MXPA06007010A - Oral medicament delivery system comprising collagen-based fibrous matrix - Google Patents

Abstract

Oral medicament delivery system comprising a pharmaceutical composition (60) comprising a flexible matrix, said matrix formed of a plurality of fibers comprising a collagen-based carrier (44) and a medicament (59), the composition (60) orally dissolvable to deliver a unit dose of the medicament (50) to a patient. The flexible composition (60) can be dose titrated and co-administered with a second pharmaceutical formulation.

Description

ORAL MEDICATION SUPPLY SYSTEM BACKGROUND OF THE INVENTION FIELD OF THE INVENTION The present invention relates to an oral drug delivery system and, in particular, to a fibrous composition for orally delivering a medicament to a patient.

DESCRIPTION OF THE PREVIOUS TECHNIQUE A common method of delivering a medication to a patient is through the oral cavity. Commonly used orally administrable formulations include solid formulations such as tablets, pills, capsules, dispersible oral pills, dragees, troches, lozenges and the like. However, the administration of drugs via solid formulations presents challenges and drawbacks for a portion of the patient population. Statistically, at least 20 percent of the population finds it difficult to swallow the solid oral formulations of the medications and, consequently, avoid ingesting these formulations. In addition, about 10 percent of women are completely unable to swallow intact tablets, pills and capsules, without cutting them into smaller pieces. Patients generally resist or avoid swallowing a solid formulation of medication, particularly when the act of swallowing is problematic for the individual. Complications such as global hysteria and / or drowning due to pharyngeal and esophageal motility problems, usually make it painful to swallow for a patient. In addition, in patients with pharyngitis and / or a pharynx markedly inflamed or severely irritated in another way, such as due to a bacterial infection, it often makes it impossible for the patient to swallow. Chronic disorders and other conditions, such as psychological and / or psychosomatic aversion to the act of swallowing, or a fear of drowning with pills or tablets, make patients more reluctant to swallow medications formulated as non-chewable solids. Patients may also be reluctant to swallow medications in solid formulations due to their physical properties, including size, shape and / or taste, or simply by a personal choice not to swallow and / or ingest the formulation. Members of the population of pediatric patients are reluctant to swallow solid formulations of medications for additional reasons. In particular, young children usually do not like to take pills, tablets and other "medicines". Additionally, children generally reject oral ingestion of medication during periods of illness. In addition, children are generally more inclined to chew the pills or tablets than to swallow them, typically experiencing a bitter taste in the mouth that often causes children to spit or reject the formulation and refuse to ingest it in some other way. Also, many of the available pills and tablets are notched in half only and do not come in smaller ones, such as thirds or quarters, making it difficult, and sometimes impossible, to dose pediatric medications. Accordingly, the child should swallow a larger portion of the solid medications to obtain the prescribed dose and / or recommended by the physician. Finally, it is even more difficult to co-administer a second solid formulation, which may be necessary to provide a specific benefit such as improving the dose of the first medication, to a child with physical and / or mental aversion to swallowing a solid, non-chewable medication. More recently, chewable and soluble forms of a medication have been proposed. For example, each of US Patent Nos. 4,855,326, 4,997,856, 5,034,421, and 5,096,492, describe a flowable type of pharmaceutical composition that has a sugar-based carrier or a carrier with an oily combination with sugar to deliver a drug to a patient. patient. However, due to the physical properties of the carrier materials, it was found that these compositions were not very stable for long periods of time. Particularly, being susceptible to the moisture degrading effects, those formulations have not been extremely successful and / or extensively marketed. More specifically, it was found that many medications were not stable with these carriers, thereby raising the costs associated with that medication. However, patients, whether children or adults, under a medication regimen and / or simply with the need for the therapeutic benefits of a medication, should be administered, or self-administered, the dosage formulation. Therefore, there is a need to provide a better method for orally administering a medicament to a patient. There is furthermore a need to orally administer the medicaments in a manner which contemplates the resistance and / or the aversion of the patient to swallowing and / or ingesting a medicament formulation. There is also a need to improve the patient's ingestion of the medication according to a medication regimen and, in particular, to improve the approach for pediatric patients. And further, there is a need to provide a formulation of the drug that provides stability for a wide variety of drugs.

BRIEF DESCRIPTION OF THE INVENTION The present invention provides an oral drug delivery system comprising a fibrous pharmaceutical composition, for the oral delivery of a medicament to a patient. The delivery system contemplates the weaknesses and drawbacks associated with the previously proposed oral drug delivery formulations and, in particular, considers the drawbacks associated with the solid formulations of medicament previously proposed and commonly used. Particularly, the delivery system considers the problems associated with the swallowing of conventional pills, tablets and other solid drug formulations, as described in the background section of the invention. Additionally, the delivery system contemplates the drawbacks associated with sugar-based fluids as carriers for the drugs. In addition, the pharmaceutical compositions, as part of the delivery system, do not look like a pill or a tablet, but have a microscopically fibrous appearance and structure, which makes the membrane adhesive composition flexible and orally soluble and, therefore, more acceptable and desirable for adult patients and not expectorable by pediatric patients. In addition, this form of dose delivery can be torn, cut or shredded with scissors to produce smaller dosage forms, e.g. eg, halves, rooms or other sizes. The pharmaceutical composition in the oral medication delivery system comprises a matrix formed of fibers, wherein some or all of the fibers include a collagen-based carrier and a medicament. The fibrous matrix is capable of partially or completely dissolving in the oral cavity to supply the patient with a dose of the drug, transmucosally or via the intestine. The basic unit of the composition containing the medicament is a fiber, cord or filament, as opposed to the particles and / or the granules with micron size in conventional compacted tablets under pressure. The fiber in the compositions is based on collagen, i. e., is formed mainly of collagen protein, and the medicine is incorporated in it or distributed in it in various modalities. Therefore, the collagen-based fiber serves as a carrier or vehicle to deliver the medicament. Collagen provides many benefits as a carrier. Specifically, collagen has proven to be successful in many body applications. Collagen is also capable of agglutinating and carrying active-loaded pharmaceutical ingredients (APIs). Collagen is relatively inexpensive, readily available and its purity and sterility can be controlled. Collagen can withstand aseptic processing techniques at temperate temperatures in the range of about 20 ° C to about 35 ° C, which many API's can withstand without decomposition. In the embodiments of the invention, the medicament may be distributed in, or incorporated into, each fiber or a selected fiber group, and may be any compound that provides a biological and / or therapeutic benefit to the patient. Thus, exemplary drugs include, without limitation, active pharmaceutical ingredients (API) and non-active ingredients, such as vitamins, minerals and the like. The amount of the medication is selected as desired, and it generally depends on the particular medication, the accepted dosage practices for that medication, the purpose of administration, and the target population of patients. The amount of medicament may also depend on the amount by weight of the carrier fiber and its natural porosity and absorption nature. This dependency allows the composition to be administered in a dose that can be dosed and / or generally supervised, according to the recommended dose. In one embodiment, the composition, or individual fibers, they also include excipients to provide desirable aesthetic, physical and / or chemical properties to the orally administrable composition. For example, soluble excipients including water-soluble substances, including salts or basic regulators, which generally dissolve in saliva (moderately acidic) or in fluids containing water in the oral cavity may be included in the composition. Simple sugars and combinations thereof, including monosaccharides, disaccharides and polysaccharides and other sweeteners, generally provide a sweet taste, thereby making the composition more palatable to children. Flavor-masking components may also be added to improve the taste and / or remedy the offensive bitter remnants by chewing and / or ingesting various broken or cut tablets, pills and capsules, which would otherwise be intended to be chewed. The embodiments of the composition may also include a bioadhesive or a mucoadhesive to adhere the composition to the buccal mucosa of the patient. This adhesion allows the composition to be exposed for a period of time, while retained in the oral mucous membrane, for the appropriate dissolution conditions, thereby dissolving the composition over time and providing a delayed release effect to supply the composition. medication to the patient. Additionally, a mucoadhesive is advantageous for drugs that are more effective when absorbed through the mucous membrane, thereby deviating the first effects of hepatic passage. The composition of the drug delivery system is manufactured using non-spoonable, non-melting methods, and is fibrous in nature, formed from a flexible fiber matrix. The matrix can be formatted in any suitable or desirable form for oral ingestion. For example, the composition can exist in a circular shape similar to a coin the size of one ten or twenty-five cents (dime or quarter). Also contemplated is a spindle shape, i.e., an elongated shape having a thick or broad central region and thin terminal regions. Generally, the most desirable forms can be prepared by: (1) forming fiber sheets, stacking multiple sheets on top of each other to form layers, and then compacting and compressing these layers in a single form, or (2) by emptying the solutions in the matrix collagen material, with or without the added medication, allowing the collagen to form a fibrous gel matrix, then dehydrating, pressing, cutting with die or processing the gel in another way. The composition can also be marked to indicate a dosing time and / or a program, and / or perforated or indented so that it is easily divisible. The fibrous nature of the composition provides advantages over pills, tablets, capsules, oral dispersion forms (e.g., "meltable tablets" and other conventional oral solid dosage formulations.) Particularly, it allows the composition to be easily cut and fragmented , unlike most conventional tablets, pills and capsules, this benefit provides the ability to dose and / or monitor the dose that is administered to the patient.The chewable and soluble nature of the composition makes it more friendly to be ingested by The pediatric patients, who may otherwise be psychologically and / or physically reluctant to swallow a conventional solid dosage formulation, furthermore, according to another aspect of the invention, the flexibility of the fibrous matrix allows the composition to be wrapped around of other dosage formulations, such as pills or tablets, for the co-administration of multiple medications to a patient. For example, the fibrous matrix contains one or more API's, while a pill or tablet, or another dose wrapped in it, include other different APIs. Alternatively, the fibrous matrix includes an API for rapid delivery and a solid dose wrapped therein includes the same API or a similar one for a more delayed release. In another embodiment, the compositions having mucoadhesive properties also prevent the pediatric patient, the non-cooperative patient, and / or the protesting patient from spitting the composition. In addition, unlike dispersible oral tablets, such as Zydis® and other formulations, the present fibrous composition is not limited API dose. The present invention also provides methods for forming the composition containing the medicament and methods for administering it to a patient. The composition can be administered directly, by placing it in the patient's oral cavity, or indirectly, for example, by suspending or dissolving it first in an amount of a liquid, such as water, juice or other beverage chosen by the patient, in a spoon, glass , cup or other container of your choice. In any method, the composition dissolves and disperses the medication in the liquid (or saliva) before the patient ingests it. Conventional pills and tablets usually do not dissolve in saliva or in a chosen liquid. Accordingly, the oral drug delivery system of the present invention stimulates the ingestion of a medicament, in compliance with a medication regimen. Particularly, the composition in liquid form is easily swallowed and is not usually retained and spit out of the mouth. In this way, the present invention also improves compliance in psychiatric patients and / or other non-cooperative patients.

BRIEF DESCRIPTION OF THE DRAWINGS The attached drawings, which are incorporated in and constitute a part of this specification, illustrate the modalities of the invention and, together with a general description of the invention given above, and a detailed description of the modalities given. below, they serve to explain the principles of the invention. Figure 1 is an example form of the pharmaceutical composition in the present invention; Figure 2 is a second example form of the pharmaceutical composition in the present invention; Figures 3A-3F illustrate a first exemplary method for making the collagen-based composition containing the medicament of the present invention. Figure 4 is a perspective, in schematic view, of the product made through the example method illustrated in Figures 3A-3F; Figure 5 is a perspective view of the compressed product made through the example method illustrated in Figures 3A-3F; Figure 6 illustrates a second exemplary method for making the collagen-based composition containing the medicament of the present invention; and Figure 7 is a partial sectional view of the product made through the example method illustrated in Figure 6.

DETAILED DESCRIPTION OF THE PREFERRED MODALITIES The present invention will be better appreciated in view of the following definitions: The term "system", with respect to the delivery of a medicament, is generally intended to refer to one or more compositions that are delivered to the patient. Therefore, this term contemplates the provision of a single pharmaceutical composition, such as a fibrous composition alone, or a combination of pharmaceutical formulations, such as the fibrous composition with one or more other formulations, which are administered simultaneously or sequentially one after the other. of the other. The term "matrix", as used herein, is intended to refer generally to a web or network of fibers, strands or filament-like structures. For example, the fibers may be interlaced, cross-linked, or arranged with any other orientation in relation to each other to form a matrix, as appreciated by one of ordinary skill in the art. The term "collagen-based", as used herein with reference to the composition of the carrier, is intended to refer generally to a material that is composed primarily of a collagen form. Therefore, this term contemplates 100% of collagen carrier, and also carriers that have at least 50% by weight of a collagen material. This term also covers all forms of collagen, natural or synthetic, including homopolymers, cross-linked polymers (tropocollagen), copolymers and collagen strands, as well as collagen-type proteins. Accordingly, this term also encompasses chemically modified collagen, formed by synthetic methods such as by replacing one or more of the amino acids in the protein's main collagen element, or by modifying the side chain (s) (is) of the polymer (s). The term "carrier", as used herein, is intended to refer generally to a vehicle or substrate for delivering the medicament to the patient. The term "medicament", as used herein, is intended to refer generally to any biological substance that has a psychological and / or therapeutic effect on a patient, for example, the term "medicament" encompasses all active pharmaceutical ingredients (APIs), the ingredients non-active, including vitamins, minerals, dietary components, and the like The term also encompasses compounds, which are administered for their therapeutic and / or prophylactic effects.The terms "orally soluble" and "orally dispersible", as herein used in reference to the composition, they are intended to refer generally to decomposition, up to and including a complete dissolution of the composition., this term includes compositions that decompose or dissolve, partially or totally, in a particular medium such as saliva, or in aqueous liquids and foods, present in the oral cavity. As such, this term encompasses all compositions, which will generally dissolve in the oral environment stimulated with liquid or other substance to generate the secretion of saliva. The present invention provides an oral drug delivery system comprising a fibrous pharmaceutical composition, and also provides methods for orally delivering a medicament to a patient. The pharmaceutical composition is generally a fibrous matrix formed of a plurality of fibers. The composition is sufficiently soluble in the oral cavity to supply the patient with a unit dose of the drug to the oral mucous membrane, or to the intestine via ingestion. Each fiber can generally serve as a carrier to deliver the one or more drugs to the patient's oral cavity. The carrier is generally formed of collagen or a collagen-based material. Collagen is a naturally occurring fibrous protein formed of fibers that have a high tensile strength, and whose solubility in an aqueous and organic medium, such as alcohol and ether, varies depending on the particular structure and shape of the collagen. Collagen provides many benefits as a carrier. Particularly, collagen has been used successfully in applications and physiological applications, including use as implants and hemostatic agents in the medical industry, as topical agents in the cosmetic industry, and as digestible products in the food industry. Collagen can possibly be loaded thereby improving its ability to bind and / or carry loaded medicaments, and particularly active pharmaceutical ingredients (API). Collagen is relatively inexpensive and readily available in a multitude of sources and raw materials and, therefore, provides a low cost base material relative to many other formulation materials. In addition, the purity of the collagen can be controlled. In addition, the processing of collagen takes it to the pharmaceutical formulation through passing through aseptic techniques and being easily processed at temperate temperatures in the range of about 20 ° C to about 35 ° C. This ambient temperature allows the inclusion of many API's without the risk of degradation and / or chemical decomposition, which would otherwise result from exposure to higher temperatures. Collagen is also a suitable candidate for extrusion for the carrier material of the drug. Once in solution, the collagen can be easily extracted from its solvent liquid and extruded to form strands or fibrous cords that dry and solidify quickly. Alternatively, the collagen in solution can be induced to form a fibrous gel matrix through a process called reconstitution. These gels can then be processed to produce non-woven fibrous matrices having a highly porous structure. In addition, the physical properties of collagen are desirable.

Specifically, many forms of collagen are hygroscopic and, therefore, soluble in saliva and in most other fluids, and in foods, typically present in the oral cavity. The mechanical and chemical properties of collagen matrices can be varied during processing to control their handling and dissolution properties. This can be achieved through such means as to use various salts, acids or enzymes during the original collagen extraction process, by modifying the extrusion of the gel reconstitution process, or by using cross-linking agents or other treatment methods during the production of the gel. the collagen matrix. Therefore, collagen or a collagen-based material as carrier, provides many particularly useful properties for an orally administrable drug formulation. The amount of collagen in each fiber cord may vary depending on the desired properties of the administrable composition. For example, being hygroscopic, highly porous, and generally soluble in water-based liquids, including saliva, large amounts of collagen-based carrier are not necessary. The amount of collagen may also be based on the amount of the drug (s) carried within or distributed on the fiber, as discussed herein. The medication associated with the fiber, and the composition as a whole, can be selected as desired. Suitable medications include active pharmaceutical ingredients (APIs). For example, the drug can be any of the following API's, many of which are well-known drugs: Anti-inflammatory analgesic agents, such as acetaminophen, aspirin, salicylic acid, methyl salicylate, choline salicylate, glycol salicylate, 1- menthol, camphor, mefenamic acid, flufenamic acid, indomethacin, diclofenac, alcofenac, ibuprofen, ketoprofen, naproxen, pranoprofen fenoprofen, sulindac, fenbufen, cyidanac, flurbiprofen, indoprofen, proticidic acid, fentiazac, tolmetin, tiaprofenic acid, bendazaco, bufexamac, piroxicam, phenylbutazone, oxyphenbutazone, clofezone, pentazocine, mepirrizola, and the like; Drugs that have an action on the central nervous system, for example sedative agents, hypnotic agents, anti-anxiety agents, analgesic and anesthetic agents, such as doral, buprenorphine, naloxone, haloperidol, flufenacin, pentobarbital, phenobarbital, secobarbital, amobarbital, cidobarbital, codeine , lidocaine, tetracaine, dyclonine, dibucaine, cocaine, procaine, mepivacaine, bupivacaine, etidocaine, prilocaine, benzocaine, fentanyl, nicotine, morphine, codeine, hydrocodone, hydromorphone, diacetylmorphine, methadone, sufentanil, meperidine, levodromorane, and the like. Antihistaminic or anti-allergenic agents such as diphenhydramine, dimenhydrinate, perphenazine, tripolidine, pyrilamine, chlorcyclicin, promethazine, carbinoxamine, tripelenamine, bronfenyramine, hydroxycin, cyclin, medicine, chlorprenaline, terfenadine, chlorpheniramine, phenylpropanolamine, phenylephrine, atropine, hyoscyamine, cyproheptidine, and the like; Anti-inflammatory agents including steroids, such as hydrocortisone, cortisone, dexamethasone, fluocinolone, triamcinolone, medrisone, prednisolone, flurandrenolide, prednisone, haicinonide, methylprednisolone, fludrocortisone, corticosterone, parametasone, betamethasone, ibuprofen, naproxen, fenoprofen, fenbufen, flurbiprofen, indoprofen, ketoprofen , suprofen, indomethacin, piroxicam, aspirin, salicylic acid, diflunisal, methyl salicylate, phenylbutazone, sulindac, mefenamic acid, sodium meclofenamate, tolmetin, androgenic steroids such as testosterone, methyltestosterone, fluoxymesterone, estrogens such as conjugated estrogens, esterified estrogens, estropipate, 17-beta estradiol, 17-beta estradiol valeriato, equilin, mestranol, estrone, estriol, 17-beta ethinyl estradiol, and diethylstilbestrol; progestational agents such as progesterone, 19-norprogesterone, norethindrone, norethindrone acetate, melengestrol, chlormadinone, ethisterone, medroxyprogesterone acetate, hydroxyprogesterone caproate, ethinodiol diacetate, norethynodrel, 17-alpha hydroxyprogesterone, dydrogesterone, dimetisterone, ethinylstanren, norgestrel, demegestone , promegestone, megestrol acetate, and the like; Respiratory agents such as theophylline and beta2 adrenergic agonists such as albuterol, terbutaline, metaproterenol, ritodrine, carbuterol, fenoterol, quinterenol, rimiterol, solmefamol, soterenol, tetroquinol, caffeine, caffeine citrate, and the like; Sympathomimetic agents, such as dopamine, norepinephrine, phenylpropanolamine, phenylephrine, pseudoephedrine, amphetamine, propylhexedrine, arecoline, and the like; Local anesthetic agents, such as benzocaine, prilocaine, bupivocaine, procaine, dibucaine, lidocaine, and the like; Antimicrobial agents including antibacterial agents, antifungal agents, antifungal agents and antiviral agents; tetracyclines, such as oxytetracycline; penicillins such as ampicillin; cephalosporins such as cephalothin; aminoglycosides such as kanamycin; macrolides such as erythromycin, chloramphenicol, iodides, nitrofrantoin, nystatin, amphotericin, fradiomycin, sulfonamides, purrolnitrin, clotrimazole, miconazole, chloramphenicol, sulfacetamide, sulfamethacin, sulfadiazine, sulfamerazine, sulfametizole and sulfisoxazole; antivirals, including idoxuridine; clarithromycin; and other anti-infectives including nitrofurazone, and the like; Hypertensive agents such as clonidine, alpha-methyldopa, reserpine, sirosingopine, rescinamine, cinnarcin, hydrazine, prazocin, ACE inhibitors, propanolol, pindolol, labetalol, clonidine, captopril, enalapril, lisonopril, and the like; Antihypertensive diuretics such as chlorothiazide, hydrochlorothrazide, bendoflumethacide, trichlormethiazide, furosemide, triparnide, methylclothiazide, penflucide, hydrothiazide, spironolactone, metolazone, and the like; Cardiotonic agents such as digitalis, ubidecarenone, dopamine, and the like; Coronary vasodilators such as organic nitrates, including, without limitation, nitroglycerin, isosorbitol dinitrate, erythritol tetranitrate, pentaerythritol tetranitrate, dipridamole, dilacep, trapidyl, trimethocidine, and the like; Vasoconstrictors, such as dihydroergotamine, dihydroergotoxin, and the like; Beta-blockers or antiarrhythmic agents, such as timolol pindolol, propranolol, and the like; Calcium antagonists and other circulatory organ agents including, without limitation, apriplex, diltiazene, nifedipine, nicardipine, verapamil, benciclan, ifenprodil tartarate, molsidomine, clonidine, prazosin, and the like; Anticonvulsant agents such as nitracepan, meprobamate, phenobarbitol, carbomacepin, valprolco acid, oxacepin, phenytoin, and the like; Agents for dizziness and nausea, such as isoprenaline, betahistine, scopolamine, and the like; Tranquilizing agents such as reserpine and chlorpromazine; and anti-anxiety benzodiazepines, such as alprazole, chlordiazepoxide, chloraceptato, halacepán, oxacepán, pracepán, clonacepán, fluracepán, trialozan, loracepán, diacepán, and similars; Antisychotic agents such as butyrophenones and phenothiazines including, without limitation, thiopropazate, chlorpromazine, triflupromazine, mesoridazine, piperracitazine thioridazine, acetophenazine, flufenazine, perphenazine, trifluoperazine, and other major tranquilizers such as chlorpratixene, thiothixene, haloperidol, bromperidol, loxapine, and molindone, as well as those agents used at lower doses in the treatment of nausea, vomiting, and the like; Muscle relaxants, such as tolperisone, baclofen, dantrolene sodium, cyclobenzaprine, and the like; Drugs for Parkinson's disease, spasticity and acute muscle spasms, such as levodopa, carbidopa, amantadine, apomorphine, bromocriptine, selegiline (deprenyl), trihexyphenidyl hydrochloride, benztropine mesylate, procyclidine hydrochloride, baclofen, diacepan, dantrolene, and the like; Respiratory agents and cough suppressants such as codeine, ephedrine, isoproterenol, dextromethorphan, orciprenaline, ipratropium bromide, chromic acid, and the like; Hormones or non-steroidal antihormones such as corticotropin, oxytocin, vasopressin, salivary hormone, thyroid hormone, adrenal hormone, kallikrein, insulin, oxendolone, and the like; Antitumor agents such as 5-fluorouracil and derivatives thereof, crestin, picibanil, ancitabine, cytarabine, and the like; Enzymes, such as lysozyme, urokinase, and the like; Herbal medicines or crude extracts such as glycyrrhiza, aloe, Sikon (Lithospermi Radix), and the like; Miotic agents, such as pilocarpine, and the like; Chlorgenic agonists such as choline, acetylcholine, methacholine, carbachol, bethanechol, pilocarpine, muscarine, arecoline, and the like; Chlorigenic antimuscarinic or muscarinic blocking agents such as atropine, scopolamine, homatropine, methanscopolamine, homatropine methyl bromide, methantheline, cyclopentolate, tropicamide, propantheline, anisotropin, dicyclomine, eucatropine, and the like; Mydriatic agents such as atropine, cyclopentolate, homatropine, scopolamine, tropicamide, eucatropine, hydroxyamfetamine, and the like; Psychic energizers such as 3- (2-aminopropyl) indole, 3- (2-aminobutyl) indole, and the like; Humoral agents such as prostaglandidins, natural and synthetic, for example, PGE-i, PGE2alpha, and PGF2alpha, and the analogous misoprostol of PGE-; Antispasmodic agents such as atropine, methantheline, papaverine, cinnaminine, methylcopolamine, and the like; Antidepressant agents such as isocarbazine, phenelzine, tranylcypromine, imipramine, amitriptyline, trimipramine, doxepin, desipramine, nortriptyline, protriptyline, amoxapine, maprotiline, trazodone, and the like; Antidiabetic agents such as insulin, and anticancer drugs such as tamoxifen, methotrexate, and the like; Anorectic drugs such as dextroamphetamine, methamphetamine, phenylpropanolamine, fenfluramine, diethylpropione, macindola, phentermine, and the like; Antiallergenic agents such as antazoline, metaprilene, chlorpheniramine, pyrilamine, pheniramine, and the like; Decongestant agents such as phenylephrine, ephedrine, naphazoline, tetrahydrozoline, and the like; Antipyretic agents, such as aspirin, salicylamide, and the like; Antimigraine agents such as dihydroergotamine, pizotiiin, triptans, and the like; Antimalarial agents such as 4-aminoquinolines, alpha-aminoquinolines, chloroquine, pyrimethamine, and the like; Anti-ulcer agents such as misoprostol, omeprazole, emprostil, and the like; Peptides such as growth-releasing factor, and the like; Antiestrogen or antihormone agents, such as tamoxifen or human chorionic gonadotropin, and the like; and Antiulcer agents such as allantoin, aldioxa, alcloxa, methylscopolamine methylisulfate, and the like.

The medications and the example drugs listed above can be used individually or in combination, as required. In addition, the drugs can be used either in their free base form or, if capable of forming salts, in the form of a salt with a suitable counter, such as a suitable acid or base. Suitable acidic counter ions include, without limitation, organic acids such as: methane sulphonic acid, toluene sulfonic acid, lactic acid, tartaric acid, fumaric acid, maleic acid, succinic acid, acetic acid and the like, and inorganic acids, such as, hydrochloric acid, hydrobromic acid, hydrofluoric acid, phosphoric acid, sulfuric acid, and the like. Suitable basic counter ions include, without limitation, organic bases such as alkyl amines including triethylamine, and the like, inorganic bases, such as sodium hydroxide, potassium hydroxide, lithium hydroxide, calcium hydroxide, ammonia and the like. If the drug has a carboxylic acid functional group, then acid derivatives, such as an ester, an anhydride or an amide can be employed. The esters may include alkyl esters, aryl esters, aralkyl esters, and the like, and may also have functional groups capable of forming salts by themselves. The medicine can also be a nutritional ingredient such as a vitamin, a mineral and the like. The term "vitamin", as used herein, includes, without limitation: thiamin, riboflavin, nicotinic acid, pantothenic acid, pyridoxine, biotin, folic acid, vitamin B6, vitamin B12, lipoic acid, ascorbic acid, vitamin A, vitamin D, vitamin E, vitamin K and derivatives thereof, calciferoles, mecobalamin, and the like. Coenzymes are also included within the term "vitamin", since coenzymes are generally beneficial agents for the body. Coenzymes include thiamine pyrophosphates (TPP), flavin mononucleotides (FMM), flavindenine dinucleotides (FAD), nicotinamide adenine dinucieotides (DNA), nicotinamide adenine dinucleotide phosphate (NADP), coenzyme-A pyridoxal phosphate ( CoA), biocytin, tetrahydrofolic acid, coenzyme B- | 2, lipolisin, 1, 1-cis-retinal, and 1, 2,5-dihydroxycholecalciferol. The term "vitamin" also includes choline, camitina, and alpha, beta and gamma carotenes. Therefore, a vitamin may include, for example, substances that may or may not be required in the diet. Vitamin salts are also suitable. The term "mineral", as used herein, refers to inorganic substances, such as metal compounds and the like, generally required in the diet. Therefore, suitable minerals include, without limitation: calcium, iron, zinc, selenium, copper, iodine, magnesium, phosphorus, chromium and the like, their salts, which are high, and other forms of composition, and combinations thereof. Other nutritional ingredients, commonly called "dietary supplements," include substances that have an appreciable nutritional effect when administered in small amounts. Suitable dietary supplements include, without limitation, ingredients such as bee pollen, bran, wheat germ, seaweed, cod liver oil, ginseng, and fish oils, amino acids, proteins and mixtures thereof. It will be appreciated that dietary supplements can also incorporate vitamins and minerals. The medication can be incorporated into each fiber. For example, each fiber can be formed with the medicament, such as by extrusion or other methods. Alternatively, the drug can be distributed on each fiber or on a collection of fibers, in the composition. For example, individual fibers or a bundle of fibers can be covered with the medicament. The amount of medication included in the formulation will generally depend on the particular medication, its intended use, and the patient's profile. The medication is dosed in accordance with accepted pharmacy and FDA practices and government regulations. For example, drug compositions directed to administration in children will include the medicament in minor amounts such as from 1 mg to about 25 mg, which encompasses the therapeutically effective doses for a majority of pediatric drugs, and dosages generally enough for many medications for adults. Effective dosages are generally those equivalences or amounts of a drug or a pharmaceutically active substance, which are sufficient to obtain the therapeutic response (biological response) required or desired, when administered to a patient. In one embodiment, the composition includes the drug (s) in dosage amounts up to about 1000 g. In another embodiment, the composition includes the medicament (s) in dosage amounts in the range from 25 mg to about 100 mg. In yet another embodiment, the composition includes the drug (s) in dosage amounts up to about 25 mg. Higher doses will generally increase the size of the fibrous matrix. But this is not a disadvantage, since the composition can be dissolved, fragmented and otherwise supplied in a liquid or aqueous medium suitable for the patient's choice. The amount of the drug may also depend on the amount of collagen-based carrier, and vice versa, in the composition. For example, depending on the physical properties and the degree of dispersion and solubility in the desired oral environment, the amounts and ratios of the weights of the carrier to the medicament vary. In one embodiment of the invention, the weight ratio of carrier to medicament in the composition, or in each fiber, is in the range of about 50: 1 to about 1: 50. In another embodiment, the ratio by weight of carrier to medicament is in the range of about 10: up to about 1: 10. In yet another embodiment, the ratio by weight of carrier to medicament is about 1: 1. With reference to a vitamin or mineral, an effective amount is generally at least about 10% of the Recommended Daily Allowance ("RDA") in the United States. For example, an effective amount of vitamin C would include an amount of vitamin C sufficient to provide 10% or more of the RDA. Typically, when the formulation includes a vitamin or mineral, it will incorporate larger amounts, such as close to 100% or more of the applicable RDA. The composition as a whole, each fiber, or a selected collection of fibers, may also include other desirable excipients. The excipients that dissolve in the oral environment are useful. Suitable excipients include, without limitation: carbohydrates, monosaccharides, disaccharides, polysaccharides or simple sugars, sugar derivatives, and the like. Examples of sugars and other suitable excipients include, without limitation: high calorie sugars, such as sucrose, lactose, glucose, d-glucose, I-glucose, maltose, dextrose, fructose, fructose, gentiobiose, cellobiose, panose, maltotriose, maltotetrose, arabinose, mannose, d-mannose, galactose, d-galactose, d-glyceraldehyde, amylose, allose, algae, talose, gulose, iodine, ribose, erythrose, threose, lixose, xylose, d-xylose, rhamnose, inverse sugar , corn sugar, inositol, glycerol, glycogen, pectin, agar, sorbitol, mannitol and combinations thereof; low calorie sugars, such as sucralose, polyols, tagarose, trehalose, xylitol, dextrans, dextrins, dextrates, polysorbates, maltodextrin, xylitol, amylase, amylopectin, ribose, β-maltose, fucose, sialic acid (neuraminic acid), N- acetylgalactosamine, N-acetylglucosamine, pseudoheptulose, ribulose, xylulose and combinations thereof; non-sugar sweeteners, such as acesulfane potassium, aspartame, neotame, saccharin, steveoside and combinations thereof; non-sweetening agents, such as alitame, cyclamate, dihydrochalcones (DHC's), glycyrrhizin, thaumatin, gelatin, glycerin, triacetin, trehalose, alginates, gelling gum, cellulose, microcrystalline cellulose, xanthan gum, cellulose acetate phthalate, hydropropylcellulose, hydropropylmethylcellulose, ethylcellulose , methylcellulose, L-HPC (substituted hydroxypropyl cellulose), carogen, croscarmellose, povidone, crospovidone, starch, sodium starch glycolate, glucan, Adjumer® (polydi [carboxylatophenoxy] phosphazene), Pleurane (glycan), Pluronic 121 (Poloxamer 401), glyceraldehydes, dihydroxyacetone, and combinations thereof; and the carrier / fluid / menses combination, such as, but not limited to, directly compressed dried honey (Hony- ®), lactose and aspartame, lactose and cellulose, microcrystalline cellulose and carogen, microcrystalline cellulose and guar gum, microcrystalline cellulose and sodium carboxymethyl cellulose, microcrystalline cellulose and lactose, and a combination of sugar and starch. Desirable builders including, without limitation, binders, non-effervescent disintegrants, coloring agents, flavors, flavor improvers, taste maskers, oral dispersing agents, stabilizers, preservatives, diluents, fillers, compaction agents, bioadhesives, agents may also be included. of effervescent disintegration, and the like. Examples of binders include acacia, tragacanth, gelatin, starch, cellulose materials such as methyl cellulose and sodium carboxy methyl cellulose, alginic acids and salts thereof, magnesium aluminum silicate, polyethylene glycol, guar gum, polysaccharide acids, bentonites, sugars, inverse sugars, and the like. The binders can generally be used in an amount of up to about 60% by weight, and advantageously from about 10% to about 40% by weight of the total composition. In addition, one or more disintegrants or dispersion improvers can be used to improve the breaking capacity of the composition in an aqueous environment, such as the oral cavity. Disintegrants include starches, such as corn starch, potato starch and modified starches thereof, sweeteners, clays such as bentonite, microcrystalline cellulose (even as surface agents high HLB emulsifiers), purified wool cellulose, alginates, polyvinyl pyrrolidones , gums such as agar, guar, partially hydrolyzed guar gum, carob bean, carayá, kaolin, pecitin, sodium starch glycolate, isoamorph silicate, and tragacanth. The disintegrants can generally comprise up to about 20% by weight, and advantageously between about 2% and about 10% by weight of the final composition. The coloring agents may include titanium oxide, and colorants suitable for foods, such as those known as dyes F.D. & C, and natural coloring agents such as grape skin extract, red beetroot powder, beta-carotene, anato, carmine, turmeric, paprika, etc. The amount of coloring agent (s) used may be in the range of about 0.1% to about 3.5% by weight of the final administrable composition.

The flavors incorporated in the composition can be chosen from among synthetic flavor oils and aromatic flavors and / or natural oils, plant extracts, leaves, flowers, fruits and so on, and combinations thereof. These may include cinnamon oil, wintergreen oil, peppermint oil, clover oil, bay oil, anise oil, eucalyptus, thyme oil, cedar leaf oil, bitter almond oil and cassia oil. Also useful as flavors are vanilla, citrus oil, including lemon, orange, grape, lime and grapefruit, and fruit essences, including apple, pear, peach, strawberry, raspberry, cherry, plum, pineapple, apricot, and so on. Flavors that have been found to be particularly useful include the commercially available flavors of orange, grape, cherry and chewing gum, and mixtures thereof. The amount of flavoring may depend on numerous factors, including the desired organoleptic effect. The flavors may be present in an amount within the range of about 0.5% to about 3.0% by weight of the composition. The commonly accepted flavors include grape and cherry flavors, and citrus flavors such as orange. It is also appreciated that the inclusion of the flavoring agents may also influence the final taste of the vehicle, making it more suitable for the ingestion of the drug. According to another aspect of the invention, a bioadhesive, such as a bioadhesive polymer, generally increases the contact time between the composition and the oral mucosa; particularly when the composition is administered directly in the oral cavity and the dissolution medium is saliva with mucoadhesive properties, the compositions of the invention are particularly useful for difficult patients. Specifically, pediatric patients, non-cooperative patients and / or rebellious patients are prevented or have difficulty spitting composition. This provides more accurate dosing and compliance with a desired dosage regimen. Non-limiting examples of known bioadhesives or mucohadenives include carbopol (various grades), carboxy methylcellulose sodium, methylcellulose, polycarbophil (Noveon AA-1), hydroxypropylmethylcellulose, hydroxypropyl cellulose, sodium alginate and sodium hyaluronate. In another aspect, one or more effervescent disintegrating agents may be used. Effervescent disintegrating agents generally include at least one acid, such as citric acid, tartaric acid, malic acid, fumaric acid, adipic acid, succinic acid, acid anhydrides, acid salts and mixtures thereof, and at least one base or a carbonate source, such as alkali metal carbonate salts, bicarbonate salts, and mixtures thereof. The reaction of the acid and the base produces gas or causes effervescence in the oral cavity or in the liquid used to dissolve the composition before ingestion. With carbonate bases, dioxide gas is produced. The action of this agent can often help mask the objectionable flavors of active pharmaceutical ingredients, vitamins, minerals, and other medications. The positive organoleptic sensation that is achieved through the production of gas in the mouth, combined with the texture, the speed and the resulting effervescence sensation, also generally masks the undesirable flavors in the mouth. When effervescent agents are included, they can be included in the composition in several different ways. One method includes incorporating all of the effervescent agent into the fibrous matrix used to form the composition. Another way to incorporate an effervescent disintegrating agent is to include all the agent as an additive, which is mixed with the fibrous matrix after it is formed. Another method contemplates incorporating a portion of the disintegrating agent in the fibrous matrix and another portion of the disintegrating agent as an additive after the formation of the fibrous composition. The components of the composition, i.e., the collagen-based carrier and the medicament (s) and other desired excipients, when incorporated into the fiber, are processed or converted into stringy fibrous strands. The known technology used to form the main fibrous element of the composition is that of creating strands or making the active drug more fluid. For example, the components can be combined into strands or fluids in a mixed manner, where the carrier and the medicament, plus another excipient (s) would also require to be added so that any small or large portion of the finally formed fibrous matrix , or any individual portion of a cord or a fiber, would contain a proportion of the ingredients mentioned above in a desired ratio with respect to the ratio of all the ingredients of the composition. Those proportions will be formed as desired for the purpose of dose measurement and to ensure reproducible dosing of the medicament for a patient. Conventional known methods of fiber and strand formation can be employed, including extrusion, coextrusion, gel casting, flash drying and freeze drying techniques. Many collagen materials are commercially available, or can be extracted following well-known biochemical practices. A suitable method for extraction and reconstitution from a source is described in US Patent No. 6,197,934, the disclosure of which is incorporated herein by reference in its entirety. Generally, collagen is extracted by acid, extracted by salt, or solubilized chemically and enzymatically and extracted in a state of small or molecular aggregate, from the source of raw material. These extracts are typically stabilized in a warm acid solution and kept refrigerated for a longer shelf life. Reconstitution causes the collagen molecules or aggregates to self-assemble into a fibrous structure that is often similar to their original native state. The reconstitution (or self-assembly) procedure can be induced by titrating the collagen solution to conditions that approximate its physiological state (pH 7.0-7.4 and 20-35 ° C in an ionically balanced phosphate buffer). Alternatively, the collagen can be precipitated by rapidly increasing the pH above 7.4 and removing the water from the solution, thereby increasing the concentration of solids. Before, during or after reconstitution or precipitation, a desired and compatible drug, such as an API, is added to the collagen. Then the collagen can be subjected to a compression procedure where the reconstituted collagen (CR) -medication is squeezed in one or more layers, draining the liquid from the solution to result in a solid material that dries quickly. This solid is collected and molded into a desired shape before drying. In the case where the CR and the drug are incompatible in the solid form, the layered assembly procedure is performed sequentially with independent CR gels, preformed, semi-dried or dried collagen matrices, and drug solutions, to form alternating layers of CR and medication. With reference to Figures 3A-3F, there is shown an exemplary method for making a composition 30 of the present invention. As shown, a viscous solution of reconstituted collagen (CR) 40 is first emptied into a draining surface 42 of the appropriate collection equipment and the compression or squeezing member 46 is pushed, or otherwise moved through the CR 10, squeezing or compressing the CR 10 into a thin layer 44 while forcing the outlet of the largest portion of the CR 10 liquid through the drain 48. The surface 42 may be sufficiently designed and configured to drain the liquid into the drain 48. As illustrated in Figure 3B, a thin layer 44 may require the member 46 to remove the excess CR 47. Next, a quantity of a drug composition or solution 50 (eg, API) is poured over a layer 44, to form a second layer. The emptying surface 42 is lowered vertically with the layer 44 to provide a volume that captures the medicament 50 to form the second layer (see Figure 3C). Then, the second layer 52 is also compressed or squeezed with the member 46 to force the liquid of the medicament solution 50 through the drain 48, thereby forming the second layer 52 of a medicament on the first layer 44 of CR. Again, as shown in Figure 3D, the additional material 53 could be removed. Another CR layer 54 is formed in a similar manner, to sandwich the drug layer 52 between the layers 44 and 54, as shown in the Figures. 3E and 3F. Figure 4 illustrates a schematic view of the composition 60 formed through the method shown in Figures 3A-3F. Figure 5 illustrates the final composition of the product formed with the multiple layers together. Another suitable method for preparing the fibrous composition according to the present invention is a printing process. With reference to Figure 6, there is shown an exemplary method of printing successive layers of CR followed by a medicament in a desired amount. As shown, a CR layer 70 can be printed with a protein printer head 72 and after the CR layer has dried, a drug layer 74 can be printed on the CR layer 70. Therefore, sequential layers 70 of CR, or specific areas of the CR 70 layer (s), can be printed with the medicament material, to form an interleaved type composition 76, as illustrated in Figure 7. , which comprises two layers of CR interspersed with the drug layer. This printing method allows uniformly distributing and / or controlling the amount of the drug on the CR layer 70. The printing process described in Figure 6 can be used and controlled selectively to vary the distribution and / or amount of medication in the product 76. For example, a larger amount of medication could be deposited at a site of the invention. layer 70, such as in the center, then in another site, such as the periphery. In addition, different APIs could be used in different areas of the product 76. For example, an API could be placed in a section, a quadrant or a half of the product, while another API could be deposited in a different section, quadrant or half of the product. The final composition 76, as shown in Figure 7, can then be perforated, scored and / or marked, such as with lines 80, to indicate the dosage, quantities and / or other desired information. Yet another suitable method for forming the fibers or ropes is the extrusion process, such as electrostatic extrusion. Generally the extrusion can be performed without rotating and / or melting any of the extruded components. Two or more extruded streams of some or all of the components of the composition can be made to converge and be mixed to form the cords or fibers used in the composition. The extruded fibers or filaments can then be formed on a reel or processed in many other ways. For example, the fibers can be aligned in sheets. The sheets can be stacked in layers one on top of the other. For example, each fiber in a sheet or layer can be oriented in one direction, ie, horizontally or from top to bottom, while the fibers in another sheet can be oriented with a vertical nature, or generally perpendicular with respect to the orientation of the fibers in the adjacent sheet (s). The stacking of the layers may involve the alternation of the horizontally or vertically oriented sheets or instead the all successive sheets may be with the fibers oriented horizontally or with all the fibers oriented vertically. Other combinations are also contemplated here, such as forming fiber layers or cross hatched and crosshatched strands, as will be appreciated by those skilled in the art. By virtue of being fibrous, the composition can then be compressed into unique desirable forms. For example, the sheets can be compressed into multi-layer "sheets", and then molded into the desired shapes, including, without limitation, a biconvex shape, a biconcave shape, a flattened shape, and the like. The particular orientation of the layers will generally affect the tensile strength and / or the ability of the layers or the sheet of layers to absorb liquid.

With reference to Figure 1, there is shown a top-to-bottom view of a final example form of the fibrous composition. As shown, the composition 10 has a circular shape. The composition 10 includes a central area 14 and terminal or peripheral areas 16, 18. The central area 14 generally contains a concentration of fibers with collagen base and medicament in a desired weight ratio. The composition 10 can also be perforated and / or marked as desired. For example, notch lines 21 divide the composition into 10 quadrants. With reference to Figure 2, there is shown a side view of the example form of the composition shown in Figure 1. As shown, the central area 14 is raised or raised with reference to the peripheral or terminal areas. 16, 18. The terminal areas 16, 18 are more compressed and flattened. In that sense, the composition takes a fusiform form. Once the desired forms have been formed, the composition could then be processed using the kiss cut technology to perforate or separate the desired amounts of the composition for the purposes of titration of the dose and administration of the dose. The notched design of the composition makes it easier to tear or cut the composition precisely. Accordingly, a single dose can be obtained more easily and conveniently, by simply cutting or fragmenting the notched sections of the composition. Alternatively, the layers, sheets or sheets of the fibrous composition can be made commercially available and subsequently processed to contain or "wrap" a pill or tablet. The fibrous composition or matrix can be configured with an API that is released immediately upon ingestion of the composition. Wrapped in it, there may be a pill, a tablet or another form of dose that is then ingested to release its API in a more delayed manner in the intestine. The APIs between the fibrous composition and the other dosage forms (eg, pill / tablet) can be the same or different. In addition, multiple API's can be incorporated in each dosage form. Each sheet and / or fiber sheet can be "marked" to indicate the nature and / or the amount of medication, the dosing regimen, day indications, time indications, and the like, as desired. The markings can also indicate the content of each notched section of the composition. The ability to mark the composition provides the advantage of allowing the manufacturer to comply with FDA regulations and other identification requirements. The composition can be marked with the colors of medicine approved by the FD &C or with other GRAS elements in halves, quarters or other dose sizes. The markings in the rooms are generally adequate for solid oral medications. The present invention will be better appreciated in light of the following example.

The following is an example of a fibrous, collagen-based medicament containing a composition of the present invention prepared by a gel-casting method. The collagen in a 3 mg / ml acidic aqueous solution is cold dialyzed against a 32.7 mM phosphate buffer at a pH range of about 7.0 to 7.4. This solution is emptied into molds and the temperature is increased to about 20 ° C-35 ° C. After a period of time, typically about several minutes, the solution changes to turbidity when the collagen begins to undergo molecular self-assembly. This procedure is called fribrilogenesis, or reconstitution, and is completed when all the collagen-free molecules have been added to each other. The resulting aggregate is a gel matrix with high water content, containing collagen fibrils, produced through a process that is generally known as thermal gelation. The structure of the fibril is normally formed with a non-hatched random pattern, but can be influenced by convection, shear flow or electromagnetic fields to generate oriented structures having unique properties, as described in US Patent No. 4,544,516, the disclosure of which is incorporated herein by reference in its entirety. The selected medicaments, such as an API, can be added to the collagen solution before gelation, or they can be dialyzed or otherwise infiltrated in the aqueous gels formed by known methods, before gel drying. The drained gels are then dried generally through freeze drying or air drying. The frozen drying provides a porous matrix with a collagen base with a large surface area, suitable for the oral drug delivery system of the present invention. The portions of a frozen dried cast film or the individual molded sections can be compressed, laminated or otherwise mechanically modified to form the desired forms for administration to a patient. The medicament may be added before or after the gel is formed to provide the final form of the composition administered in the oral drug delivery system of the invention. Forming or rolling can be facilitated by rewetting the dried matrix or adding liquid collagen to the matrix and drying it again while casting the matrix in the desired shape. By virtue of the foregoing, the present invention provides a system for supplying medicament for orally administering a medicament to a patient. The invention takes advantage of the desirable properties of the collagen protein, which has previously been used in a variety of useful medical applications, while also considering the weaknesses of traditional oral delivery methods. More specifically, the invention provides a composition constructed from a collagen or collagen-based fiber matrix carrying one or more drugs, and assembled in such a way that it disperses or dissolves when presented to the oral mucosal membrane of the oral cavity As such, the invention solves the difficulties with traditional methods of oral administration, such as those involving swallowing a pill, tablet, capsule or other solid dosage form. The fibrous, collagen-based composition is flexible, easily soluble in the oral environment, and can be further made appetizing with sweeteners, form, colors, flavor improvers, taste maskers, and the like, to make it more attractive for ingestion both for children as for adults. The titration of the dose of the composition is possible due to its physical structure and its characteristics. Specifically, the doses can be titrated by administering segmented portions of the fibrous matrix composition, simply by cutting it with scissors or a knife. In addition, the addition of a liquid medication in low doses over and within the composition, can create a medication that is swallowed in an individual unit. Particularly, the forms of the composition having larger centers that are less compacted, generally contain more space or air between the individual fibers or filaments, thereby allowing the absorption of the liquid. In that sense, the composition acts as a sponge to absorb and contain the liquid medication. The liquid could include the same API as an API built into the fibrous matrix. Alternatively, this may be different. Even more, liquid medication could be the only API in the entire product.

Another advantage is that the composition, by virtue of its flexible fibrous matrices, has the ability to "wrap" another dry medication, such as a pill or a powder, to create an individual unit of medicine to swallow. The molding of the composition into the desirable forms, as well as the fact that it has self-adhering properties by virtue of the other excipients desired therein along the edges of the composition, also allow the composition of a single unit of medication for swallow Therefore, the present invention improves the ingestion of a dose of medicament and, therefore, improves the patient's cooperation for ingestion in accordance with a medication regimen. Although the present invention has been illustrated through the description of the modalities thereof, and although the embodiments have been described in considerable detail, it is not intended to restrict or limit in any way to that detail the competence of the claims. For those skilled in the art, further advantages and modifications will readily become apparent. Therefore the invention, in its broader aspects, is not limited to the specific details, representative apparatuses, methods and examples described. Accordingly, derivations can be made from the details without departing from the competence and spirit of the general concept of the Applicant's invention.

Claims (30)

NOVELTY OF THE INVENTION CLAIMS

1. An oral composition for drug delivery comprising a flexible matrix, the matrix formed by a plurality of fibers comprising a collagen-based carrier and a medicament, the composition being orally soluble to deliver a dosage unit of the medicament.

2. The composition according to claim 1, further characterized in that the collagen-based carrier comprises chemically modified collagen.

3. The composition according to claim 1, further characterized in that the ratio by weight of carrier to medicament in each fiber is in the range of about 1: 50 to about 50: 1.

4. The composition according to claim 1, further characterized in that the weight ratio of carrier to medicament in each fiber is in the range of about 1: 1.

5. The composition according to claim 1, further characterized in that it has multiple layers of fibers.

6. The composition according to claim 1, further characterized in that it is compressed into one of a biconvex shape, a biconcave shape, a flattened shape and a fusiform shape.

The composition according to claim 1, further characterized in that it includes individual sections, each section comprising a dosage unit of the medicament.

The composition according to claim 1, further characterized in that the medicament is an agent selected from: an opioid analgesic agent, a non-opioid analgesic agent, an anti-inflammatory agent, an antitussive agent, an antipyretic agent, an antibiotic agent, an antimicrobial agent, a steroidal agent, an amphetamine stimulating agent, a non-amphetamine stimulating agent, a laxative agent, an anorectic agent, an antihistamine agent, an antiasthmatic agent, an antidiuretic agent, an antiflazing agent, an anti-migraine agent, an antispasmodic agent, an anti-diabetic agent, a respiratory agent, a sympathomimetic agent, an H2-blocking agent, an antihyperlipidemic agent, an anti-cholesterol agent, a cardiotonic agent, a vasodilating agent, a vasoconstrictor agent, a sedative agent, a hypnotic agent, a anticonvulsant agent, a muscle relaxant agent, an antipsychotic agent, an age anti-anti-anxiety agent, an anti-hyperactive agent, an antihypertensive agent, an antitumor agent, a soporific agent, a tranquilizer, a decongestant, a beta-blocker, a non-spheroid hormone, an herbal agent, an enzyme, a humoral agent, a madrhagic agent, a psychic energizer, a vitamin, a mineral, a dietary supplement, and combinations thereof.

The composition according to claim 1, further characterized in that the medicament is present in an amount within the range of about 1 mg to about 100 mg.

The composition according to claim 1, further characterized in that it further comprises an excipient selected from the group consisting of: a sugar, a binding agent, non-effervescent disintegrants, a coloring agent, a flavoring agent, a masking agent of flavor, an oral dispersing agent, a stabilizer, a preservative, a diluent, a filler, a compaction agent, an effervescent disintegrating agent and combinations thereof.

The composition according to claim 1, further characterized in that it further comprises a mucoadhesive in an amount sufficient to adhere the composition to the buccal membrane of a patient.

12. The composition according to claim 1, further characterized in that the medicament is incorporated within each fiber in the matrix.

13. The composition according to claim 1, further characterized in that the medicament is distributed over the flexible matrix.

14. The composition according to claim 1, further characterized in that it comprises drug layers interspersed between layers of the flexible matrix.

15. The composition according to claim 1, further characterized in that it further comprises a second dosage formulation independent of the flexible matrix.

16. An oral drug delivery system comprising the composition defined in claim 1.

17. An oral drug delivery system comprising a pharmaceutical composition including: at least one layer formed of a plurality of fibers with base of collagen; and a medicament, the composition being soluble to deliver a dosage unit of the medicament to the patient's oral cavity.

18. The delivery system according to claim 16, further characterized in that the composition includes a drug layer between two layers of collagen-based fibers.

19. The composition according to claim 16, further characterized in that the ratio by weight of fiber to medicament is in the range of about 1: 50 to about 50: 1.

The composition according to claim 16, further characterized in that the ratio by weight of fiber to medicament is in the range of about 1: 1.

21. The composition according to claim 16, further characterized in that the medicament is an agent chosen from: an opioid analgesic agent, a non-opioid analgesic agent, an anti-inflammatory agent, an antitussive agent, an antipyretic agent, an antibiotic agent, an agent antimicrobial, a spheroidal agent, an amphetamine-stimulating agent, a non-amphetamine-stimulating agent, a laxative agent, an anorectic agent, an antihistamine agent, an antiasthmatic agent, an antidiuretic agent, an antiflazing agent, an antimigraine agent, an antispasmodic agent , an antidiabetic agent, a respiratory agent, a sympathomimetic agent, an H2-blocking agent, an antihyperlipidemic agent, an anti-cholesterol agent, a cardiotonic agent, a vasodilating agent, a vasoconstrictor agent, a sedative agent, a hypnotic agent, an anticonvulsant agent , a muscle relaxant agent, an antipsychotic agent, an anti-inflammatory agent Anxiolytic, an antihypertensive agent, an antihypertensive agent, an antitumor agent, a soporific agent, a tranquilizer, a decongestant, a beta blocker, a non-spheroid hormone, an herbal agent, an enzyme, a humoral agent, a madrhagic agent, an energizer psychic, a vitamin, a mineral, a dietary supplement, and combinations thereof.

22. The composition according to claim 16, further characterized in that the fibers comprise chemically modified collagen.

23. The use of a flexible matrix formed of a plurality of fibers comprising a collagen-based carrier and a medicament, for the preparation of an orally soluble dosage unit for orally delivering a medicament to a patient.

24. The use claimed in claim 23, further comprising combining the composition with an aqueous-based liquid before administering the composition to the patient.

25. The use claimed in claim 23, wherein a second pharmaceutical formulation in combination with the composition is also administrable.

26. The use claimed in claim 25, wherein the second pharmaceutical composition is administrable simultaneously or sequentially with the composition.

27. The use claimed in claim 23, wherein the patient is one of a child and an adult.

28. A method for formulating an orally soluble medicament composition, the method comprising: forming multiple fibers from a collagen-based material; and combining a medicament with the fibers to formulate the orally soluble medicament composition.

29. The method according to claim 28, further characterized in that it further comprises providing reconstituted collagen to form the multiple fibers.

30. The method according to claim 28, further characterized in that it further comprises compressing the multiple fiber layers with the medicament, to form the orally soluble medicament composition.