aspect of the invention, compositions and methods are provided for alleviating symptoms of an inflammatory disorder. According to another aspect of the invention, compositions and methods are provided for treating or preventing an inflammatory disorder, including symptoms of the inflammatory disorder. In accordance with one aspect of the invention, compositions and methods are provided for treating or preventing an inflammatory disorder and for treating or preventing a drug-induced gastric related disorder. A "drug-induced related gastric disorder" includes gastric ulcers induced or associated with the use of medications such as NSAIDs including selective COX-II inhibitors and non-spheroidal anti-inflammatory drugs / nitric oxide donors (NO-NSAIDs). In accordance with another aspect of the invention, compositions and methods are provided for treating an inflammatory disorder and for treating a drug-induced gastric related disorder, wherein the drug-induced gastric disorder is the result of prolonged use of one or more drugs. non-steroidal anti-inflammatory drugs. Examples of suitable nonsteroidal anti-inflammatory drugs include but are not limited to aminoarylcarboxylic acid derivatives, such as enfenamic acid, etofenamate, flufenamic acid, isonixin, meclofenamic acid, mefenamic acid, niflumic acid, talniflumate, terofenamate, and tolfenamic acid; arylacetic acid derivatives such as aceclofenac, acemetacin, alclofenac, amfenac, amtolmetin guacil, bromfenac, bufexamac, cinmetacin, clopirac, diclofenac sodium, etodolac, felbinac, fenclozic acid, fentiazac, glucametacin, ibufenac, indomethacin, isofezolac isoxepac, lonazolac, metyazinic acid , mofezolac, oxametacin, pyrazolac, proglumetacin, sulindac, thiaramide, tolmetin, tropesin, and zomepirac; aryl butyl alcohol derivatives such as bumadizon, butibufen, fenbufen, xenbucin; arylcarboxylic acids such as clidanac, ketorolac, tinoridine; arylpropionic acid derivatives such as alminoprofen, benoxaprofin, bermoprofen, bucloxic acid, carprofen, fenoprofen, flunoxaprofen, flurbiprofen, ibuprofen, ibuproxam, indoprofen, ketoprofen, loxoprofen, naproxen, oxaprozin, piketoprofin, pirprofen, pranoprofen, protizinic acid, suprofen, tiaprofenic acid , ximoprofen, and zaltoprofen; pyrazoles such as diphenamizole, and epirozole; pyrazolones such as apazone, benzpiperilone, feprazone, mofebutazone, morazone, oxyphenbutazone, phenylbutazone, pipebuzone, propyphenazone, prostaglandin, ramifenazone, suxibuzone, and thiazolinobutazone; salicylic acid derivatives such as acetaminosalol, aspirin, benorilate, bromosaligenin, calcium acetylsalicylate, diflunisai, ethersalate, fendosal, gentisic acid, glycol salicylate, imidazole salicylate, lysine acetylsalicylate, mesalamine, morpholine salicylate, 1-naphthyl salicylate, olsalazine, parasalmide, phenyl acetylsalicylate, fhenyl salicylate, salacetamide, salicylamide o-acetic acid, salicylsulfuric acid, salsalate, sulfasalazine; thiazinecarboxamides such as amphyroxic, droxicam, isoxicam, lomoxicam, piroxicam, and tenoxicam; cyclooxygenase-II inhibitors ("COX-II") such as Celebrex (Celecoxib), Vioxx, Relafen, Lodine, and Voltaren and others, such as epsilon-acetamidocaproic acid, s-adenosylmethionine, 3-amino-4-hydroxybutyric acid, amixetrin, bendazac, benzidamine, bisabolol, bucololome, diphenpyramide, ditazole, emorfazone, fepradinol, guaiazulene, nabumetone, nimesulide, oxaceprol, paraniline, perisoxal, proquazone, tenidap and zilenton. Additionally, the non-steroidal anti-inflammatory drug can be a specific enantiomer of a non-steroidal anti-inflammatory drug. According to one aspect of the invention, compositions and methods that include long-acting nonsteroidal anti-inflammatory drugs such as naproxen sodium, flurbiprofen, ketoprofen, oxaprozin, indomethacin, cetoralac, nabumetone, mefenamic, piroxicam and COX-II inhibitors are useful . "prolonged duration or action" in relation to NSAIDs will mean a pharmacokinetic half-life of at least about 2 hours, at least about 4 hours and at least about 8 to 14 hours, wherein the duration of the action is equal to or exceeds approximately 6 to 8 hours. Exemplary extended-duration NSAIDs include: flurbiprofen with a half-life of approximately 6 hours; ketoprofen with a half-life of approximately 2 to 4 hours; naproxen and naproxen sodium with half-lives of approximately 12 to 15 hours and approximately 12 to 13 hours respectively; oxaprozin with half-life of approximately 42 to 50 hours; etodolac with half-life of approximately 7 hours; indomethacin with a half-life of approximately 4 to 6 hours, ketorolac with a half-life of approximately 8 to 9 hours; nabumetone with a half-life of approximately 22 to 30 hours; mefenamic acid with a half-life of approximately 4 hours; and piroxicam with a half-life of approximately 4 to 6 hours. Additionally, various NSAIDs that naturally do not have sufficient half-lives to be long-lasting can be formulated into nonsteroidal anti-inflammatory drugs of long duration. Methods for producing appropriate prolonged duration formulations are well known in the art. See for example Remington's Pharmaceutical Sciences, 16ch ed., A. Oslo editor, Easton, Pa. (1980); and Controlled Drug Delivery, Edith Mathiowitz, John Wiley & Sons (1999), ISBN: 0471148288. According to one aspect of the invention, it may also be useful to coat the non-steroidal anti-inflammatory drug. Suitable coatings include, but are not limited to, gastric resistant coatings such as enteric coatings (see for example W091 / 16895 and W091 / 16886), controlled release coatings, enzyme controlled coatings, film coatings, sustained release coatings, release coatings immediate and delayed release coatings. According to another aspect of the invention, it may be useful to formulate the NSAIDs in beads, granules, or coated pellets for delayed release. According to various aspects of the invention, the coating may be useful to improve the stability of the pharmaceutical compositions of the present invention or to allow a pharmaceutical release profile of the non-steroidal anti-inflammatory drug, useful for the successful treatment of a inflammatory disorder Commonly used NSAIDs The following table represents a partial state of NSAIDs suitable for the present invention. A person skilled in the art will understand that any NSAIDs that have been approved for use in a subject can be used in the compositions and methods of the present invention. Of course, the amount of NSAIDs currently administered to a subject will depend on the age, weight and general condition of the subject, the condition to be treated, the severity of the condition to be treated and the judgment of the prescribing physician. TABLE 1: REPRESENTATIVE NSAIDs AND THEIR EFFECTIVE DOSE * Drug Name Name Doses Effective Commercial Issues more than two or three times a day (for Voltaren or Cataflam) or 75 mgs twice a day (for Voltaren), - Voltaren-XR (prolonged release) 100 mgs once a day. Rheumatoid arthritis: 100-200 mgs per day; maximum daily dose of 225 mgs. Ankylosing spondylitis: 100-125 mgs per day. Pain and menstrual discomfort: 50 mgs every 8 hours; or an initial dose of 100 mgs followed by 2 doses of 50-mg of Etodolac Lodine; Lodine 200-400 mgs two Name of Drug Name Effective Commercial Doses Exemplary (Derived from XL three times a day; Acid 400-1200 mgs once Pirancarboxílico) per day; maximum daily dose of 1200 mgs.

Fenoprofen Nalfon 200-600 mgs. Flurbiprofen Oral Ansaid 300 mgs a day. (Derivative of Phenylalancic Acid) Ibuprofen Advil; Motrin; 200-800 mgs three a (Derived from Nuprin, four times a day, Propionic Acid) Genpril; My ol; Menadol maximum daily dose; of 1200 mgs. Haltran; Brufen Asprina Bayer; 50-1000 mgs per (Derived from Excedrin Dosage Salicylic Acid) Migraine; Astrix (enteric coating); Cartia (Duentric Drug Name Name Effective Commercial Dosages Ketoprofen Orudis; Oruvail 25-75 mgs three a (Derived four times a day; Acid 200 mgs once to the Arilacetic) day; maximum daily dose of 300 mgs.

Meclofenamate Meclomen 50-100 mgs every 4 to 6 Acid hours; daily anthranilic dose) maximum of 400 mgs.

Mobic Meloxicam 7.5-15 mgs once or (Derived from two a day, Oxicam dose) maximum daily of 15 mgs. Nabumetone Relafen 1000 mgs orally (Naftialcanone) once or twice a day; maximum daily dose of 2000 mgs.

Naproxen Sodium Anaprox; EC- Light pain a (Moderate Naprosyn Derivative, Menstrual Acid Pains, Arylacetic) Tendinitis and Acute Bursitis: 550 mgs followed by 275 mgs Drug Name Name Commercial Effective Doses Exemplary every 6 to 8 hours; 550 mgs every 12 hours; maximum daily dose of 1.375 mgs. Rheumatoid Arthritis, Osteoarthritis, and Anglilosante Spondylitis: 275-550 mgs twice a day. Acute drop: 825 mgs followed by 275 mgs every 8 hours. Naproxen Naprosyn; 250-500 mgs twice (Naproxyn XL acid, daily, 750-1000 mgs Arilacetic) Aleve; once a day; Maximum daily Naprelan dose of 1375 mgs. Colin - Trilisate Rheumatoid arthritis, Osteoarthritis trisalicylate, Magnesium more severe arthritis, (Salicylate) and shoulder with acute pain: 1500 mgs twice a day or 3,000 Drug Name Name Effective Dosage Commercial Dosages Nabumentone Relafen 1-2 grams per day.

Etodalac Ultradol 200-400 mgs once or twice a day. Floctafenin Idarac 200-400 mgs once or twice a day. Sulindac Clinoril 150-200 mgs twice (Derived from daily, Indeno daily dose) maximum of 400 mgs. Osteoarthritis: 200 mgs once a day or 100 mgs twice a day Rheumatoid Arthritis: 100-200 mgs twice a day. Acute Pain and Menstrual Pain: 400 mgs, followed by an additional 200 mgs if required on the first day. The subsequent days, 200 mgs twice a day.

Drug Name Name Effective Dosage Commercial Exemplary Familial Adenomatose Polyposis: 400 mgs twice a day. Tenoxicam Mobiflex, - Daily dose of 7.5- Tilcotil Tabs 20 mgs. Acid Surgam 300 mgs once or two Tiaprofénico a day. Mefenamic acid Ponstyl; Mefac; 500 mg as dose (Fenemato) Ponstan; initial followed by 250 mgs every 6 hours.

Diclofenac Diclofenac 100-200 mgs once or (Derived from two daily Acetic Benze Acid) Acetalofenac Arital 100 mgs once or two (Derived from daily Phenyl Acid Acid) Mornif lumato 750-1500 mgs (Niflumic Acid) daily in two or three doses. Diflunisai Dolobid Pain of light to (Salicylate) moderate: dose Name of Drug Name Effective Dosage Commercial Initial copies of 1,000 mgs followed by 500 milligrams every 8 to 12 hours; Maximum daily dose of 1,500 mgs. Osteoarthritis and Rheumatoid Arthritis: 250-500 mgs twice a day. Salsalato Disalcid 3000 mgs daily (Salicylate) divided in every 8-12 hours. Valdecoxib Bextra Osteoarthritis and (Rheumatoid Arthritis Inhibitor: COX-II) 10 mgs once a day. Painful menstruation: 20 mgs twice a day. Celecoxib Celebrex Osteoarthritis: 100 (Inhibitor of mgs once or twice to COX-II) day Name of Drug Name Effective Doses Commercial Exemplary Rheumatoid Arthritis: 200 mgs once or twice a day. Rofecoxib Vioxx Osteoarthritis: 12.5- (Inhibitor of 25 mgs once to COX-II) day. Acute Pain: 50 mgs once a day. * For other doses see any vademecum; the doses are oral unless otherwise indicated. STABILITY IMPROVERS Stability enhancers are described in the U.S. patent application. Serial number 10 / 893,203 filed on July 16, 2004, which is hereby incorporated by reference in its entirety. In accordance with one aspect of the present invention, the compositions may include microencapsulation of one or more of: the proton pump inhibitor; the non-steroidal anti-inflammatory drug; or the buffering agent, in order to improve the storage life of the composition. See provisional patent application of the U.S.A. Serial number 60/488 filed on July 18, 2003, which is fully incorporated by reference. Useful materials for improving the shelf life of the pharmaceutical compositions of the present invention include materials compatible with the proton pump inhibitor of pharmaceutical compositions that sufficiently isolate the proton pump inhibitor from other non-compatible excipients. Materials compatible with the proton pump inhibitors of the present invention are those which improve the storage life of the proton pump inhibitor, i.e. when braking or stopping the degradation of the proton pump inhibitor. Exemplary microencapsulation materials useful for improving the shelf life of pharmaceutical compositions comprising a proton pump inhibitor include but are not limited to: cellulose hydroxypropyl ethers (HCP) such as Klucel® or Nisso HPC; low substitution hydroxypropyl ethers (L-HPC); Cellulose Hydroxypropyl Methyl Ether (HPMC) such as Seppifilm-LC, Pharmacoat® (g), Metolose SR, Opadry YS, PrimaFlo, Benecel MP824, and Benecel MP843; methylcellulose polymers such as Methocel® and Metolose®; ethylcelluloses (EC) and their mixtures such as Ethocel®, Aqualon®-EC, Surelease®; polyvinyl alcohol (PVA) such as Opadry AMB; hydroxyethyl celluloses such as Natrosol®; carboxymethyl celluloses and salts of carboxymethyl celluloses (CMC) such as Aqualon®-CMC; copolymers of polyvinyl alcohol and polyethylene glycol such as Kollicoat IR®; monoglycerides (Myverol), triglycerides (KLX), polyethylene glycols, modified food starch, acrylic polymers and mixtures of acrylic polymers with cellulose ethers such as Eudragit® EPO, Eudragit® RD100, and Eudragit® ElOO; cellulose acetate phthalate; sepifilms, such as mixtures of HPMC and stearic acid, cyclodextrins; and mixtures of these materials. In various embodiments, a buffering agent such as sodium bicarbonate is incorporated into the microencapsulation material. In other embodiments, an antioxidant such as BHT is incorporated into the microencapsulation material. Still in other embodiments, plasticizers such as polyethylene glycols, for example, PEG 300, PEG 400, PEG 600, PEG 1450, PEG 3350, and PEG 800, stearic acid, propylene glycol, oleic acid and triacetin, are incorporated into the microencapsulation In other embodiments, the microencapsulation material useful for improving the shelf life of the pharmaceutical compositions is from USP or National Formulary (NF). In additional embodiments, one or more other compatible materials are present in the microencapsulation material. Exemplary materials include but are not limited to pH modifiers, parietal cell activatorsErosion facilitators, diffusion facilitators, antiadherents, antifoaming agents, antioxidants, flavoring agents and carrier materials such as binders, suspending agents, disintegrating agents, fillers, surfactants, solubilizers, stabilizers, lubricants, wetting agents and diluents. According to one aspect of the invention, the non-steroidal anti-inflammatory drug is coated. The coating can be for example a gastric resistance coating such as enteric coating (see for example W091 / 16895 and W091 / 16886), a controlled release coating, an enzymatic control coating, a film coating, a sustained release coating , an immediate release coating, or a delayed release coating. According to another aspect of the invention, the coating may be useful for improving the stability of the pharmaceutical compositions of the present invention. A pharmaceutical composition of the present invention can have an improved stability of shelf life if, for example, the proton pump inhibitor has less than about 0.5% degradation after one month of storage at room temperature, or less than about 1% of degradation after one month at room temperature, or less than about 1.5% degradation after one month of storage at room temperature, or less than about 2% degradation after one month of storage at room temperature, or less than about 2.5% degradation after one month of storage at room temperature, or less than about 3% degradation after one month of storage at room temperature. In other embodiments, a pharmaceutical composition of the present invention may have an improved storage life stability if the pharmaceutical composition contains less than about 5% of the total impurities after approximately 3 years of storage, or after approximately 2.5 years of storage. , or after approximately 2 years of storage, or after approximately 1.5 years of storage, or after approximately 1 year of storage, or after approximately 11 months of storage, or after approximately 10 months of storage, or after approximately 9 months of storage, or after approximately 8 months of storage, or after approximately 7 months of storage, or after approximately 6 months of storage, or after approximately 5 months of storage, or after approximately 4 months of storage, or after about 3 months of storage, or after 2 months of storage after 1 month of storage. In further embodiments, pharmaceutical compositions of the present invention can have an improved storage life stability if the pharmaceutical composition contains less degradation of the proton pump inhibitor than the proton pump inhibitor in the same formulation wherein the protons or the non-steroidal anti-inflammatory agent are not microencapsulated or the nonsteroidal anti-inflammatory drug is not coated, sometimes referred to as "naked". For example, if the proton pump inhibitor in the pharmaceutical composition degrades at room temperature of more than about 2% after one month of storage and the coated or microencapsulated material degrades at room temperature of less than about 2% after one month of storage, then the proton pump inhibitor has been microencapsulated with a compatible material that improves the shelf life of the pharmaceutical composition, or the non-steroidal anti-inflammatory drug has been coated with a compatible material that improves life in storage of the pharmaceutical composition. In some modalities, the pharmaceutical compositions have an increased storage life stability of at least about 5 days at room temperature, or at least about 10 days at room temperature, or at least about 15 days at room temperature, or at least about 20 days at room temperature environment, or at least about 25 days at room temperature, or at least about 30 days at room temperature, or at least about 2 months at room temperature, or at least about 3 months at room temperature, or at least about 4 months at room temperature environment, or at least about 5 months at room temperature, or at least about 6 months at room temperature, or at least about 7 months at room temperature, or at least about 8 months at room temperature, or at least about 9 months at room temperature environment, or at least about 10 months at room temperature, or at least about 11 months at room temperature, or at least about 1 year at room temperature, or at least about 1.5 years at room temperature, or at least about 2 years at room temperature, or at least about 2.5 years at room temperature, or about 3 years years at room temperature. In some embodiments of the present invention, the final formulation of the pharmaceutical composition will be in the form of a coated tablet or tablet and at least about 50%, or at least about 55%, or at least about 60%, or at least about 65%, or at least about 70%, or at least about 75%, or at least about 80%, or at least about 85%, or at least about 90%, or at least about 95%, or at least about 98%, or at least about 99% of the micro spheres survive the tabletting process, wherein the micro spheres that have survived the manufacturing process are those that provide the desired properties described herein. In other embodiments, the final formulation of the pharmaceutical composition is in the form of a powder for oral suspension and the microencapsulation material surrounding the proton pump inhibitor with the non-steroidal anti-inflammatory agent or the coating surrounding the agent Non-steroidal anti-inflammatory will dissolve enough in water, with or without agitation in less than an hour, or less than 50 minutes, or less than 40 minutes, or less than 30 minutes, or less than 25 minutes, or less than 20 minutes minutes, or less than 15 minutes, or less than 10 minutes, or less than 5 minutes, or less than 1 minute. "Dissolved enough" means that at least approximately of the encapsulation or coating material has dissolved. In various embodiments, the material useful for improving the shelf life of the pharmaceutical composition disintegrates sufficiently to release the proton pump inhibitor in the gastrointestinal fluid of the stomach in less than about 1.5 hours, or within about 10 minutes, or within approximately 20 minutes, or within approximately 30 minutes, or within approximately 40 minutes, or within approximately 50 minutes, or within approximately 1 hour, or within approximately 1.25 hours, or within approximately 1.5 hours after exposure to the gastrointestinal fluid. "Disintegrates enough" means that at least about 50% of the microencapsulation material has dissolved. MATERIALS THAT MASK THE TASTE Materials that mask taste or taste are described in the U.S. patent application. Serial Number 10 / 893,203 filed on July 16, 2004, which is hereby incorporated by reference in its entirety. According to another aspect, compositions and methods of the present invention may include materials that mask the taste to improve the taste of the composition. Proton pump inhibitors and some non-steroidal anti-inflammatory drugs have an inherently bitter taste. In an embodiment of the present invention, these bitter-tasting pharmaceuticals are microencapsulated with material that masks the taste. Useful materials for masking the taste of a pharmaceutical composition include those materials capable of microencapsulating the proton pump inhibitor and / or the non-steroidal anti-inflammatory drug, thereby protecting the senses from their bitter taste. Materials that mask the taste of the present invention provide superior pharmaceutical compositions for example by creating a more palatable pharmaceutical composition compared to pharmaceutical compositions without taste masking and / or by creating a dosage form that requires less of the traditional flavoring agents .

The "flavor leadership" criterion used to develop a palatable product includes 1) immediate impact of identification flavor, 2) rapid development of a full balanced flavor, 3) compatible oral perception factors, 4) no "unpleasant" tastes and 5) a short after taste. See for example: Worthington, A Matter of Taste, Pharmaceutical Executive (April 2001). The pharmaceutical compositions of the present invention improve upon one or more of these criteria. There are a number of known methods for determining the effect of a material that masks the taste, such as discrimination tests for differences between samples and for assigning in order a range to a series of samples of a specific characteristic; scale tests used to qualify the attributes of the specific product such as taste and appearance; expert tasters employed both to evaluate a specific sample quantitatively and qualitatively; affective tests either to measure the response between two products, measure the degree of liking or dislike of a specific product or attribute, or determine the appropriateness of a specific attribute; and descriptive methods used in flavor profiling to provide objective description of a product, are all methods used in the field. Different sensory qualities of a pharmaceutical composition such as aroma, flavor, character notes and after taste can be measured using tests known in the art. See Roy et al. , Modifying Biology: Mechanism, Ingredients, and Applications (1997). For example, the residual flavor of a product can be measured using a measure of time versus sensory intensity. Trials have been developed to alert a processor of bitter taste formulations of certain substances. Using information known to a person skilled in the art, it will be readily possible to determine whether one or more sensory qualities of the pharmaceutical composition of the present invention have been improved by the use of taste masking material. The taste of a pharmaceutical composition is important both to increase patient compliance and to compete with other commercialized products used for similar diseases, conditions and disorders. Taste, especially bitterness, is particularly important in pharmaceutical compositions for children since, because they can not weigh the positive result (improvement) against the immediate negative experience (the bitter taste in the mouth), they are more likely to refuse to take a drug that tastes bad. In this way, in pharmaceutical compositions for children, it becomes even more important to mask the bitter taste. The microencapsulation of the proton pump inhibitor can (1) reduce the amount of flavoring agents needed to create a palatable product and / or (2) mask the bitter taste of the proton pump inhibitor by separating the drug from the receptors of taste. Materials that mask taste or taste include, but are not limited to: cellulose hydroxypropyl ethers (HPC) such as Klucel® or Nisswo HPC; hydroxypropyl low substitution esters (L-HPC); cellulose hydroxypropyl methyl ethers (HPMC) such as Seppifilm-LC, Pharmacoat®, Metolose SR, Opadry YS, PrimaFlo, Benecel MP824, and Benecel MP843; methyl cellulose polymers such as Methocel® and Metolose®; ethyl celluloses (EC) and their mixtures such as E461, Ethocel®, Agualon®-EC, Surelease®; polyvinyl alcohol (PVA) such as Opadry AMB; hydroxyethyl celluloses such as Natrosol®; carboxymethyl celluloses and salts of carboxymethyl celluloses (CMC) such as Agualon®-CMC; polyvinyl alcohol and polyethylene glycol copolymers such as Kollicoat IR®; monoglycerides (Myverol), triglycerides (KLX), polyethylene glycols, modified food starch, acrylic polymers and blends of acrylic polymers with cellulose ethers such as Eudragit® EPO, Eudragit® RD100, and Eudragit® ElOO; cellulose acetate phthalate; sepifilms such as mixtures of HPMC and stearic acid, cyclodextrins and mixtures of these materials. In other embodiments of the present invention, additional taste masking materials contemplated are those described in U.S. Pat. numbers 4,851,226, 5,075,114, and 5,876,759. For additional examples of materials that mask taste, see for example Remington: The Science and Practice of Pharmacy, Nineteenth Ed. (Easton, Pa .: Mack Publishing Company, 1995); Hoover, John E., Remington's Pharmaceutical Sciences (Mack Publishing Co., Easton, Pennsylvania 1975); Liberman, H.A. and Lachman, L., Eds., Pharmaceutical Dosage Forms (Marcel Decker, New York, N.Y., 1980); and Pharmaceutical Dosage Forms and Drug Delivery Systems, Seventh Ed. (Lippincott Williams &Wiikins, 1999). In various embodiments, a buffering agent such as sodium bicarbonate is incorporated into the microencapsulation material. In other embodiments, an antioxidant such as BHT is incorporated into the microencapsulation material. Still in another embodiment, sodium chloride is incorporated into the material that masks the taste. Still in other embodiments, plasticizers such as polyethylene glycol and / or stearic acid are incorporated into the microencapsulation material. In further embodiments, one or more other compatible materials are present in the microencapsulation material. Exemplary materials include for example pH modifiers, parietal cell activators, erosion facilitators, diffusion facilitators, antiadherents, antifoaming agents, antioxidants, flavoring agents and carrier materials such as binders, suspending agents, disintegrating agents, fillers, surfactants. , solubilizers, stabilizers, lubricants, wetting agents, diluents. In addition to microencapsulating the proton pump inhibitors and / or the non-steroidal anti-inflammatory drug with a material that masks the taste as described herein, the pharmaceutical compositions of the present invention may also comprise one or more flavoring agents. "Flavoring agents" or "sweeteners" useful in the pharmaceutical compositions of the present invention include, for example acacia syrup, acesulfam K, alitame, anise, apple, aspartame, banana, Bavarian cream, berry, blackcurrant, caramel, mild flavor butter, calcium citrate, camphor, caramel, cherry, cherry cream, chocolate, cinnamon, chewing gum, citrus, citrus punch, citrus cream, sweet cotton, cocoa, cola, fresh cherry, fresh citrus, cyclamate, cilamate, dextrose , eucalyptus, eugenol, fructose, fruit punch, ginger, glycyrritinate, glycyrrhiza syrup (licorice), grape, grapefruit, honey, isomalt, lemon, lime, lemon cream, monoammonium glirrizinate (MagnaSweet®), maltol, mannitol, maple, marshmallow, menthol, mint cream, mixed berries, neo-speridine DC, neotame, orange, pear, peach, mint, mint cream, Prosweet® powder, raspberry, root beer, rum, saccharin, safrol, sorbitol, mint green, mint, cream, strawberry, c row of strawberry, stevia, sucralose, sucrose, saccharine sodium, saccharin, aspartame, acesulfame potassium, mannitol, talin, sucralose, sorbitol, Swiss cream, tagatose, tangerine, thaumatin, tutti frutti, vanilla, walnut, watermelon, wild cherry, wintergreen, xiglitol or any combination of these flavoring ingredients, for example anise-menthol, cherry-anise, cinnamon-orange, cherry-cinnamon, chocolate-mint, honey-lemon, lemon-lime, lemon-mint, menthol-eucalyptus, orange -cream, vanilla-mint and its mixtures. In other embodiments, sodium chloride is incorporated in the pharmaceutical composition. Based on the proton pump inhibitor, buffering agent and excipients as well as the amounts of each, a person skilled in the art will be able to determine the best flavor combination to provide the optimum taste product for the requirement and compliance by consumers. See, for example, Roy et al., Modifying Bitterness: Mechanism, Ingredients, and Applications (1997). In one embodiment, one or more flavoring agents are mixed with the taste masking material before microencapsulating the proton pump inhibitor and / or non-steroidal anti-inflammatory drug, and are therefore part of the taste masking material. In other embodiments, the flavoring agent is mixed with non-compatible excipients during the formulation process and therefore is not in contact with the proton pump inhibitor and / or the non-steroidal anti-inflammatory drug, and is not part of the material of microencapsulation. In another embodiment, a buffering agent, such as sodium bicarbonate, is also microencapsulated with one or more taste masking agents.

In another embodiment, the weight fraction of the material masking the taste for example is about 98% or less, about 95% or less, about 90% or less, about 85% or less, about 80% or less, about 75% or less, about 70% or less, about 65% or less, about 60% or less, about 55% or less, about 50% or less, about 45% or less, about 40% or less, about 35% or less , about 30% or less, about 25% or less, about 20% or less, about 15% or less, about 10% or less, about 5% or less, about 2%, or about 1% or less of the total weight of the pharmaceutical composition. In other embodiments of the present invention, the amount of flavoring agent necessary to create a palatable product, as compared to a pharmaceutical composition comprising proton pump inhibitor and / or the non-encapsulated nonsteroidal anti-inflammatory drug, is decreased at 5% or less, or 5 to 10%, or at 10 to 20%, or at 20 to 30%, or at 30 to 40%, or at 40 to 50%, or at 50 to 60%, or at 60 to 70%, or 70 to 80%, or 80 to 90%, or 90 to 95%, or greater than 95%. In still other embodiments, no flavoring agent is necessary to create a more palatable pharmaceutical composition, compared to a similar pharmaceutical composition comprising a proton pump inhibitor and / or non-steroidal anti-inflammatory drug not microencapsulated. In various embodiments of the invention, the total amount of flavoring agent present in the pharmaceutical composition is less than 20 grams, or less than 15 grams, or less than 10 grams, or less than 8 grams, or less than 5 grams, or less to 4 grams, or less than 3.5 grams, or less than 3 grams, or less than 2.5 grams, or less than 2 grams, or less than 1.5 grams, or less than 1 gram, or less than 500 mg, or less than 250 grams mg, or less than 150 mg, or less than 100 mg, or less than 50 mg. METHODS OF MICROENCAPSULATION The proton pump inhibitor, buffering agent and / or nonsteroidal anti-inflammatory drug can be microencapsulated by methods known to a person of ordinary skill in the art. These known methods include, for example, spray drying processes, solvent-spinning disc processes, hot melt processes, spray cooling methods, fluidized bed, electrostatic deposition, centrifugal extrusion, rotational suspension separation, polymerization in the liquid-gas or solid-gas interface, pressure extrusion, or an extraction bath with spray solvent. In addition to these, various chemical techniques for example complex coacervation, solvent evaporation, polymer-polymer incompatibility, interfacial polymerization of liquid medium, in situ polymerization, in-liquid drying, and desolvation in liquid medium, may also be employed. The centrifugal disc method allows: (1) an increased production rate adhered to higher feed rates and use of higher solids loading in the feed solution, (2) production of more spherical particles, (3) production of a more uniform coating and (4) limited plugging or sealing of the spray nozzle during the process. Spray drying is often more readily available for scaling up. In various embodiments, the material employed in the spray-drying encapsulation process is emulsified or dispersed in the core material in a concentrated form, for example 10 to 60% solids. The microencapsulation material in one embodiment is emulsified until approximately droplets of 1 to 3 m are obtained. Once a dispersion of proton pump inhibitor and encapsulating material is obtained, the emulsion is fed as droplets into the heated spray-drying chamber. In some embodiments, the droplets are sprayed into the chamber or centrifuged from a rotating disk. The microspheres are then dried in the heated chamber and fall to the bottom of the spray-drying chamber where they are collected. In some embodiments of the present invention, the micro spheres have triangular geometries, in other modalities, the micro spheres are aggregates of more sticky particles. In various modalities, the proton pump inhibitor and / or non-steroidal anti-inflammatory agents are present in the micro spheres in an amount greater than 1%, greater than 2.5%, greater than 5%, greater than 10%, greater to 15%, greater than 20%, greater than 25%, greater than 30%, greater than 35%, greater than 40%, greater than 45%, greater than 50%, greater than 55%, greater than 60%, greater at 65%, greater than 70%, greater than 75%, greater than 80%, greater than 85%, greater than 90%, greater than 95% or greater than 98% by weight of the proton pump inhibitor to the microencapsulation material used to improve the stability of the pharmaceutical composition or the material that masks the taste. COATINGS In accordance with another aspect of the present invention, all or part of the non-steroidal anti-inflammatory drug can be coated. In various embodiments contemplated by the present invention, the non-steroidal anti-inflammatory drug is coated, for example, with a gastric resistant coating such as enteric coating, controlled release coating, an enzyme control coating, a film coating, a sustained release coating. , an immediate release coating, a delayed release coating or a moisture barrier coating. See, for example, Remington's Pharmaceutical Sciences, 20th Edition (2000). According to another aspect of the invention, the non-steroidal anti-inflammatory agent is enteric coated. Suitable enteric coating materials include but are not limited to polymerized gelatin, shellac, methacrylic acid copolymer type C NF, cellulose butyrate, phthalate, cellulose hydrogen phthalate, cellulose propionate phthalate, polyvinyl acetate phthalate (PVAP), cellulose acetate phthalate (CAP) , cellulose acetate trimellitate (CAT), hydroxypropyl methylcellulose phthalate, hydroxypropyl methylcellulose acetate, dioxypropyl methylcellulose succinate, carboxymethyl ethylcellulose (CMEC), hydroxypropyl methylcellulose succinate and polymers and copolymers of acrylic acid, such as those formed from methyl acrylate, ethyl acrylate, methyl methacrylate and / or ethyl methacrylate with copolymers of esters of acrylic and methacrylic acid (for example Eudragit NE, Eudragit RL, Eudragit RS). In accordance with one aspect of the present invention, all or part of the proton pump inhibitor can be coated. In various embodiments contemplated by the present invention, the proton pump inhibitor is coated, for example, with a gastric resistant coating such as an enteric coating, controlled release coating, an enzyme control coating, a film coating, a release coating sustained, an immediate release coating, a delayed release coating or a moisture barrier coating. See, for example, Remington's Pharmaceutical Sciences, 20a. Edition (2000). According to another aspect of the invention, either the proton pump inhibitory agent or the non-steroidal anti-inflammatory agent is coated. In other aspects of the invention, some or all of the proton pump inhibitor and some or all of the non-steroidal anti-inflammatory agent are coated. According to another aspect of the invention, the dosage form (such as a tablet, coated tablet or capsule) is coated to aid swallowing. The proton pump inhibiting agent can be coated with the same material that is used to coat the non-steroidal anti-inflammatory agent or a different material. Additionally, the coating used to coat the entire dosage form (such as a film coating) may be the same as or different from the coating used to coat the proton pump inhibitory agent and / or the non-steroidal anti-inflammatory agent. Aguí pharmaceutical compositions are provided which have profiles of absorption of multiple sites of the non-steroidal anti-inflammatory drug. In accordance with one aspect of the invention, some of the non-steroidal anti-inflammatory drug is formulated for immediate release and some of the non-steroidal anti-inflammatory drug is formulated for delayed release. According to one aspect of the invention, the delayed release coating is an enteric coating. Pharmaceutical compositions which have absorption profiles of multiple sites of the proton pump inhibitor, agui are provided. According to one aspect of the invention, some of the proton pump inhibitor is formulated for immediate release and some of the portion of the proton pump inhibitor is formulated for delayed release. According to one aspect of the invention, the delayed release coating is an enteric coating. DOSAGE The pharmaceutical compositions of the present invention comprising a proton pump inhibitor and a non-steroidal anti-inflammatory agent are administered and dosed according to good medical practice, taking into account the clinical condition of the individual patient, the site and method of administration, the administration program and other factors known to those who practice medicine. In human therapy, it is important to provide a dosage form that delivers the required therapeutic amount of each therapeutic agent in vivo, and makes the therapeutic agent bioavailable in a rapid form. Proton Pump Inhibitory Agents The proton pump inhibitory agent is administered and dosed in accordance with good medical practice, taking into account the clinical condition of the individual patient, the site and method of administration, the administration schedule and other known factors by those who practice medicine. In human therapy, it is important to provide a dosage form that delivers the required therapeutic amount of each therapeutic agent in vivo and render the therapeutic agent bioavailable in a rapid manner. In addition to the dosage forms described here, the dosage forms described by Phillips et al. in the patents of the U.S.A. Nos. 6,489,346, 6,780,882 and 6,645,988 are incorporated herein by reference. The percent of intact drug that is absorbed into the bloodstream is not strictly critical, since not always as a therapeutically effective agent, for example an effective amount for gastrointestinal disorder of a proton pump inhibitory agent, is absorbed after administration of the pharmaceutical composition to a subject. Effective amounts for gastrointestinal disorder in tablets can be found in US Pat. number 5,622,719. It is understood that the amount of the proton pump inhibitory agent and / or buffering agent that is administered to a subject depends on a number of factors, for example sex, general health, diet and / or body weight of the subject. Illustratively, administration of a substituted bicyclic aryl imidazole to a minor or small animal such as a dog, a relatively low amount of the proton pump inhibitor, for example about 1 mg to about 30 mg, will often provide in blood serum consistent with therapeutic effectiveness. When the subject is a human adult or a larger animal, such as a horse, achievement of a therapeutically effective blood serum concentration will require two units of larger doses, for example about 10 mg, about 15 mg, about 20 mg , about 30 mg, about 40 mg, about 80 mg, or about 120 mg of dose for a human adult, or about 150 mg, or about 200 mg, or about 400 mg, or about 800 mg, or about 1000 mg of dose , or approximately 1500 mg of dose, or approximately 2000 mg of dose, or approximately 2500 mg of dose, or approximately 3000 mg of dose or approximately 3200 mg of dose or approximately 3500 mg of dose for an adult horse. In various other embodiments of the present invention, the amount of the proton pump inhibitor administered to a subject for example is about 0.5-2 mg / kg of body weight, or about 0.5 mg / kg of body weight, or about 1 mg / kg. Kg of body weight, or approximately 1.5 mg / Kg of body weight, or approximately 2 mg / Kg of body weight. Treatment doses in general can be titrated to optimize safety and efficacy.

Typically, effective dose ratios of in vitro and / or in vivo tests initially can provide useful guidance at doses suitable for administration to the subject. Studies in animal models in general can be employed for guidance regarding effective doses for treatment of gastrointestinal disorders or diseases according to the present invention. In terms of treatment protocol, it will be appreciated that the doses to be administered will depend on several factors, including the particular agent to be administered, the selected route for administration, the condition of the particular subject. In various embodiments, unit dosage forms for humans contain about 1 mg to about 120 mg, or about 1 mg, or about 5 mg, or about 10 mg, or about 15 mg, or about 20 mg, or about 30 mg, or about 40 mg, or about 50 mg, or about 60 mg, or about 70 mg, or about 80 mg, or about 90 mg, or about 100 mg, or about 110 mg, or about 120 mg of a pump inhibitor. protons In a further embodiment of the present invention, the pharmaceutical composition is administered in an amount to achieve a measurable serum concentration of a proton pump inhibitory agent not degraded by acid greater than about 0.1 g / ml within about 30 minutes after administration of the pharmaceutical composition. In another embodiment of the present invention, the pharmaceutical composition is administered to the subject in an amount to achieve a measurable serum concentration of a proton pump inhibitory agent not acidic or unreacted with acid greater than about 0.1 g / ml within about 15 minutes after administration of the pharmaceutical composition. In yet another embodiment, the pharmaceutical composition is administered to the subject in an amount to achieve a measurable concentration in serum of a proton pump inhibitory agent not degraded by acid or unreacted with acid, greater than about 0.1 g / ml within about 10 minutes after administration of the pharmaceutical composition. In yet another embodiment of the present invention, the composition is administered to the subject in an amount to achieve a measurable serum concentration of the proton pump inhibitory agent greater than about 0.15 g / ml within about 15 minutes and to maintain a concentration in proton pump inhibitory agent serum greater than about 0.15 g / ml from about 15 minutes to about one hour after administration of the composition. In still another embodiment of the present invention, the composition is administered to the subject in an amount to achieve a measurable serum concentration of the proton pump inhibitory agent greater than about 0.25 g / ml within about 15 minutes and maintain a serum concentration. of the proton pump inhibitory agent greater than about 0.25 g / ml from about 15 minutes to about one hour after administration of the composition. In another embodiment of the present invention, the composition is administered to the subject in an amount to achieve a measurable serum concentration of the proton pump inhibitory agent greater than about 0.35 g / ml within about 15 minutes and maintain a serum concentration of the proton pump inhibitory agent, greater than about 0.35 g / ml from about 15 minutes to about one hour after administration of the composition. In another embodiment of the present invention, the composition is administered to the subject in an amount to achieve a measurable serum concentration of the proton pump inhibitory agent greater than about 0.45 g / ml within about 15 minutes and to maintain a serum concentration. of the proton pump inhibitory agent greater than about 0.45 g / ml from about 15 minutes to about one hour, after administration of the composition. In another embodiment of the present invention, the composition is administered to the subject in an amount to achieve a measurable serum concentration of the proton pump inhibitory agent greater than about 0.15 g / ml within about 30 minutes and maintain a serum concentration of the proton pump inhibitory agent greater than about 0.15 g / ml from about 30 minutes to about one hour after administration of the composition. In yet another embodiment of the present invention, the composition is administered to the subject in an amount to achieve a measurable serum concentration of the proton pump inhibitory agent greater than about 0.25 g / ml within about 30 minutes and maintain a serum concentration. of the proton pump inhibitory agent greater than about 0.25 g / ml from about 30 minutes to about one hour after administration of the composition. In another embodiment of the present invention, the composition is administered to the subject in an amount to achieve a measurable serum concentration of the proton pump inhibitory agent greater than about 0.35 g / ml within about 30 minutes and maintain a serum concentration of the proton pump inhibitory agent greater than about 0.35 g / ml from about 30 minutes to about one hour after administration of the composition. In another embodiment of the present invention, the composition is administered to the subject in an amount to achieve a measurable serum concentration of the proton pump inhibitory agent greater than about 0.45 g / ml within about 30 minutes and to maintain a serum concentration. of the proton pump inhibitory agent greater than about 0.45 g / ml from about 30 minutes to about one hour after administration of the composition. In still another embodiment of the present invention, the composition is administered to the subject in an amount to achieve a measurable serum concentration of the proton pump inhibitory agent not degraded with acid or unreacted with acid, greater than about 0.5 g / ml within about one hour after administration of the composition. In still another embodiment of the present invention, the composition is administered to the subject in an amount to achieve a measurable serum concentration of the proton pump inhibitory agent not degraded with acid or unreacted with acid greater than about 0.3 g / ml within about 45 minutes after administration of the composition. Contemplated compositions of the present invention provide a therapeutic effect as proton pump inhibitory agent medicaments in a range of from about 5 minutes to about 24 hours after administration, allowing for example, if desired, a once-a-day administration, twice a day, three times a day, etc. Generally speaking, it will be desired to administer a quantity of compound which is effective to achieve a serum level proportional to the concentrations which are effective in vivo for a period of time effective to produce a therapeutic effect. Determination of these parameters is well within the skill in the specialty. These considerations are well known in the art and are described in standard textbooks. In one embodiment of the present invention, the composition is administered to a subject in an amount effective for gastrointestinal disorder, that is, the composition is administered in an amount that achieves a therapeutically effective dose of a proton pump inhibitory agent in the serum. of a subject's blood, for a period of time, to produce a desired therapeutic effect. Illustratively, a fasted human adult (who fasts in general at least 10 hours), the composition is administered to achieve a therapeutically effective dose of a proton pump inhibitory agent in the blood serum of a subject within about 45 minutes after administration of the composition. In another embodiment of the present invention, a therapeutically effective dose of the proton pump inhibitory agent is achieved in the subject's blood serum within approximately 30 minutes from the time of administration of the composition to the subject. In yet another embodiment, a therapeutically effective dose of the proton pump inhibitory agent is achieved in the blood serum of a subject within approximately 20 minutes from the time of administration to the subject. In yet another embodiment of the present invention, a therapeutically effective dose of the proton pump inhibitory agent is achieved in the blood serum of a subject at about 15 minutes from the time of administration of the composition to the subject. In additional modalities, more than about 98%; or more than about 95%; or more than about 90%; or more than about 75%; or more than about 50% of the drug absorbed in the bloodstream, is a form not degraded with acid or not reacted with acid. In other embodiments, the pharmaceutical compositions provide a release profile of the proton pump inhibitor using USP dissolution methods, wherein more than about 50% of the proton pump inhibitor is released from the composition within about two hours; or more than 50% of the proton pump inhibitor is released from the composition within about 1.5 hours; or more than 50% of the proton pump inhibitor is released from the composition within about 1 hour after exposure to gastrointestinal fluid. In another embodiment, more than about 60% of the proton pump inhibitor is released from the composition within about 2 hours; or more than 60% of the proton pump inhibitor is released from the composition within about 1.5 hours; or more than 60% of the proton pump inhibitor is released from the composition within about 1 hour after exposure to gastrointestinal fluid. In yet another embodiment, more than about 70% of the proton pump inhibitor is released from the composition within about 2 hours; or more than 70% of the proton pump inhibitor is released from the composition within about 1.5 hours; or more than 70% of the proton pump inhibitor is released from the composition within about 1 hour after exposure to gastrointestinal fluid. Non-Steroidal Anti-Inflammatory Agents The nonsteroidal anti-inflammatory agent is administered and dosed according to good medical practice, taking into account the clinical condition of the individual patient, the site and method of administration, administration schedule and other known factors for who practice medicine. According to one aspect of the invention, the pharmaceutical composition comprises two different non-steroidal anti-inflammatory drugs. According to another aspect of the invention, the pharmaceutical composition comprises two different non-steroidal anti-inflammatory drugs, wherein at least one of the non-steroidal anti-inflammatory drugs is a COX-II inhibitor. In therapy for humans, it is important to provide a dosage form that will supply the required therapeutic amount of the drug in vivo, and make the drug bio-available at the appropriate time. According to one aspect of the invention, part of the non-steroidal anti-inflammatory drug is in an immediate release form and part of the non-steroidal anti-inflammatory drug is in a deliberate delayed form. According to another aspect of the invention, two therapeutically effective doses are present in the pharmaceutical composition, one in an immediate release form and the other in a delayed release form. The dosage of non-steroidal anti-inflammatory agents will vary but can be easily determined by a person skilled in the art. DOSAGE FORM The pharmaceutical compositions of the present invention contain desired amounts of proton pump inhibitor, a buffering agent and a non-steroidal anti-inflammatory drug and may be in the form of: a tablet, (including a suspension tablet, a chewable tablet, a fast-melting tablet, a bite-disintegrating tablet, a fast-disintegrating tablet, an effervescent tablet, or a coated tablet), a pill, a powder (including a sterile packing powder, a powder to supply, or an effervescent powder), a capsule (including soft or hard capsules, for example capsules made from animal derived gelatin or HPMC derived from plants), a pill, a sachet, a troche, granules, pellets, or an aerosol. These pharmaceutical compositions of the present invention can be manufactured by conventional pharmacological techniques. Conventional pharmacological techniques include, for example, one or a combination of methods: (1) dry mixing, (2) direct compression, (3) grinding, (4) dry or non-aqueous granulation, (5) wet granulation or (6) melting. See for example Lachman et al. , The Theory and Practice of Industrial Pharmacy (1986). Other methods include, for example, granulation, spray drying, tray coating, melt granulation, granulation, wurster coating, tangential coating, top coating, tabletting, extrusion, coacervation and the like. In one embodiment, the proton pump inhibitor and the non-steroidal anti-inflammatory drug are microencapsulated before being formulated into one of the higher forms. In another embodiment, all or some of the proton pump inhibitor is microencapsulated before being formulated in one of the above forms. In another embodiment, some or all of the buffering agent is micro-encapsulated before being formulated in one of the foregoing forms. In other embodiments, all or some of the non-steroidal anti-inflammatory drug is microencapsulated before being further formulated in one of the above forms. In yet another embodiment, some or all of the non-steroidal anti-inflammatory drug is coated before being further formulated in one of the foregoing ways by using standard coating methods, such as those described in Remington's Pharmaceutical Sciences, 20a. Edition (2000). Still in other embodiments contemplated by the present invention, film coating is provided around the pharmaceutical composition. In other embodiments, the pharmaceutical compositions further comprise one or more additional materials such as a pharmaceutically compatible carrier, binder, filler, suspending agent, flavoring agent, sweetening agent, disintegrating agent, surfactant, preservative, lubricant, dye, diluent, solubilizer, wetting agent, stabilizer, wetting agent, anti-adherent, parietal cell activator, antifoaming agent, antioxidant, chelating agent, antifungal agent, antibacterial agent or one or more of its combinations. Parietal cell activators are administered in an amount sufficient to produce the desired stimulatory effect, without causing undesirable side effects to patients. In one embodiment, the parietal cell activator is administered in an amount of about 5 mg to about 2.5 g per 20 mg dose of the proton pump inhibitor. In other embodiments, one or more layers of the pharmaceutical formulation are plasticized. Illustratively, a plasticizer in general is a solid or liquid of high boiling point. Suitable plasticizers can be added from about 0.01% to about 50% by weight (w / w) of the coating composition. Plasticizers include, for example diethyl phthalate, citrate esters, polyethylene glycol, glycerol, acetylated glycerides, triacetin, polypropylene glycol, polyethylene glycol, triethyl citrate, dibutyl sebacate, stearic acid, stearol, stearate and castor oil. EXAMPLE SOLID ORAL DOSAGE COMPOSITIONS Solid oral dose compositions, for example tablets, chewable tablets, effervescent tablets, coated tablets and capsules, are prepared by mixing the proton pump inhibitor, one or more buffering agents, at least one anti-cancer drug. -non-steroidal inflammation, and pharmaceutical excipients, to form a mixture composition in volume. When referring to these compositions of bulk mixtures as homogeneous, it is implied that the proton pump inhibitor, buffering agent and nonsteroidal anti-inflammatory drug are dispersed uniformly throughout the composition such that the composition can easily subdivided into equally effective unit dose forms, such as tablets, pills and capsules. Individual unit doses may also comprise film coatings, which disintegrate before oral ingestion or before contact with diluent. Compressed tablets are solid dosage forms prepared by compacting the volume mixing compositions described above. In various embodiments, compressed tablets of the present invention will comprise one or more functional excipients such as binding and / or disintegrating agents. In other embodiments, the compressed tablets will comprise the film that surrounds the final compressed tablet. In other embodiments, the compressed tablets comprise one or more excipients and / or flavoring agents. A chewable tablet can be prepared by compacting bulk mixing compositions, described above. In one embodiment, the chewable tablet comprises a material useful for improving the shelf life of the pharmaceutical composition. In another embodiment, micro encapsulated material has properties that mask taste. In various other embodiments, the chewable tablet comprises one or more flavoring agents and one or more materials that store the taste. In still other embodiments, the chewable tablet comprises both a material useful for improving the shelf life of the pharmaceutical formulation and one or more flavoring agents. In various embodiments, the encapsulated micro-proton pump inhibitor, buffering agent, non-steroidal anti-inflammatory drug, and optionally one or more excipients are dry mixed and compressed into a mass, such as a tablet having a sufficient hardness to provide a pharmaceutical composition which substantially disintegrates in less than about 30 minutes, less than about 35 minutes, less than about 40 minutes, less than about 45 minutes, less than about 50 minutes, less than about 55 minutes or less than about 60 minutes , after oral administration, thereby releasing the buffering agent and the proton pump inhibitor in the gastrointestinal fluid. When at least 50% of the pharmaceutical composition has disintegrated, the compressed mass has substantially disintegrated. A capsule can be prepared by placing the bulk composition composition, described above within a capsule. EXEMPLARY DUST COMPOSITIONS A powder for suspension can be prepared the proton pump inhibitor, one or more buffering agents and one or more non-steroidal anti-inflammatory drugs. In various embodiments, the powder may comprise one or more pharmaceutical excipients and flavors. The powder for suspension is prepared by mixing the proton pump inhibitor, one or more buffering agents, one or more non-steroidal anti-inflammatory drugs and optional pharmaceutical excipients to form a bulk mixing composition. This volume mixture is uniformly subdivided into unit dose packaging or multiple dose packet units. The term "uniform" means the homogeneity of the mixture in volume is maintained substantially during the packaging process. In some embodiments, some or all of the proton pump inhibitor is micronized. In other modalities, some or all of the non-steroidal anti-inflammatory drug is micronized. Additional embodiments of the present invention also comprise a suspending agent and / or a wetting agent. Effervescent powders are also prepared according to the present invention. Effervescent salts have been used to supply medicines in water for oral administration. Effervescent salts are coarse granules or powders which contain a medicinal agent and a dry mixture, usually composed of sodium bicarbonate, citric acid and / or tartaric acid. When the salts of the present invention are added to the water, the acids and the base react to liberate carbon dioxide gas, thereby causing "effervescence". Examples of effervescent salts include the following ingredients: sodium bicarbonate or a mixture of sodium bicarbonate and sodium carbonate, citric acid and / or tartaric acid. Any acid-base combination that results in the release of carbon dioxide, the combination of sodium bicarbonate and citric and tartaric acids can be used instead, provided the ingredients are suitable for pharmaceutical use and will result in a pH of approximately 6.0 or higher . The method of preparing the effervescent granules of the present invention employs three basic processes: wet granulation, dry granulation and melting. The melting method is used for the preparation of most commercial effervescent powders. It will be noted that, although these methods are intended for the preparation of granules, the effervescent salt formulation of the present invention can also be prepared as tablets according to the known technology for tablet preparation. Wet granulation is one of the oldest methods of granule preparation. The individual steps in the wet granulation process of tablet preparation include grinding and sieving the ingredients, mixing dry powder, wet kneading, granulation and final grinding. In various embodiments, the micro encapsulated PPI is added to the other excipients of the pharmaceutical composition after they have been wet granulated. Dry granulation involves compressing a powder mix into a raw finishing tablet or "posta" on the heavy-duty rotary tablet press. The posts are then broken into granular particles by a grinding operation, usually by passage through an oscillating granulator. The individual stages include powder mixing, compression (post extrusion) and grinding (post reduction or granulation). No wet binder or moisture is involved in any of the stages. In some embodiments, the micro encapsulated PPI is dry granulated with other excipients in the pharmaceutical composition. In other embodiments, the micro encapsulated omeprazole is added to the other excipients of the pharmaceutical composition after they have been dry granulated. SUSPENSION POWDER Compositions are provided comprising a pharmaceutical composition comprising at least one proton pump inhibitor, at least one buffering agent and at least one non-steroidal anti-inflammatory agent, and at least one suspending agent for oral administration to a subject. The composition can be a powder for suspension and when mixed with water, a substantially uniform suspension is obtained. A suspension is "substantially uniform" when it is primarily homogeneous, that is, when the suspension is composed of approximately the same concentration of proton pump inhibitor at any point throughout the suspension. A suspension is determined to be composed of approximately the same concentration of proton pump inhibitor through the suspension, when there is less than about 20%, less than about 15%, less than about 13%, less than about 11%, less than about 10%, less than about 8%, less than about 5%, or less than about 3% variation in concentration between samples taken from various points in the suspension. The concentration at various points throughout the suspension can be determined by any convenient means known in the art. For example, a convenient method to determine concentration at various points involves dividing the suspension into three substantially equal sections: upper, middle and lower. The layers are split starting at the top of the suspension and ending at the bottom of the suspension. Any number of suitable sections can be used to determine the best uniformity of the suspension, such as for example two sections, three sections, four sections, five sections or six or more sections. Sections can be named in any appropriate way, such as in relation to their location (eg, upper, middle, lower), numbered (eg, one, two, three, four, five, six, etc.), or with letters (eg, A, B , C, D, E, F, G, etc.). The sections can be divided into any convenient configuration. In one embodiment, the sections are divided from the top to the bottom, which allows a comparison of sections of the upper part and sections from the bottom, in order to determine if and at what speed the proton pump inhibitor is sedimenting in the Background sections. Any number of appropriate sections assigned to determine uniformity of the suspension can be evaluated, such as for example all sections, 90% of sections, 75% of sections, 50% of sections, or any other number of convenient sections . The concentration is easily determined by methods known in the art, such as, for example, the methods described herein. In one embodiment, the concentration is determined using percent of declared quantity. "Percent declared amount" (% declared amount) is calculated using the current amount of proton pump inhibitor or non-steroidal anti-inflammatory drug per sample compared to the intended amount of proton pump inhibitor or nonsteroidal anti-inflammatory drug per sample. The intended amount of proton pump inhibitor or non-steroidal anti-inflammatory drug per sample can be determined based on the formulation protocol or from any other convenient method, such as for example by reference to the "declared amount", ie , the intended quantity of the proton pump inhibitor or non-steroidal anti-inflammatory drug illustrated on the label or packaging, in compliance with the regulations promulgated by the US Food and Drug Administration (United States Food and Drug Administration). In one aspect of the present invention, the suspension is divided into sections and the percent declared quantity is determined for each section. The suspension is determined to be substantially uniform if it comprises at least one of a) at least about one percent of declared amount threshold established through the evaluation sections or b) has less than one percent variation established in percent of quantity declared through the evaluation sections. The suspension may comprise any of a) or b) or may comprise both a) and b). The evaluated sections of the suspension may have any percent declared quantity threshold adequate to determine that the suspension is substantially uniform. For example, the sections may comprise, for example at least about 70, at least about 75, at least about 80, at least about 85, at least about 87, at least about 88, at least about 89, at least about 90, at least about 93, at least about 95, at least about 98, at least about 100, at least about 105, at least about 110, at least about 115 percent declared amount of the proton pump inhibitor or any interval that falls there, such as for example from about 80 to about 115, from about 85 to about 110, from about 87 to about 108, from about 89 to about 106, from about 90 to about 105, and so forth, percent of declared amount of proton pump inhibitor. The sections of the evaluated suspension may have less than any percent of evaluation established in percent of declared amount, adequate to determine that the suspension is substantially uniform such as for example about 25%, about 20%, about 17%, about 15%. %, approximately 13%, approximately 11%, approximately 10%, approximately 7%, approximately 5%, approximately 3% or approximately 0% variation. In another aspect of the present invention, the suspension is substantially uniform if it comprises at least one of a) at least about 87% of declared amount of proton pump inhibitor in the upper, middle and lower sections, determined by separating the suspension in three substantially equal sections of the upper part to the bottom for at least about 5 minutes and after mixing with water, or b) less than about 11% variation in percent of declared amount between each of the upper, middle and bottom sections , for at least about 5 minutes after mixing with water. In an alternate aspect of the present invention, the suspension is substantially uniform, if it comprises at least one of a) at least about 80% of the declared amount of the proton pump inhibitor in the upper, middle and lower sections, determined by separating the suspension is three substantially equal sections from the top to the bottom for at least about 60 minutes after mixing with water or b) less than about 15% variation in percent of declared amount between each of the upper sections, medium and bottom or bottom, for at least about 60 minutes after mixing with water. In some embodiments, the composition will remain substantially uniform for a convenient amount of time corresponding to the intended use of the composition, such as for example for at least about 5 minutes, about 10 minutes, about 15 minutes, about 20 minutes, about 30 minutes about 45 minutes, about 60 minutes (1 hour), about 75 minutes, about 90 minutes, about 105 minutes, about 120 minutes (2 hours), about 150 minutes, about 180 minutes (3 hours), about 210 minutes, about 4 hours, approximately 5 hours or more after mixing with water. In one embodiment, the suspension remains substantially uniform from about 5 minutes to about 4 hours after mixing with water. In another embodiment, the suspension remains substantially uniform from about 15 minutes to about 3 hours after mixing with water. In yet another embodiment, the suspension remains substantially uniform from at least about 1 hour to at least about 3 hours after mixing with water. In one embodiment of the present invention, the composition will remain substantially uniform at least until the suspension is prepared for administration to the patient. The suspension can be prepared for administration to the patient at any time after mixing as long as the suspension remains substantially uniform. In another embodiment, the suspension is prepared for administration to the patient from any time after mixing until the suspension is no more uniform. For example, the suspension can be prepared for administration to the patient of about 5 minutes, about 10 minutes, about 15 minutes, about 20 minutes, about 30 minutes, about 45 minutes, about 60 minutes (1 hour), about 75 minutes, about 90 minutes, approximately 105 minutes, approximately 120 minutes (2 hours), approximately 150 minutes, approximately 180 minutes (3 hours), approximately 210 minutes, approximately 4 hours, approximately 5 hours or more after mixing with water. In one embodiment, the suspension is prepared for administration to the patient from about 5 minutes to about 4 hours after mixing. In another embodiment, the suspension is prepared for administration to the patient from about 15 minutes to about 3 hours after mixing. In yet another embodiment, the suspension is prepared for administration to the patient of at least about 1 hour to at least about 3 hours after mixing. In an alternate embodiment, the composition remains substantially uniform until the composition is currently administered to the patient. The suspension can be administered to the patient at any time after mixing, as long as the suspension remains substantially uniform. In one embodiment, the suspension is prepared for administration to the patient from any time after mixing until the suspension is no longer uniform. For example, the suspension can be administered to the patient of about 5 minutes, about 10 minutes, about 15 minutes, about 20 minutes, about 30 minutes, about 45 minutes, about 60 minutes (1 hour), about 75 minutes, about 90 minutes, about 105 minutes, about 120 minutes (2 hours), about 150 minutes, about 180 minutes (3 hours), about 210 minutes, about 4 hours, about 5 hours or more after mixing with water. In one embodiment, the suspension is administered to the patient from about 5 minutes to about 4 hours after mixing. In another modality, the suspension is administered to the patient from about 15 minutes to about 3 hours after mixing. In yet another embodiment, the suspension is administered to the patient from at least about 1 hour to at least about 3 hours after mixing. In one embodiment, the composition comprises at least one proton pump inhibitor, at least one buffering agent, at least one non-steroidal anti-inflammatory agent, and xanthan gum. The composition is a powder for suspension, and upon mixing with water, a first suspension is obtained which is substantially more uniform when compared to a second suspension comprising the proton pump inhibitor, the buffering agent, the non-steroidal anti-inflammatory agent and suspension agent, where the suspending agent is not xanthan gum. In one embodiment, the first suspension comprises at least one of a) at least about 87% of declared amount of proton pump inhibitor in the upper, middle and lower section, determined by separating the suspension into three substantially equal sections of the part above the bottom by at least about 5 minutes after mixing with water, or b) less than about 11% variation in percent declared amount between each of the upper, middle and lower sections by at least about 5 minutes after mixing with water. In another embodiment, the first suspension comprises at least one of a) at least about 80% of the declared amount of proton pump inhibitor in the upper, middle and lower sections determined by separating the suspension into three substantially equal sections of the upper part. at the bottom, for at least about sixty minutes after mixing with water, or b) less than about 15% variation in percent declared amount between each of the upper, middle and lower sections for at least about sixty minutes after mixing with water. In one embodiment, the composition comprises omeprazole, sodium bicarbonate and xanthan gum. The composition is a powder for suspension and before mixing with water, a substantially uniform suspension is obtained. In one embodiment, the suspension comprises at least one of a) at least about 87% of declared amount of proton pump inhibitor in the upper, middle and lower section, determined by separating the suspension into three substantially equal sections of the upper part. at the bottom for at least about 5 minutes after mixing with water, or b) less than about 11% variation in percent declared amount between each of the upper, middle and lower sections by at least about 5 minutes after mixing with Water. In another embodiment, the suspension comprises at least one of a) at least about 80% of the declared amount of proton pump inhibitor in the upper, middle and lower sections determined by separating the suspension into three substantially equal sections of the upper part of the suspension. bottom for at least about sixty minutes after mixing with water, or b) less than about 15% variation in percent declared amount between each of the upper, middle and lower sections for at least about sixty minutes after mixing with water . In yet another embodiment, the composition comprises omeprazole, sodium bicarbonate, at least one non-steroidal anti-inflammatory agent, xanthan gum and at least one sweetening or flavoring agent. The composition is a powder for suspension. Upon mixing with water, a substantially uniform suspension is obtained. In one embodiment, the suspension comprises at least one of a) at least about 87% of declared amount of proton pump inhibitor in the upper, middle and lower section, determined by separating the suspension into three substantially equal sections of the upper part. at the bottom for at least about 5 minutes after mixing with water, or b) less than about 11% variation in percent declared amount between each of the upper, middle and lower sections by at least about 5 minutes after mixing with water. In another embodiment, the suspension comprises at least one of a) at least about 80% of the declared amount of proton pump inhibitor in the upper, middle and lower sections determined by separating the suspension into three substantially equal sections of the upper part of the suspension. bottom for at least about sixty minutes after mixing with water, or b) less than about 15% variation in percent declared amount between each of the upper, middle and lower sections for at least about sixty minutes after mixing with water . Other Exemplary Compositions Pharmaceutical compositions suitable for buccal or sublingual administration, include solid dosage forms or intra-oral batches, for example pellets. Other types of release delivery systems are available and known to those skilled in the art. Examples of these delivery systems include but are not limited to: polymer-based systems, such as polylactic acid, polyglycolic acid, polyanhydrides and polycaprolactone; non-polymer based systems which are lipids, including sterols such as cholesterol, cholesterol esters and neutral fatty or fatty acids, such as mono-, di- and triglycerides; hydrogen evolution systems (hydrogel); silastic systems; peptide-based systems; wax coatings; compressed tablets using conventional binders and excipients, partially fused implants and the like. See, for example, Liberman et al. , Pharmaceutical Dosage Forms, 2 Ed., Vol. 1, 209 (1990). For brevity, all patents and other references cited herein are incorporated by reference in their entirety. EXAMPLES The present invention is further illustrated by the following example, which will not be considered as limiting in any way. The experimental procedures for generating the data shown are discussed in more detail below. For all formulations herein, multiple doses may be formulated proportionally as is known in the art. The coatings, layers and encapsulations are applied in conventional ways using conventional equipment for these purposes. The invention has been described in an illustrative form and it will be understood that the terminology employed is intended in the nature of description rather than limitation. Example 1: Microencapsulation process with centrifugal disc The basic operation for the solvent-centrifugal disc process employed is as follows: an encapsulation solution is prepared by dissolving the encapsulation material in the appropriate solvent. The proton pump inhibitor (PPI = proton pump inhibitor) in combination with the buffering agent and non-steroidal anti-inflammatory agent, or proton pump inhibitor only if microencapsulation is intended, and then combined with a buffering agent and an anti-inflammatory agent. -non-steroidal inflammatory, disperses in the coating solution and feeds the center of the spinning disc. A thin film is produced across the surface of the disc and atomization occurs as the coating material leaves the periphery of the disc. The microspheres are formed by removing the solvent using hot air flow inside the atomization chamber and collecting as a free-flowing powder using a cyclone separator. Example 2: Microencapsulation process of spray drying A spray dryer consists of the same components as a spinning disk except that atomization is achieved through an air nozzle instead of a spin disk. Example 3: Powder Preparation for Oral Dosage Suspension. Powder for suspension (oral and liquid pharmaceutical composition) according to the present invention, is prepared by mixing PPI (40 mg of omeprazole in the form of microencapsulated omeprazole, omeprazole powder or omeprazole base) with at least one buffering agent and one agent Non-steroidal anti-inflammatory. In one embodiment, omeprazole or another proton pump inhibitor, which can be obtained from powder, capsules, tablets or from the solution for parenteral administration, is mixed with sodium bicarbonate (1680 mg), non-steroidal anti-inflammatory drug and sweeteners and flavors. Example 4: Microencapsulated Proton Pump Inhibitor The amount of microencapsulated omeprazole used in each batch of tablets varies based on the current loading of each set of microcapsules to achieve the theoretical dose of 40 mg. The omeprazole is microencapsulated in a manner similar to that described in Example 1 and Example 2. All the ingredients are mixed well to achieve a homogeneous mixture. Micro spheres of omeprazole were prepared using a high speed rotary tablet press (TBCB Pharmaceutical Equipment Group, Model ZPY15). Round, convex tablets with approximate diameters of 10 mm and an approximate average weight of 600 mg per tablet were prepared. Table 4. A.

Stability studies were performed on the microencapsulated omeprazole. The various tablets used in the stability studies were manufactured using the following materials: encapsulated omeprazole, sodium bicarbonate (1260 mg), calcium carbonate (790 mg), croscarmellose sodium (64 mg), Klucel (160 mg), Xylitab 100 (380 mg), microcrystalline cellulose (128 mg), sucralose (162 mg), mint durarimer (34 mg), peach durarimer (100 mg), masking powder (60 mg), FD & C Lacquer No. 40 Red (3 mg), and magnesium stearate (32 mg). An exemplary formulation employed to produce each of the tablets, as well as the mixing methods employed, are illustrated in Table 4. B. , following . Table 4 B.

Sample Method and Material of Solvent Temp Expenses micro weight of the input power encapsumaterial tion / lation (g / min) CC output) 53 Drying by Methocel 4.2 125/70 spray * Al5 LV PEG Water 3350 54 Drying by Methocel 4.0 125/70 spray Water Al5 LV BHT 55 Drying by Opadry YS- 4.2 126/60 spray Water 1-7003 PEG * Employs a concentric nozzle with an air opening of .139 cm (0.055 inch) and a fluid opening of .071 cm (0.028 inch). ** Uses a 7.62 cm (3 inch) stainless steel disc that rotates at approximately 4,500 rpm. Example 5j Stability of Omeprazole Microencapsulation The tablets used in the stability study were packed in 60 ml bottles of HDPE 33/400 with two 2-in-1 cans of 1-gram secant. The HDPE bottles were closed by hand pressing and sealed by induction using a 33/400 CRC SFGD 75M cap with a polypropylene liner. Samples were placed in controlled environmental chambers that were maintained at 25 + 2 ° C / 60 + 5% RH and 40 + 2 ° C / 75 + 5% RH. Microspheres that exhibited dissolution results with more than 80% omeprazole release after 2 hours were placed in stability. The microspheres were stored in open ampules at 25 ° C. All samples showed degradation after 4 weeks at elevated temperatures. The open ampoules stored at 25 ° C were analyzed after 6 to 8 hours for potency and for impurities using the Omeprazole EP method. The stability results are solved in Table 5.A. Table 5.A.

Load Material of Power Values Purity Microencapsulation OME 4- weeks (Loading of AUC * (Initial) Omeprazole) Methocel A15LV, PEG 2.2 2.3 (106% of 76.16 3350 (5%), BHT (0.1%) initial) @ 25 ° C and Baking soda Opadry YS-1-7003 PEG 20.5 22.6 (110% of the 100.0 3350 (5%) BHT (0.1%) initial) @ 25 ° C Kollicoat IR, PEG 26.2 23.8 (90.8% of 99.54 3350 (5%) &BHT initial) @ 25 ° C Eudragit RD 100, PEG 21.3 19.1 (89.5% of 98.88 3350 (5%) &initial BHT) @ 25 ° C (0.1%) Klucel (HPC), PEG 26.0 22.8 (87.8% of the 99.70 3350 (5%) & Initial BHT) @ 25 ° C (0.1%) Ethocel (50%) 25.8 21.9 (84.9% of the 98.22 Methocel E5 (50%) initial) © 25 ° C (99.3@T0) Klucel 22.2 20.7 (93. 2% of the initial 97.69) @ 25 ° C Kollicoat IR and 26.0 21.7 (83.6% of the 97.88 Initial sodium bicarbonate) @ 25 ° C * Purity AUC = Area under the Curve after 6 to 8 weeks at 25 ° C in open container.

Example 6: Capsule Formulations The following specific formulations are provided by way of reference only and are not intended to limit the scope of the invention. Each formulation contains therapeutically effective doses of PPI and non-steroidal anti-inflammatory, as well as enough buffering agent to prevent acid degradation and at least some of the PPI, by raising the pH of the gastric fluid. Amounts of buffer are expressed in weight as well as in molar equivalents (mEq). Amounts of non-steroidal anti-inflammatory agents are typically expressed in an amount per unit dose. The capsules are prepared by mixing the PPI and the steroidal anti-inflammatory agent with buffering agents, and mixing homogeneously with excipients, as shown in Tables 6.. to 6.H. next. The appropriate weight of the bulk composition is filled into a hard gelatin capsule (eg size 00) using an automatic encapsulator (H &K 1500 or MG2 G60). Table 6.A. Omeprazole capsule (20mg) -Ibuprofen (250mg) Table 6.B. Omeprazole capsules (40mg) -Meloxicam (15mg) Table 6.C. Lansoprazole capsules (15 mg) -Cetoprofen (75 mg) Table 6.D. Lansoprazole capsule (3Omg) -Piroxicam (20mg) Table 6.E. Omeprazole capsule (60 mg) -Rofecoxib (25 mgs) Table 6.F. Omeprazole capsule (60 mg) -Valdecoxib (20 mg) Table 6.G. Omeprazole capsule (10 mg) -Piroxicam (10 mg) Table 6.H. Omeprazole capsule (40 mg) - aspirin with enteric coating (100 mg) Example 7: Tablet Formulations The following specific formulations are provided by way of reference only and are not intended to limit the scope of the invention. Each formulation contains therapeutically effective doses of PPI and non-steroidal anti-inflammatory drug, as well as sufficient buffering agent to prevent acidic degradation of at least some PPI by raising the pH of the gastric fluid. Amounts of buffer are expressed in weight as well as in molar equivalents (mEg). Amounts of nonsteroidal anti-inflammatory drugs are typically expressed in an amount per unit dose. The tablets are prepared by mixing the PPI and the non-steroidal anti-inflammatory drug with buffering agents, and mixing homogeneously with excipients as illustrated in Tables 7.A. to 7.H. next. The appropriate weight of the volume mixing composition is compressed using 1.27 cm (1/2 inch) FFBE tools on a rotary press (Manesty Epxress) to achieve a hardness of 20-24 kPa. Table 7.A. Omeprazole tablet (20 mg) - Paracetamol (300 mg) Table 7.B. Omeprazole tablet (40 mg) - Aspirin (81 mg) Table 7.C. Lansoprazole tablet (15 mg) -Indometacin (75 mg) Table 7.D. Lansoprazole tablet (30 mg) -Celecoxib (100 mg) Table 7.E. Omeprazole Tablet (60mg) -Sulindac (200mg) Table 7.F. Omeprazole tablet (60 mg) -Naproxen (200 mg) Table 7.G. Omeprazole tablet (10 mg) -Ibuprofen (200 mg) PPI Buffering Agent NSAID Excipient mg of 13.7 mEq or 400 mg 200 mgs 20 mg of Ac-Di- omeprazole of Mg (OH) 3 3.0 mEq Ibupropene Sol 80 mg of microencapsulation or 250 mg of NaHC03 per Klucel 10 mg per tablet 16.7 m? Q or 650 mg tablet magnesium buffer stearate Table 7.H. Omeprazole tablet (40 mg) -Asprin (100 mg) E pp 8 Tablet Formulations Chewable The following specific formulations are provided by way of reference only and are not intended to limit the scope of the invention. Each formulation contains therapeutically effective doses of PPI and non-steroidal anti-inflammatory drug, as well as sufficient buffering agent to prevent acidic degradation of at least some of the PPI by raising the pH of the gastric fluid. Amounts of buffer are expressed in weight as well as in molar equivalents (mEg). Amounts of nonsteroidal anti-inflammatory drugs are typically expressed in an amount per unit dose. The tablets are prepared by mixing the PPI and the non-steroidal anti-inflammatory agent with buffering agents, and mixing homogeneously with excipients as illustrated in Tables 8.A to 8.H. next. The appropriate weight of the bulk or bulk mix composition is compressed using 5.5875 cm (5/8-inch) FFBE tools on a rotary press (Manesty Express) to achieve a hardness of 17-20 kPa. Table 8.A. Chewable Omeprazole Tablets (20 mg) -id Rofecoxib (25 mg) fifteen 0 Table 8.B. Chewable Omeprazole Tablets (40 mg) Diclofenac (100 mg) Table 8.C. Chewable Tablets of Lansoprazole (15mg) Ibuprofen (600mg) Table 8.D. Chewable Tablets of Lansoprazole (30 mg) Aspirin (800 mg) Table 8.E. Omeprazole Chewable Tablets (60mg) Oxaprozin (600mg) Table 8.F. Masticable Tablets Omeprazole (60 mg) Piroxicam (10 mg) Table 8.G. Omeprazole Chewable Tablets (10 mg) Ibuprofen (600 mg) Table 8.H. Omeprazole Chewable Tablets (40 mg) Asprin (100 mg) Example 9: Tablet Formulations Chewable Disintegration When Biting The following specific formulations are provided for reference only and are not intended to limit the scope of the invention. Each formulation contains therapeutically effective doses of PPI and non-steroidal anti-inflammatory drug as well as sufficient buffering agent to prevent acid degradation of at least some PPI by raising the pH of the gastric fluid. Amounts of buffer are expressed in weight as well as in molar equivalents (mEq). Amounts of nonsteroidal anti-inflammatory drug are typically expressed in an amount per unit dose. The tablets are prepared by mixing the PPI and the non-steroidal anti-inflammatory drug with buffering agents and mixing homogeneously with excipients as illustrated in Tables 9.A to 9.H. next. The appropriate weight of the volume mix composition is compressed using 5/8 inch FFBE tools on a rotary press (Manesty Express) to achieve a hardness of 8-12 kPa.

Table 9.A. Chewable tablets with disintegration when biting, of Omeprazole (20 mg) -Celecoxib (100 mg) Table 9.B. Chewable tablets with disintegration when biting Omeprazole (40 mg) -Diclofenac (100 mg) Table 9.C. Chewable tablets with disintegration when biting, Lansoprazole (15 mg) -Ibuprofen (600 mg) Table 9.D. Chewable tablets with disintegration when biting, of Lansoprazole (30 mg) -Aspirin (200 mg) Table 9.E. Chewable tablets with disintegration when biting Omeprazole (60 mg) -Cetoprofen (100 mg) PI Agent NSAID Excipient Amortiguador 60 mg of 15 mEq or 750 mg 100 mg of 60 mg of omeprazole of Mg (0H) 3 15 ketoprofen sucralose 60 mg microencapsulated mEq or 1260 mg per tablet of Ac-Di-Sol 60 per tablet of NaHC03 mg of starch 30 mEq or 210 mg pre-gelatinized buffer 30 mg of total Klucel 25 mg of cherry flavor 15 mg of magnesium stearate 3 mg of Red Lacquer to # 40 Table 9.F. Chewable tablets with disintegration when biting, of Omeprazole (60 mg) -Tenoxicam (20 mg) Table 9.G. Chewable tablets with disintegration when biting Omeprazole (lOmg) -Ibuprofen (500 mg) Table 9.H. Chewable tablets with disintegration when biting Omeprazole (40 mg) -Aspirin (100 mg) Example 10: Powder for Suspension Formulations The following specific formulations are provided for reference only and are not intended to limit the scope of the invention. Each formulation contains therapeutically effective doses of PPI and NSAIDs as well as sufficient buffering agent to prevent acidic degradation of at least some PPI by deriving the pH of gastric fluid. Table 10.A. Omeprazole (20 mg) -Ibuprofen (Continued) Table 10.B. Omeprazole (40 mg) - Indomethacin (Continued) Table 10.C. Omeprazole (60 mg) - Aspirin (Continuation) Example 11: Combination therapy for the treatment of GERD and / or ulcers including ulcers caused by NSAIDs and Inflammation / Pain For a combination treatment when a patient experiences both GERD and a disease state or inflammatory disorder, a formulation of the present invention is administered for relief of both gastric acid disorder and disease status or inflammatory disorder. The administration of a therapeutic amount of buffered PPI, without enteric coating, formulated for rapid absorption by supply to the stomach, in combination with a therapeutically effective amount of a non-steroidal anti-inflammatory drug, provides rapid relief of gastric acid pain and disease inflammatory The treatment may be provided by a chewable tablet, a suspension tablet, an effervescent tablet, a fast dissolving tablet or various liquid formulations and aqueous suspensions. Typical doses are as follows: 10-60 mg of PPI (omeprazole); 200-800 mgs of Ibuprofen; and 750-1500 mg of buffering agent. Effective amounts of other nonsteroidal anti-inflammatory agents are found in Table 1. To avoid a gastric acid disorder, a formulation of the present invention can be administered. The administration of a therapeutic amount of enteric coated buffer in PPI in combination with a therapeutically effective amount of a non-steroidal anti-inflammatory drug, prevents the non-steroidal anti-inflammatory drug from inducing a gastric acid-related disorder in the patient. The treatment is provided by an enteric coating capsule or tablet. Typical doses are as follows 20-40 mg of coated PPI, for example, omeprazole); a non-steroidal anti-inflammatory drug, for example, 200-800 mg Ibuprofen or 12-25 mg Rofecoxib; and 750 to 1500 mg of buffering agent. Effective amounts of other non-steroidal anti-inflammatory drugs are found in Table 1.

Modifications, eguivalents and variations of the present invention are possible in light of the above teachings, so that the invention can be incorporated in other forms without departing from the spirit or essential characteristic of the invention. The present embodiments will therefore be considered as illustrative and not restrictive, the scope of the invention is indicated by the appended claims rather than by the foregoing description. All the changes fall within the meaning and interval of claims of the claims, therefore they are intended to be covered therein.

Claims (52)

1. CLAIMS 1. A pharmaceutical composition, characterized by comprising: (a) a therapeutically effective amount of at least one labile acid proton pump inhibitor; (b) at least one buffering agent in an amount sufficient to increase the pH of gastric acid to a pH which prevents acidic degradation of at least some of the proton pump inhibitor in the gastric fluid; and (c) a therapeutically effective amount of at least one non-steroidal anti-inflammatory drug.
2. 2. The composition according to claim 1, characterized by an initial serum concentration of the proton pump inhibitor, is greater than about 0.1 / g / ml at any one time within about 30 minutes after administration of the composition.
3. 3. The composition according to claim 1, characterized in that the proton pump inhibitor is selected from the group consisting of omeprazole, hydroxymeprazole, esomeprazole, tenatoprazole, lansoprazole, pantoprazole, rabeprazole, dontoprazole, habeprazole, perprazole, ransoprazole, pariprazole, Leminoprazole; or a free base, free acid, salt, hydrate, amide ester, enantiomer, isomer, tautomer, polymorph or prodrug thereof.
4. 4. The composition according to claim 3, characterized in that the proton pump inhibitor is omeprazole or a free base, free acid, salt, hydrate, ester, amide, enantiomer, isomer, tautomer, polymorph or prodrug thereof.
5. The composition according to claim 1, characterized by comprising about 10 mg, 15 mg, 20 mg, 30 mg, 40 mg, or 80 mg of the proton pump inhibitor.
6. 6. The composition according to claim 1, characterized in that an initial serum concentration of the proton pump inhibitor is greater than about 0.5 g / ml at any time within about 1 hour after administration of the composition.
7. The composition according to claim 1, characterized in that the composition is administered in an amount to maintain a serum concentration of the proton pump inhibitor, greater than about 0.15 g / ml from about 15 minutes to about 1 hour after administration of the composition.
8. The composition according to claim 1, characterized in that upon oral administration to a subject, the composition provides a pharmacokinetic profile such that at least about 50% of the total area under the time curve versus serum concentration (AUC) for the Proton pump inhibitor occurs within approximately two hours after administration of a single dose of the composition to the subject.
9. The composition according to claim 1, characterized in that upon oral administration to the subject, the composition provides a pharmacokinetic profile such that the proton pump inhibitor reaches a maximum concentration in serum within about 1 hour after administration of a single dose of the composition.
10. The composition according to claim 1, characterized in that the proton pump inhibitor is microencapsulated with a material that improves the shelf life of the pharmaceutical composition.
11. The composition according to claim 10, characterized in that the material which improves the shelf life of the pharmaceutical composition is selected from the group consisting of: cellulose hydroxypropyl ethers, low substituted hydroxypropyl ethers, cellulose hydroxypropyl methyl ethers, polymers of ethylcellulose, ethylcelluloses and mixtures thereof, polyvinyl alcohol, hydroxyethylcelluloses, carboxymethylcelluloses, salts of carboxymethylcelluloses, copolymers of polyvinyl alcohol and polyethylene glycol, monoglycerides, triglycerides, polyethylene glycols, modified food starch, acrylic polymers, blends of acrylic polymers with cellulose ethers, cellulose acetate phthalate, sepifilms, cyclodextrins; and its mixtures.
12. The composition according to claim 1, characterized in that at least some of the non-steroidal anti-inflammatory drug is coated.
13. The composition according to claim 12, characterized in that the coating is chosen from a gastric resistance coating, a controlled release coating, an enzymatic control coating, a film coating, a sustained release coating, a coating of immediate release and a delayed release coating.
14. 14. The composition according to claim 1, characterized in that some of the proton pump inhibitor is coated.
15. 15. The composition according to claim 1, characterized in that the buffering agent is a salt of alkaline earth metal or a metal of group IA selected from a bicarbonate salt of a metal of Group IA, a carbonate salt of a metal of the Group. I.
16. 16. The composition according to claim 1, characterized in that the buffering agent is selected from the group consisting of: amino acid, an alkali metal salt of an amino acid, aluminum hydroxide, co-precipitated aluminum hydroxide / magnesium carbonate / calcium carbonate, aluminum magnesium hydroxide, co-precipitated aluminum hydroxide / magnesium hydroxide, co-precipitated aluminum hydroxide / sodium bicarbonate, aluminum glycinate, calcium acetate, calcium bicarbonate, calcium borate, carbonate calcium, calcium citrate, calcium gluconate, calcium glycerophosphate, calcium hydroxide, calcium lactate, calcium phthalate, calcium phosphate, calcium succinate, calcium tartrate, dibasic sodium phosphate, dipotassium hydrogen phosphate, phosphate dipotassium, disodium hydrogen phosphate, disodium succinate, dry aluminum hydroxide gel, L-arginine, magnesium acetate, magnesium aluminate, magnesium borate sio, magnesium bicarbonate, magnesium carbonate, magnesium citrate, magnesium gluconate, magnesium hydroxide, magnesium lactate, magnesium aluminate metasilicate, magnesium oxide, magnesium phthalate, magnesium phosphate, magnesium silicate, magnesium succinate , magnesium tartrate, potassium acetate, potassium carbonate, potassium bicarbonate, potassium borate, potassium citrate, potassium metaphosphate, potassium phthalate, potassium phosphate, potassium polyphosphate, potassium pyrophosphate, potassium succinate, tartrate of potassium, sodium acetate, sodium bicarbonate, sodium borate, sodium carbonate, sodium citrate, sodium gluconate, sodium hydrogen phosphate, sodium hydroxide, sodium lactate, sodium phthalate, sodium phosphate, polyphosphate sodium, sodium pyrophosphate, sodium sesquicarbonate, sodium succinate, sodium tartrate, sodium tripolyphosphate, synthetic hydrotalcite, tetrapotassium pyrophosphate, tetrasodium pyrophosphate, tripotassium phosphate, trisodium phosphate, trometamol and their mixtures.
17. 17. The composition according to claim 1, characterized in that the buffering agent is selected from sodium bicarbonate, sodium carbonate, magnesium carbonate, aluminum hydroxide, calcium carbonate, magnesium hydroxide, calcium oxide and mixtures thereof.
18. 18. The composition according to claim 1, characterized in that the buffering agent is selected from sodium bicarbonate, calcium carbonate, magnesium hydroxide and mixtures thereof.
19. 19. The composition according to claim 1, characterized in that the buffering agent is sodium bicarbonate in an amount from about 0.1 mEq / mg of proton pump inhibitor to about 5 mEq / mg of proton pump inhibitor.
20. The composition according to claim 1, characterized in that the buffering agent is present in an amount of at least about 5 μg / mg.
21. The composition according to claim 1, characterized in that the buffering agent is present in an amount of at least about 10 mEq / mg.
22. 22. The composition according to claim 1, characterized in that the buffering agent is present in an amount of about 5-40 mEq / mg.
23. 23. The composition according to claim 1, characterized in that it comprises from about 200 to about 3000 mg of buffering agent.
24. 24. The composition according to claim 1, characterized in that it comprises about 1000 to about 2000 mg of buffering agent.
25. 25. The composition according to claim 1, characterized in that the non-steroidal antiinflammatory drug is selected from the group consisting of: aminoarylcarboxylic acid derivatives, arylacetic acid derivatives, arylbutyric acid derivatives, arylcarboxylic acid derivatives, arylpropionic acid derivative , pyrazoles derived from salicylic acid, thiazinecarboxamides, epsilon-acetamidocaproic acid, s-adenosylmethionine, 3-amino-4-hydroxybutyric acid, amixetrin, bendazac, benzidamine, α-bisabolol, bucololoma, diphenpiramide, ditazole, emorfazone, fepradinol, guayazulene, nabumetone , nimesulide, oxaceprol, paraniline, perisoxal, proquazone, tenidap, zilenton, and cyclooxygenase-II inhibitors; or a free base, free acid, hydrate salt, ester, amide, enantiomer, isomer, tautomer, polymorph, or prodrug thereof.
26. 26. The composition according to claim 25, characterized in that the non-steroidal anti-inflammatory drug is a non-steroidal anti-inflammatory drug with prolonged action.
27. 27. The composition according to claim 26, characterized by the non-steroidal anti-inflammatory drug of prolonged action is chosen from naproxen sodium, flurobiprofen, ketoprofen, oxapriozin, indometacin, cetoralac, nabumetone, mefenamic, piroxicam, and inhibitors of cixlooxigenasa-II; or a free base, free acid, salt, hydrate, ester, amide, enantiomer, isomer, tautomer, polymorph, or prodrug thereof.
28. 28. The composition according to claim 25, characterized by non-steroidal anti-inflammatory drug is chosen from diclofenac, etodolac, fenoprofen, oral fluorbiprofen, ibuprofen aspirin, aspirin sachet, paracetamol, mornifluato, tramadol, cetoralac, indomethacin, ketoprofen, meclofenamate, meloxicam, nabumetone, naproxen, magnesium trisalicylate hill, oxaprozin, piroxicam, tohnetin, diflunisai, nabumentone, etodalac, flocafenin, sulindac, tenoxicam, thiaprofenic acid, mefenamic acid, diclofenac, aceclofenac, morniflumate, diflunisai, salsalate, valdecoxib, celecoxib, and rofecoxib; or a free base, free acid, salt, hydrate, ester, amide, enantiomer, isomer, tautomer, polymorph, or prodrug thereof.
29. 29. The composition according to claim 25, characterized by the cyclooxygenase-II inhibitor is Celecoxib, Vioxx, Relafen, Lodine, Voltaren, or a free base, free acid, salt, hydrate, ester, amide, enantiomer, isomer, tautomer, polymorph, or prodrug thereof.
30. 30. The composition according to claim 25, characterized in that the aminoarylcarboxylic acid derivative is enfenamic acid, etofenamate, flufenamic acid, isonixin, meclofenamic acid, mefenamic acid, niflumic acid, talniflumate, terofenamate, tolfenamic acid, or a free base, free acid, salt, hydrate, ester, amide, enantiomer, isomer, tautomer, polymorph, or prodrug thereof.
31. 31. The composition according to claim 25, characterized by the aryl acetic acid derivative is aceclofenac, acemetacin, alclofenac, amfenac, amtolmetin guacil, bromfenac, bufexamac, cinmetacin, clopirac, diclofenac sodium, etodolac, felbinac, fenclozic acid, fentiazac , glucametacin, ibufenac, indomethacin, isofezolac isoxepac, lonazolac, metyazinic acid, mofezolac, oxametacin, pyrazolac, proglumetacin, sulindac, thiaramide, tolmetin, tropesin, zomepirac, or a free base, free acid, salt, hydrate, ester, amide, enantiomer , isomer, tautomer, polymorph, or prodrug thereof.
32. 32. The composition according to claim 25, characterized in that the arylbutyric acid derivative is bumadizon, butibufen, fenbufen, xenbucin, or a free base, free acid, salt, hydrate, ester, amide, enantiomer, isomer, tautomer, polymorph , or prodroga of the same.
33. 33. The composition according to claim 25, characterized in that the arylcarboxylic acid is clidanac, ketorolac, tinoridine, or a free base, free acid, salt, hydrate, ester, amide, enantiomer, isomer, tautomer, polymorph, or prodrug thereof.
34. 34. The composition according to claim 25, characterized by the arylpropionic acid derivative is aminoprofen, benoxaprofin, bermoprofen, bucilloxic acid, carprofen, fenoprofen, flunoxaprofen, flurbiprofen, ibuprofen, ibuproxam, indoprofen, ketoprofen, loxoprofen, naproxen, oxaprozin, picetoprofin, pirprofen, pranoprofen, suprofen protizinic acid, thiaprofenic acid, ximoprofen, zaltoprofen, or a free base, free acid, salt, hydrate, ester, amide, enantiomer, isomer, tautomer, polymorph, or prodrug thereof.
35. 35. The composition according to claim 25, characterized by the pyrazole is diphenamizole epirozole, or a free base, free acid, salt, hydrate, ester, amide, enantiomer, isomer, tautomer, polymorph, or prodrug thereof; the pyrazolone is apazone, benzpiperilon, feprazone, mofebutazone, morazone, oxyphenbutazone, phenylbutazone, pipebuzone, propifenazone, prostaglandins, ramifenazone, suxibuzone, thiazolinobutazone, or a free base, free acid, salt, hydrate, ester, amide, enantiomer, isomer, tautomer , polymorph, or prodrug thereof; and the zincarboxamide is ampiroxicam, droxicam, isoxicam, lomoxicam, piroxicam, tenoxicam, or a free base, free acid, salt, hydrate, ester, amide, enantiomer, isomer, tautomer, polymorph, or prodrug thereof.
36. 36. The composition according to claim 25, characterized by the salicylic acid derivative is acetaminosalol, aspirin, benorilate, bromosaligenin, calcium acetylsalicylate, diflunisai, ethersalate, fendosal, gentisic acid, glycol salicylate, imidazole salicylate, lysine acetylsalicylate, mesalamine , morpholine salicylate, 1-naphthyl salicylate, olsalazine, parsalmide, phenyl acetylsalicylate, phenyl salicylate, salacetamide, salicylamide o-acetic acid, salicylsulfuric acid, salsalate, sulfasalazine, or a free base, free acid, salt, hydrate, ester, amide, enantiomer, isomer, tautomer, polymorph, or prodrug thereof.
37. 37. The composition according to claim 1, characterized in that the composition is in a selected dosage form of a powder, a tablet, a disintegrating tablet when biting, a chewable tablet, a coated tablet, a capsule, an effervescent powder , a rapid disintegration tablet or an aqueous suspension produced from the powder.
38. 38. The composition according to claim 1, characterized in that it further comprises one or more excipients selected from the group consisting of activators of parietal cells, erosion facilitators, flavoring agents, sweetening agents, diffusion facilitators, antioxidants and carrier materials selected from binders, suspending agents, disintegrating agents, fillers, surfactants, solubilizers, stabilizers, lubricants, wetting agents, diluents, anti-adherents, and antifoaming agents.
39. 39. A method for treating a disorder related to gastric acids and treating an inflammatory disorder in a subject by administering: (a) a therapeutically effective amount of at least one labile acid proton pump inhibitor; (b) at least one buffering agent in an amount sufficient to increase the pH of gastric fluid to a pH that prevents acidic degradation of at least some of the proton pump inhibitor in the gastric fluid; and (c) a therapeutically effective amount of at least one non-steroidal anti-inflammatory drug.
40. 40. The method according to claim 39, characterized in that the pharmaceutical composition is formulated for delivery to the stomach of at least some of the proton pump inhibitor.
41. 41. The method according to claim 40, characterized in that the disorder related to gastric acid is duodenal ulcer disease, gastric ulcer disease, gastroesophageal reflux disease (GERD), erosive esophagitis, gastroesophageal reflux disease symptomatic of poor response, pathological gastrointestinal hypersecretory disease, Zollinger Ellison syndrome, heartburn, esophageal disorder and acid dyspepsia.
42. 42. The method according to claim 40, characterized in that the inflammatory disorder is chosen from * reperfusion injury to an ischemic organ, myocardial infarction, inflammatory bowel disease, rheumatoid arthritis, osteoarthritis, psoriasis, rejection of organ transplantation, inflammation of the eye , ear, throat, nose or skin, organ observation, male or female sexual dysfunction, radiation-induced injury, asthma, respiratory disorder, metastasis, influenza, incontinence, stroke, heartburn, trauma, acute pancreatitis, pyelonephritis, hepatitis, an autoimmune disease, immune disorder, senile dementia, insulin-dependent diabetes mellitus, disseminated intramuscular coagulation, fat embolism, Alzheimer's disease, adult or infant respiratory disease, carcinogenesis in a neonate, hemorrhage in a neonate, restenosis, atherogenesis, angina, ischemic disease, congestive heart failure or pulmonary edema r, associated with acute myocardial infarction, thrombosis, hypertension, platelet aggregation, platelet adhesion, proliferation of smooth muscle cells, vascular complications associated with the use of medical devices, injuries associated with the use of medical devices and cerebrovascular ischemic events and similar.
43. 43. The method according to claim 40, characterized in that the proton pump inhibitor treats an episode of disorder related to gastric acid.
44. 44. The method according to claim 40, characterized in that the proton pump inhibitor treats a drug-related gastric acid-related disorder.
45. 45. The method according to claim 44, characterized in that the treatment of a disorder related to gastric acid induced by medicament includes the prevention of a disorder related to gastric acid induced by medicament.
46. 46. A method for treating a disorder related to gastric acid and reducing the risk of cardiovascular disease in a subject by administering a composition comprising: (a) a therapeutically effective amount of at least one labile acid proton pump inhibitor; (b) at least one buffering agent in an amount sufficient to increase the pH of gastric fluid to a pH that prevents acidic degradation of at least some of the proton pump inhibitor in the gastric fluid; and (c) a therapeutically effective amount of at least one non-steroidal anti-inflammatory drug.
47. 47. The method according to claim 46, characterized in that the cardiovascular disease is heart attack or stroke.
48. 48. A method for treating a disorder related to gastric acid and reducing the risk of cancer in a subject by administering a composition comprising: (a) a therapeutically effective amount of at least one labile acid proton pump inhibitor; (b) at least one buffering agent in an amount sufficient to increase the pH of gastric fluid to a pH that prevents acidic degradation of at least some of the proton pump inhibitor in the gastric fluid; and (c) a therapeutically effective amount of at least one non-steroidal anti-inflammatory drug.
49. 49. The method according to claim 48, characterized in that the cancer is chosen from esophageal cancer, lung cancer, colorectal cancer, breast cancer and prostate cancer.
50. 50. A method for protecting against esophageal disorder or esophageal damage in a subject, by administering a composition comprising: (a) a therapeutically effective amount of at least one labile acid proton pump inhibitor; (b) at least one buffering agent in an amount sufficient to increase the pH of gastric fluid to a pH that prevents acidic degradation of at least some of the proton pump inhibitor in the gastric fluid; and (c) a therapeutically effective amount of at least one non-steroidal anti-inflammatory drug.
51. 51. A method for treating a disorder related to gastric acid and treating a chronic inflammatory disorder in a subject, by administering: (a) a therapeutically effective amount of at least one labile acid proton pump inhibitor; (b) at least one buffering agent in an amount sufficient to increase the pH of gastric fluid to a pH that prevents acidic degradation of at least some of the proton pump inhibitor in the gastric fluid; and (c) a therapeutically effective amount of at least one non-steroidal anti-inflammatory drug.
52. 52. A method for treating a disorder related to gastric acid and treating an inflammatory disorder in a subject by administering to it: (a) a first pharmaceutical composition comprising: (i) a therapeutically effective amount of at least one proton pump inhibitor labile acid; and (ii) at least one buffering agent in an amount sufficient to increase the pH of gastric fluid to a pH that prevents acidic degradation of at least some of the proton pump inhibitor in the gastric fluid; and (b) a second pharmaceutical composition, comprising a therapeutically effective amount of at least one non-steroidal anti-inflammatory drug.