HK1141740A - Dual portion lozenge dosage form - Google Patents

Description

Two-part lozenge dosage form

Technical Field

The present invention relates to dosage forms comprising both a disintegrating tablet portion and a hard candy portion and uses thereof.

Background

Medicaments intended for oral administration are usually provided in solid form, such as tablets, capsules, pills, lozenges or granules. Rapidly disintegrating tablets are often employed in drug administration where it is impractical to provide an integral swallowed tablet (e.g., for pediatric patients). There are several researchers in the field exploring ultrafast disintegrating tablets (e.g., U.S. Pat. Nos. 6,106,861 and 6,024,981 and PCT patent application No. WO 99/47126).

Applicants' invention relates to a two-part dosage form that combines the use of a rapidly disintegrating tablet comprising a pharmaceutically active agent with a relatively slow disintegrating hard candy part (e.g., a lozenge). Thus, the dosage form provides both the benefits of rapid delivery of the pharmaceutically active agent contained in the rapidly disintegrating tablet portion and slower degradation of the hard candy portion, which may contain a second pharmaceutically active agent.

Disclosure of Invention

The present invention relates to a dosage form comprising both a disintegrating tablet portion and a hard candy portion, wherein: (i) the disintegrating tablet portion comprises at least one pharmaceutically active agent, and (ii) the hard candy portion covers at least 20% of the surface of the disintegrating tablet portion, and wherein the disintegration time of the hard candy portion is at least five times (e.g., at least ten times) the disintegration time of the disintegrating tablet portion. Other features and advantages of the invention will be apparent from the description of the invention and from the claims.

Detailed Description

It is believed that one skilled in the art can, using the description herein, utilize the present invention to its fullest extent. The following specific embodiments are to be construed as merely illustrative, and not limitative of the remainder of the disclosure in any way whatsoever.

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. In addition, all publications, patent applications, patents, and other references mentioned herein are incorporated by reference. As used herein, all percentages are by weight unless otherwise indicated.

Disintegrating tablet portion

The dosage form of the present invention includes a disintegrating tablet portion. The disintegrating tablet portion comprises one or more pharmaceutically active agents, and optionally one or more compressible excipients, water-swellable excipients, effervescent couple, and other ingredients.

In one embodiment, the hardness of the disintegrating tablet portion is less than about 15kp/cm²E.g. less than 10kp/cm²E.g. less than 5kp/cm². In one embodiment, a sufficient amount of energy is applied to the disintegrating tablet portions for a sufficient period of time to reduce their hardness. In one embodiment, the disintegrating sheet portions are energized in the form of heat or electromagnetic radiation (e.g., microwaves). Depending on the composition of the disintegrating tablet portions, in one embodiment, heating may be generally in the range of ambient temperature to 100 ℃ or higher for a time sufficient to achieve a softening effect.

In one embodiment, the friability of the disintegrating tablet portion is less than about 2% (e.g., less than about 1%, e.g., less than about 0.5%) prior to applying energy to the disintegrating tablet portion, which is the second step of the method. Page 1981 of USP 23(1995)1216 discusses the friability of the disintegrated tablet portion.

In one embodiment, the disintegrating tablet portion is designed to dissolve in the oral cavity in less than about 60 seconds (e.g., less than about 45 seconds, such as less than about 30 seconds, such as less than about 15 seconds) when placed on the tongue.

Compressible excipient

In one embodiment, the disintegrating tablet portion comprises one or more compressible excipients. By compressible excipient is meant an ingredient that can be compressed into a tablet without the addition of other binders. In one embodiment, the compressible excipient is in the form of a hydrate and may be selected from organic compounds such as dextrose monohydrate, maltodextrin, lactose monohydrate, and dextrin; and inorganic compounds including dibasic calcium phosphate dihydrate, dibasic sodium phosphate heptahydrate, dibasic sodium phosphate dodecahydrate, monobasic sodium phosphate monohydrate, and monobasic sodium phosphate dihydrate. In one embodiment, the disintegrating tablet portion comprises a compressible excipient selected from the group consisting of isomalt, dextrose monohydrate, maltodextrin, lactose monohydrate, dextrin, mannitol, lactitol, sorbitol, xylitol, erythritol, sucrose, and lactose.

In one embodiment, the compressible excipient is in the form of granules having an average particle size of about 50 to about 500 microns, such as about 75 to about 400 microns.

In one embodiment, the disintegrating tablet portion comprises from about 5% to about 90% by weight, such as from about 15% to about 75% by weight, of one or more compressible excipients. In one embodiment, the disintegrating tablet portion comprises at least 40 wt% of one or more compressible excipients, based on the total weight of the disintegrating tablet portion.

Water swellable excipient

In one embodiment, the disintegrating tablet portion further comprises one or more water-swellable excipients. A water-swellable excipient refers to a material designed to swell or wick liquid when in contact with a liquid medium and to aid disintegration of the compressed tablet. The water-swellable excipient may be selected from superdisintegrants (e.g., cross-linked polyvinylpyrrolidone, cross-linked carboxymethylcellulose, sodium carboxymethyl starch), cellulosic compounds (e.g., microcrystalline cellulose, starch, alginic acid), and inorganic clays (e.g., bentonite, attapulgite, and magnesium aluminum silicate). In one embodiment, the water-swellable excipient is at least partially hydrated and is selected from the group consisting of sodium carboxymethyl starch, cross-linked polyvinylpyrrolidone, cross-linked carboxymethyl cellulose, microcrystalline cellulose, starch, hydroxypropyl cellulose, and alginic acid.

In one embodiment, the amount of water-swellable excipient in the disintegrating tablet portion is from about 0.1% to about 5% by weight, for example from about 0.5% to about 3% by weight, of the total weight of the disintegrating tablet portion.

In one embodiment, the amount of compressible excipient is greater than the amount of water swellable excipient. In one embodiment, the ratio of compressible excipient to water swellable excipient in the disintegrating tablet portion is from about 1: 1 to about 150: 1, such as from about 10: 1 to about 100: 1, for example from about 25: 1 to about 75: 1.

Effervescent couple

In one embodiment, the disintegrating tablet portion further comprises one or more effervescent couples. In one embodiment, the effervescent couple comprises an ingredient selected from the group consisting of sodium bicarbonate, potassium bicarbonate, calcium carbonate, magnesium carbonate, sodium carbonate and an ingredient selected from the group consisting of citric acid, malic acid, fumaric acid, tartaric acid, phosphoric acid, alginic acid.

In one embodiment, the total amount of effervescent couple in the disintegrating tablet portion is from about 0.1 wt% to about 20 wt%, for example from about 2 wt% to about 10 wt%, of the total weight of the disintegrating tablet portion.

Other ingredients

The disintegrating tablet portion may contain other conventional ingredients, including other fillers, including water-soluble compressible carbohydrates such as dextrose, sucrose, mannitol, sorbitol, maltitol, xylitol, lactose, and mixtures thereof; other conventional dry binders such as polyvinylpyrrolidone and the like; sweeteners such as aspartame, acesulfame potassium, sucralose and saccharin; lubricants, such as magnesium stearate, stearic acid, talc and waxes; a preservative; a flavoring agent; a disintegrant; an antioxidant; acidulants such as, but not limited to, citric, malic, tartaric, ascorbic and fumaric acids; a surfactant; and a colorant.

Preparation of

The disintegrating tablet portion can be prepared by a variety of tableting methods. Conventional methods for tablet production include direct compression ("dry blending"), tableting after dry granulation and drying and tableting after wet granulation. Other methods include the use of compaction roller techniques such as chilsonator or drop rollers, or molding, casting or extrusion techniques. All these methods are well known in The art and a detailed description can be found, for example, in Lachman et al, "The Theory and Practice of Industrial Pharmacy", Chapter 11, 3 rd edition, 1986.

In one embodiment, the disintegrating tablet portion is formed by a direct compression process that involves direct compression of a blend of the pharmaceutically active agent, the compressible excipient, the water-swellable excipient, and any other suitable optional ingredients. After blending, a predetermined volume of the granules is filled into the die cavity of a rotary tablet press, which is continuously rotated as part of a "die plate" from a filling station to a tablet press station. The granules are compacted between an upper punch and a lower punch and then fed to a tablet discharge station where, upon reaching this position, the lower punch pushes the resulting disintegrated tablet portion out of the die cavity and then a fixed "stripper" bar directs it to a tablet discharge chute.

Multiple layers

In one embodiment, the disintegrating tablet portion has multiple layers comprising at least one different component. In one embodiment, the tablet portion comprises two layers, wherein a first layer comprises a pharmaceutically active agent and a second layer comprises a second pharmaceutically active agent different from the pharmaceutically active agent contained within the first layer. In one embodiment, the disintegrating tablet portion comprises two layers, wherein both the first and second layers comprise the same pharmaceutically active agent, and wherein the pharmaceutically active agent in the second layer is coated with a modified release coating, or is in the form of a matrix that dissolves in a modified release manner. In one embodiment, the second layer comprises particles of the active ingredient substantially coated with a modified release coating. As used herein, the term "substantially covers" means that the coating typically covers the entire surface (e.g., the surface of the active ingredient, core, or underlying layer) so that little or no active ingredient, core, or underlying layer is exposed. As used herein, "substantially coated" means that less than about 20%, such as less than about 15%, or less than about 1.0% of the surface is exposed, e.g., not covered with a desired coating.

In one embodiment, both the first layer and the second layer are exposed to a surface of the dosage form.

In one embodiment, one layer of the bi-layer disintegrating tablet portion comprises one flavor, while a second layer comprises a different secondary flavor, in order to produce a taste profile in sequence.

In one embodiment, the first layer of the double layer disintegrating tablet portion comprises one immediate release active ingredient, while the second layer comprises the same or a different active ingredient than the first active ingredient, and the active ingredient is delivered in a modified release manner.

In one embodiment, a rounded compressed bilayer disintegrating tablet is partially surrounded by a lozenge, with the surface of the first layer of the disintegrating tablet exposed at the top of the dosage form and the surface of the second layer of the disintegrating tablet exposed at the bottom of the dosage form.

Hard candy part

The dosage form of the present invention includes a hard candy portion. In one embodiment, the hard candy portion is a sugar glass hard candy formed by cooling boiled candy. In another embodiment, the hard candy portion is a pressed ice confection prepared by compaction having a hardness of at least 15 kilograms, such as at least 20 kilograms.

In one embodiment, the hard candy portion comprises one or more sugars selected from the group consisting of: isomalt, sucrose, lactose, dextrose, corn syrup, lactitol, and maltitol (lycasin). In one embodiment, the hard candy portion comprises at least 50 wt.% (e.g., at least 75 wt.%, such as at least 90 wt.%) of such sugars. In one embodiment, the hard candy portion is substantially free of sucrose (e.g., the sugar portion contains isomalt or lactose).

In one embodiment, a hard candyThe hardness of the part is more than about 15kp/cm²。

In one embodiment, the hard candy portion comprises a pharmaceutically active agent. In one embodiment, the hard candy portion comprises a pharmaceutically active agent that is different from the pharmaceutically active agent contained within the disintegrating tablet portion.

The sugar glass hard candy portion may be made by a variety of methods including, but not limited to uniplast rolling, rolling and subsequent cutting and stamping, and deposition in a mold. These molds may be made of metal, rubber, resin, or plastic.

Compressed lozenges are prepared by tableting and compression techniques known in the art of tablet preparation, but the compressed hardness of the lozenge is higher than the traditional compressed hardness of a chewable, disintegrating or swallowable tablet, i.e. higher than 15 kgf, and are designed to dissolve slowly in the mouth.

Pharmaceutically active agents

The dosage form of the present invention comprises at least one pharmaceutically active agent. By "pharmaceutically active agent" is meant a formulation (e.g., a compound) that is approved or approved by the U.S. food and Drug Administration, the European Medicines Agency, or any subsequent entity thereof, for oral treatment of a condition or disease. Suitable pharmaceutically active agents include, but are not limited to, analgesics, anti-inflammatory agents, antihistamines, antibiotics (such as antibacterial, antiviral, and antifungal agents), antidepressants, antidiabetic agents, spasmolytics, appetite suppressants, bronchodilators, cardiovascular therapeutics (such as statins), central nervous system therapeutics, antitussives, decongestants, diuretics, expectorants, gastrointestinal therapeutics, anesthetics, mucolytics, muscle relaxants, osteoporosis therapeutics, stimulants, nicotine, and sedatives.

Examples of suitable gastrointestinal therapeutic agents include (but are not limited to): antacids such as aluminum-containing active ingredients (e.g., aluminum carbonate, aluminum hydroxide, dihydroxyaluminum sodium carbonate, and aluminum phosphate), bicarbonate-containing active ingredients, bismuth-containing active ingredients (e.g., bismuth aluminate, bismuth carbonate, bismuth subcarbonate, bismuth subgallate, and bismuth subnitrate), calcium-containing active ingredients (e.g., calcium carbonate), glycine, magnesium-containing active ingredients (e.g., magnesium aluminum hydroxide, magnesium aluminosilicate, magnesium carbonate, magnesium glycinate, magnesium hydroxide, magnesium oxide, and magnesium trisilicate), phosphate-containing active ingredients (e.g., aluminum phosphate and calcium phosphate), potassium-containing active ingredients (e.g., potassium bicarbonate), sodium-containing active ingredients (e.g., sodium bicarbonate), and silicates; laxatives, such as laxatives (e.g., docusate) and stimulant laxatives (e.g., bisacodyl); h2 receptor antagonists such as famotidine, ranitidine, cimetidine, and nizatidine; proton pump inhibitors such as omeprazole and lansoprazole; gastrointestinal cytoprotective agents such as sucralfate and misoprostol; gastrointestinal prokinetic agents, such as prucalopride; antibiotics against helicobacter pylori, such as clarithromycin, amoxicillin, tetracycline, and metronidazole; antidiarrheals, such as bismuth subsalicylate, kaolin, diphenoxylate, and loperamide; glycopyrrolate; analgesics, such as aminosalicylic acid; antiemetics, such as ondansetron, benoxazine, diphenhydramine, dimenhydrinate, meclizine, promimedium, and hydroxyzine; probiotics, including but not limited to lactobacillus; lactase; racecadotril; and air expulsion agents such as polydimethylsiloxanes (e.g., dimethylsiloxanes and simethicone, including those described in U.S. Pat. Nos. 4,906,478, 5,275,822, and 6,103,260); their isomers; and pharmaceutically acceptable salts and prodrugs (e.g., esters) thereof.

Examples of suitable analgesics, anti-inflammatory agents and antipyretics include, but are not limited to, non-steroidal anti-inflammatory drugs (NSAIDs), such as propionic acid derivatives (e.g., ibuprofen, naproxen, ketoprofen, flurbiprofen, fenbufen, fenoprofen, indoprofen, fluprofen, pirprofen, carprofen, oxaprozin, pranoprofen, and suprofen) and COX inhibitors, such as celecoxib; acetaminophen; acetylsalicylic acid; acetic acid derivatives such as indomethacin, diclofenac, sulindac, and tolmetin; fenamic acid derivatives, such as mefenamic acid, meclofenamic acid, and flufenamic acid; bibenzoic acid derivatives such as diflunisal and fluoroacetylsalicylic acid; and oxicams, such as piroxicam, sudoxicam, isoxicam and meloxicam; their isomers; and pharmaceutically acceptable salts and prodrugs thereof.

Examples of antihistamines and decongestants include, but are not limited to, brompheniramine, clorazine, dexbrompheniramine, bromhexine, phenindamine, pheniramine, mepyramine, pinzirazine, pripolidine, ephedrine, phenylephrine, pseudoephedrine, norephedrine, chlorpheniramine, dextromethorphan, diphenhydramine, doxylamine, astemizole, terfenadine, fexofenadine, naphazoline, oxymetazoline, montelukast, propylhexedrine, phenylpropridine, clindamycin, acrivastine, pruimedine, oxolamine, mequitazine, amphetamine, bromhexine, ketotifen, terfenadine, ebastine, phenizine, xylometazoline, loratadine, desloratadine, and cetirizine; their isomers; and their pharmaceutically acceptable salts and esters.

Examples of antitussives and expectorants include, but are not limited to, diphenhydramine, dextromethorphan, noscapine, chlophedianol, menthol, benzonatate, ethylmorpholine, codeine, acetylcysteine, carbocysteine, ambroxol, belladonna alkaloids, sobutyrol, guaiacol, ambroxol, and guaifenesin; their isomers; and pharmaceutically acceptable salts and prodrugs thereof.

Examples of muscle relaxants include, but are not limited to, cyclobenzaprine and chlorzoxazone, metaxalone, oxyphennara, methocarbamol; their isomers; and pharmaceutically acceptable salts and prodrugs thereof.

Examples of stimulants include, but are not limited to, caffeine.

Examples of sedatives include, but are not limited to, hypnotics, such as antihistamines (e.g., diphenhydramine), eszopiclone, and zopiclone; their isomers; and pharmaceutically acceptable salts and prodrugs thereof.

Examples of appetite suppressants include, but are not limited to, norephedrine, phentermine, and diethylpropion; their isomers; and pharmaceutically acceptable salts and prodrugs thereof.

Examples of anesthetics (e.g., for the treatment of sore throat) include, but are not limited to, dyclonine, benzocaine, and pectin; their isomers; and pharmaceutically acceptable salts and prodrugs thereof.

Examples of suitable statins include, but are not limited to, atorvastatin, rosuvastatin, fluvastatin, lovastatin, simvastatin, atorvastatin, pravastatin; their isomers; and pharmaceutically acceptable salts and prodrugs thereof.

In one embodiment, the pharmaceutically active agent contained in the disintegrating tablet portion is selected from the group consisting of phenylephrine, dextromethorphan, ambroxol, pseudoephedrine, acetaminophen, ibuprofen, ketoprofen, loperamide, famotidine, calcium carbonate, dimethicone, and menthol; their isomers; and pharmaceutically acceptable salts and prodrugs thereof.

In one embodiment, the pharmaceutically active agent comprised in the hard candy moiety is selected from phenylephrine, dextromethorphan, ambroxol, pseudoephedrine, chlorpheniramine, methocarbamol, clofedanol, ascorbic acid, menthol, pectin, dyclonine, and benzocaine; their isomers; and pharmaceutically acceptable salts and prodrugs thereof.

As mentioned above, the pharmaceutically active agents of the present invention may also be present in the form of pharmaceutically acceptable salts, such as acid/anion or base/cation salts. Pharmaceutically acceptable acid/anion salts include, but are not limited to, acetate, benzenesulfonate, benzoate, bicarbonate, bitartrate, bromide, calcium edetate, dexcamphorsulfonate, carbonate, chloride, citrate, dihydrochloride, edetate, edisylate, dedecyl propionate, ethanesulfonate, fumarate, glucoheptonate, gluconate, glutamate, p-hydroxyacetaminophenylarsonate, hexylresorcinate, hydrabamine, hydrobromide, hydrochloride, hydroxynaphthoate, iodide, isethionate, lactate, lactobionate, malate, maleate, mandelate, methanesulfonate, methylbromide, methylnitrate, methylsulfate, mucate, naphthalenesulfonate, nitrate, pamoate, pantothenate, phosphate/diphosphate, salts of citric acid, salts of lactic acid, salts of malic acid, salts of lactic acid, salts of, Polygalacturonate, salicylate, stearate, subacetate, succinate, sulfate, tannate, tartrate, theachlorate, tosylate, and triiodonium. Pharmaceutically acceptable basic/cationic salts include, but are not limited to, aluminum, benzathine, calcium, chloroprocaine, choline, diethanolamine, ethylenediamine, lithium, magnesium, meglumine, potassium, procaine, sodium, and zinc.

As mentioned above, the pharmaceutically active agents of the present invention may also exist in the form of prodrugs of the pharmaceutically active agent. Typically, such prodrugs will be functional derivatives of the pharmaceutically active agent which are readily convertible in vivo into the desired pharmaceutically active agent. The general procedures for selecting and preparing suitable prodrug derivatives are described, for example, in the following references: "Design of Prodrugs" (prodrug Design) ", edit: bundgaard, Elsevier, 1985. In addition to salts, the invention provides esters, amides, and other protected or derivatized forms of the compounds.

If the pharmaceutically active agents according to the invention have at least one chiral center, they may exist as enantiomers. If the pharmaceutically active agent has two or more chiral centers, they may also exist as non-enantiomers. It is to be understood that all such isomers and mixtures thereof are included within the scope of the present invention. In addition, certain crystal forms of the pharmaceutically active agent may exist as polymorphs and such polymorphs are intended to be included within the scope of the present invention. Moreover, certain pharmaceutically active agents may form solvates with water (e.g., hydrates) or common organic solvents, and such solvates are also intended to be included within the scope of the present invention.

In one embodiment, the pharmaceutically active agent is present in the dosage form in a therapeutically effective amount, which is an amount that produces the desired therapeutic response upon oral administration and is readily determined by one skilled in the art. In determining this amount, the pharmaceutically active agent to be administered, the bioavailability characteristics of the pharmaceutically active agent, the dosing regimen, the age and weight of the patient, and other factors must be considered, as is known in the art.

The pharmaceutically active agent may be present in various forms. For example, the pharmaceutically active agent within the dosage form may be dispersed (e.g., melted) at the molecular level or may be in the form of particles, which in turn may or may not have a coating. If the pharmaceutically active agent is in the form of particles, the particles (whether coated or uncoated) typically have an average particle size of about 1 to about 2000 microns (e.g., about 1 to about 1000 microns). In one embodiment, such particles are crystals having an average particle size of about 1 to about 300 microns. In another embodiment, the particles are granules or pellets having an average particle size of from about 50 to about 2000 microns, such as from about 50 to about 1000 microns, for example from about 100 to about 800 microns.

As is known in the art, if a pharmaceutically active agent is poorly tasting, the pharmaceutically active agent may be coated with a taste-masking coating. Examples of suitable taste-masking coatings are described in U.S. Pat. No.4,851,226, U.S. Pat. No.5,075,114, and U.S. Pat. No.5,489,436. Commercially available taste masked pharmaceutically active agents may also be used. For example, acetaminophen particles encapsulated with ethylcellulose or other polymers by a coacervation process can be used in the present invention. Coacervated encapsulated acetaminophen is commercially available from Eurand America, inc. (Vandalia, Ohio) or Circa Inc.

The pharmaceutically active agent may be present in pure crystalline form or in particulate form prior to the addition of a coating, such as a modified release or taste masking coating. Granulation techniques may be used to improve the flowability or particle size of the pharmaceutically active agent, making it more suitable for compression or subsequent coating. Suitable binders for granulation include, but are not limited to, starch, polyvinylpyrrolidone, polymethacrylates, hydroxypropylmethylcellulose, and hydroxypropylcellulose. The particles comprising the pharmaceutically active agent may be prepared by co-granulating the pharmaceutically active agent with suitable matrix particles using any granulation method known in the art. Examples of such granulation processes include, but are not limited to, high shear wet granulation and fluid bed granulation such as rotary fluid bed granulation, and details regarding these processes are disclosed in "The Theory and Practice of Industrial pharmacy", 3 rd edition, Chapter 11, Lachman, Leon et al, 1986.

In one embodiment, the pharmaceutically active agent is coated with a combination of a water insoluble film forming polymer such as, but not limited to, cellulose acetate or ethyl cellulose and a water soluble polymer such as, but not limited to, povidone, polymethacrylic acid copolymers such as those sold by Rohm America under the tradename Eudragit E-100, and hydroxypropylcellulose. In this embodiment, the ratio of water insoluble film forming polymer to water soluble polymer is from about 50% to about 95% water insoluble polymer and from about 5% to about 50% water soluble polymer, and the weight percent of the coating is from about 5% to about 40% by weight, based on the weight of the coated taste-masked particle.

In one embodiment, one or more active ingredients or a portion of a pharmaceutically active ingredient may be bound to an ion exchange resin in the disintegrating tablet portion or the lozenge portion to mask the taste of the pharmaceutically active ingredient or deliver the active ingredient in a modified release manner.

In one embodiment, the pharmaceutically active agent is capable of dissolving upon contact with a fluid, such as water, gastric acid, intestinal fluid, and the like. In one embodiment, the dissolution characteristics of the pharmaceutically active agent in the disintegrating tablet portion conform to the USP specifications for immediate release tablets containing the pharmaceutically active agent. For example, for acetaminophen tablets, USP 24 specifies that at least 80% of the acetaminophen contained in the dosage form is released from the dosage form within 30 minutes after administration using USP apparatus 2 (paddle) at 50rpm in phosphate buffer at pH 5.8, and for ibuprofen tablets, USP 24 specifies that at least 80% of the ibuprofen contained in the dosage form is released from the dosage form within 60 minutes after administration using USP apparatus 2 (paddle) at 50rpm in phosphate buffer at pH 7.2. See USP 24, 2000 edition, pages 19-20 and 856 (1999). In another embodiment, the dissolution characteristics of the pharmaceutically active agent are modulated: such as controlled release, sustained release, delayed release, retarded release, long acting, delayed release, etc.

Sialorrhea inducer

In one embodiment, the disintegrating tablet portion, the lozenge portion, or both, comprise one or more salivation inducing agents. Examples of suitable salivation inducing agents include, but are not limited to, muscarinic acetylcholine receptor agonists (e.g., pilocarpine and succulents, which are commercially available from IFF under the trade name SN 12011), sigma binders such as aralkylamines (e.g., N-disubstituted phenylalkylamines in which the alkyl group has from about 1 to about 8 carbons), N-disubstituted-2-phenylpropylamines, spirooxathiolane quinuclidines, heliotropium longipes (Heliopsis longipes) roots, and anticholinesterase agents. In one embodiment, the disintegrating tablet portion and/or the lozenge portion comprises a salivation inducing agent in an amount from about 0.1% to about 10% by weight of the disintegrating tablet portion.

Two-part dosage form

In one embodiment, the weight ratio between the disintegrating tablet portion and the hard candy portion is from about 10: 90 to about 60: 40. In one embodiment, the hard candy portion covers at least 20% of the surface area of the disintegrating tablet portion (e.g., covers at least 50% or at least 75% of the surface area, or covers substantially all of the surface of the disintegrating tablet portion). In one embodiment, the hard candy portion includes a plurality of openings that expose a surface area of the disintegrating tablet portion. In one embodiment, the hard candy portion covers substantially all of the surface of the disintegrating tablet portion, and wherein the hard candy portion further comprises a plurality of indentations adapted to dissolve and expose the surface of the disintegrating tablet portion upon contact with liquid in the oral cavity.

In one embodiment, the hard candy portion comprises a pharmaceutically active agent that is different from the pharmaceutically active agent contained within the disintegrating tablet portion.

In one embodiment, the dosage form of the present invention has a multi-layered structure in which the disintegrating tablet portion is one layer and the hard candy portion is another layer. In one embodiment, the surface of the first layer has a convex shape and the surface of the second layer has a concave shape. In another embodiment, the dosage form further comprises a third layer disposed between a surface of the first layer and a surface of the second layer, wherein the third layer comprises an edible binder-like material. In one embodiment, the edible binder-like material includes a component selected from the group consisting of polyethylene glycol, polyethylene oxide, polycaprolactone, carnauba wax, microcrystalline wax, opanols (opanols), shellac wax, and beeswax.

In one embodiment, the edible binder is pre-melted at between about 35 ℃ to about 100 ℃, added to one surface of the lozenge portion or one surface of the disintegrating tablet portion, and allowed to cool and harden at room temperature (e.g., about 25 ℃).

In another embodiment, the binder is added in powder form between the disintegrating tablet portion and the lozenge portion and heated in a separate step for at least 2 seconds between about 35 ℃ and about 120 ℃, then allowed to cool and harden at room temperature.

In another embodiment, the binder is applied by first preparing an aqueous solution of a sugar and/or polymer (such as, but not limited to, polymethacrylate, hydroxypropyl methylcellulose, hydroxypropyl cellulose, starch, and polyvinylpyrrolidone), then placing about 0.1mL to about 5mL of the solution (such as prepared at a solids content of about 1% to about 50%) on one surface of a lozenge, then adding a portion of the disintegrating tablet to the surface of the lozenge, and then drying the dosage form.

From about 0.05% to about 40%, for example from about 0.5% to about 10%, by weight of the total weight of the dosage form, of the edible binder may be added to the dosage form.

In one embodiment, the pharmaceutically active agent contained in the disintegrating tablet portion is selected from the group consisting of phenylephrine, dextromethorphan, ambroxol, pseudoephedrine, acetaminophen, ibuprofen, ketoprofen, loperamide, famotidine, calcium carbonate, dimethicone, menthol, and pharmaceutically acceptable salts or prodrugs thereof.

In one embodiment, the hard candy portion comprises a pharmaceutically active agent selected from the group consisting of phenylephrine, dextromethorphan, ambroxol, pseudoephedrine, chlorpheniramine, methocarbamol, clofedanol, ascorbic acid, menthol, pectin, dyclonine, benzocaine, and pharmaceutically acceptable salts or prodrugs thereof.

Disintegration test

The disintegration time of the hard candy portion of the dosage form is at least 10 times, such as at least 50 times or at least 100 times longer than the disintegration time of the disintegrating tablet portion. To determine the disintegration of the hard candy part and the disintegrating tablet part, a disintegration test against "uncoated tablets" according to USP30-NF25 (using water as immersion liquid) should be used. Briefly, one dosage unit was placed in each of the six tubes of the basket and water (maintained at 37 ± 2 ℃) was used as the dip. The disintegration time was measured by averaging ten measurements of the time required to completely disintegrate each tablet portion. In one embodiment, the disintegration time of the disintegrating tablet portion is less than about 30 seconds, for example less than about 15 seconds.

Hardness test

Hardness is a term used in the art to describe the radial rupture strength as measured by a Schleuniger hardness tester, as described by Leiberman et al in "Pharmaceutical Dosage Forms-Tablets", Vol.2, 2 nd edition, Marcel Dekker Inc., 1990, p.213-217, p.327-329. To perform the hardness test, a single piece is placed in the steel chamber of a durometer and then a steel piston pushes the dosage form until it ruptures, thereby measuring the applied force as a hardness measurement. Typically, 5 sheets from any one sample were tested to provide an average hardness value in kilograms.

Sweetness level

As used herein, "sweetness index" is a term used to describe the sweetness level of a disintegrating tablet portion, lozenge portion, or the entire dosage form relative to sucrose. Sucrose (defined as the standard) has a sweetness index of 1. For example, the sweetness index of several known sweetener compounds is listed below:

sorbitol 0.54-0.7

Dextrose 0.6

Mannitol 0.7

Sucrose 1.0

High fructose corn syrup 55% 1.0

Xylitol 1.0

Fructose 1.2-1.7

Cyclamate 30

Aspartame 180

Acesulfame potassium 200

Saccharin 300

Sucralose 600

Sweet protein 2000-

In one embodiment, the disintegrating tablet portion and/or the lozenge of the dosage form of the present invention has a sweetness index of less than about 0.6. If a higher sweetness is desired, the addition of a sweetener can increase the sweetness of the dosage form to at least about 0.9, such as at least about 1.0, at least about 1.5, or at least about 2.0.

Use of dosage forms

In one embodiment, the invention features a method of treating a disease comprising orally administering the dosage form described above, wherein the dosage form contains an amount of a pharmaceutically active agent effective to treat the disease. Examples of such conditions include, but are not limited to, pain (e.g., headache, migraine, sore throat, angina, back pain and myalgia), fever, inflammation, upper respiratory tract disorders (e.g., cough and congestion), infections (e.g., bacterial and viral infections), depression, diabetes, obesity, cardiovascular disorders (e.g., high cholesterol, hypertriglyceridemia and hypertension), gastrointestinal disorders (e.g., nausea, dysentery, irritable bowel syndrome and bloating), sleep disorders, osteoporosis and nicotine dependence.

In one embodiment, the method is for treating an upper respiratory disease, wherein the pharmaceutically active agent is selected from the group consisting of phenylephrine, cetirizine, loratadine, fexofenadine, diphenhydramine, dextromethorphan, chlorpheniramine, chlophedianol, and pseudoephedrine, and the hard sugar moiety comprises a pharmaceutically active agent selected from the group consisting of menthol, dyclonine, pectin, and benzocaine.

Examples of the invention

Specific embodiments of the present invention are shown by the following examples. The invention is not limited to the specific limitations shown in these examples.

Example 1: preparation of dextromethorphan-containing disintegrating tablet fraction

Part A: preparation of layered dextromethorphan

First, an aqueous solution containing the following three components was prepared: dextromethorphan hydrobromide (20 wt%), polyvinylpyrrolidone (1 wt%), and deionized water (79 wt%).

Then, 1.96kg of microcrystalline cellulose (Avicel PH 200 grade, commercially available from FMCCorporation, philiadelphia, PA) was loaded into a fluidized bed coater equipped with rotor (die-cutting) attachment (model Glatt GPCG 5/9, commercially available from Glatt Air technologies, Binzen, Germany). The microcrystalline cellulose was fluidized with a gas stream at 36 c and the above-described dextromethorphan hydrobromide solution was sprayed onto the microcrystalline cellulose at a rate of 80 g/min until the microcrystalline cellulose contained (by weight of the layered particles) about 40 wt% dextromethorphan hydrobromide.

And part B: preparation of coated layered dextromethorphan

A coating solution (total solution weight equal to 10.7kg) was prepared containing cellulose acetate 398-10 (commercially available from Eastman Chemical, Kingsport, TN) and Eudragit E-100 (commercially available from Rohm America, Piscataway, N.J.) in acetone: the solid content level of Eudragit (80: 20) was about 12%.

Then, 3kg of the granulate prepared in part a above was loaded into a rotor fluid bed coating machine (GlattGPCG model 5/9). The granules were then fluidized with a stream of air at 36 c and then the coating solution was sprayed onto the granules at a rate of 40 g/min until the drug granules contained approximately 20% by weight of the coating.

Example 2: preparation of dextromethorphan-containing disintegrating tablet fraction

Part A: preparation of a blend of disintegrating tablet portions

All materials shown in table 1 below (except for coated dextromethorphan) were manually sieved through a 30 mesh sieve. Then, 1.5kg of the resulting blend and coated dextromethorphan of example 1 were charged into a 4 quart V-blender and mixed for 5 minutes.

Table 1: components of tablet base blends

Equivalent to a 30mg dose of dextromethorphan hydrobromide. Coated dextromethorphan granules were prepared according to example 1.

And part B: preparation of concave disintegrating tablet portions

400g of the blend obtained from part A above was removed from the mixer and then tabletted on a rotary tablet press at 60rpm using 7/16 inch ultra deep convex tableting tooling to give a weight of 660mg and a hardness ranging from about 3 to about 7kp/cm²And a concave tablet having a thickness of about 0.3 to about 0.31 inches.

Part C: preparing planar disintegrating tablet part

400g of the blend obtained from part A above was removed from the mixer and then tabletted on a rotary tablet press at 60rpm using 7/16 inch flat tableting dies to obtain a weight of 660mg and a hardness ranging from about 3 to about 7kp/cm²And a tablet having a thickness of about 0.25 to about 0.26 inches.

And part D: preparation of convex disintegrating tablet part

400g of the blend obtained from part A above was removed from the mixer and then tabletted on a rotary tablet press at 60rpm using 7/16 inch ultra deep concave tableting dies to obtain a weight of 660mg and a hardness ranging from about 3 to about 7kp/cm²And a convex tablet having a thickness of about 0.3 to about 0.31 inches.

Example 3: preparation of hard candy comprising decocting and disintegratingDosage form with a core divided into pieces

A sugar hard candy portion solution comprising menthol was prepared using the following materials:

table 2: components of a partially blended boiled hard candy

Composition (I)	Percent (w/w)	Mg/hard candy part
			Isomaltose	97.54	975.4
Menthol (USP)	1.2	12
			Red pigment No. 40	0.01	0.1
Sucralose	0.25	2.5
			Citric acid (USP)	0.5	5
Cherry flavoring agent	0.5	5
			Deionized water	---	---
Total of	100	1000

500g isomaltose and 75g deionized water were mixed in a stainless steel jar and heated to 170 ℃ until the water evaporated. The mixture was then cooled to 140 ℃, and the red pigment, citric acid, sucralose, menthol, and cherry flavoring were added and mixed.

The compressed tablets from example 2, part B, were then placed in a stainless steel mold that covered the concave surface of the tablet. The mold also includes an injection port through which the flowable hard candy portion blend is allowed to wrap around the tablet at the belly band of the tablet without covering the concave surface of the tablet. The hard candy portion blend (which was still heated at 140 ℃) was filled into a plastic syringe and manually injected into the mold, which was then allowed to cool at room temperature for 15 minutes. The compressed core-filled hard candy dosage form is then removed from the mold. The resulting dosage form provides taste-masked systemic delivery of dextromethorphan (an antitussive) and local delivery of the antitussive alone (menthol).

Example 4: preparing a bilayer dosage form comprising a layered portion of boiled candy hard candy and a layered portion of disintegrating tablet

The hard candy portion blend of example 3 was prepared as described in the examples. When the hard candy portion blend was in a flowable state, it was deposited into a round stainless steel mold with two flat surfaces using a 10cc plastic syringe. The resulting hard candy portion was allowed to cool and harden at room temperature for approximately 15 minutes. The hard candy portion is then placed into a rubber mold. Approximately 30mg of powdered polyethylene glycol (PEG)3350 was uniformly dispersed along one surface of the hard candy portion.

The flat compressed tablet from example 2, part C was then placed on top of the hard candy part and the resulting dosage form was baked in an oven set at 80 ℃ for 30 minutes, allowing the PEG 3350 to melt and create adhesion between the compressed tablet layer and the hard candy part layer. The resulting bilayer dosage form was then allowed to cool at room temperature for 30 minutes and removed from the rubber mold.

Example 5: preparing a candy having a concave/convex shape comprising a boiled candy hard candy part layer and a disintegrating tablet part layer Interfacial bilayer dosage form

The hard candy portion blend of example 3 was prepared as described in the examples. While the hard candy portion is still in a flowable state, it is deposited into a round stainless steel mold with a convex surface (which in turn forms a hard candy portion with a concave surface). The hard candy portion was allowed to cool and harden at room temperature for approximately 15 minutes. The hard candy portion was then placed into a rubber mold with the concave surface facing upward. Approximately 30mg of polyethylene glycol (PEG)3350 (previously melted at 80 ℃ in a 50mL stainless steel container) was placed on the surface of the hard candy portion. The convex compressed tablet from example 2, part D, was then placed on top of the hard candy part so that the PEG could be displaced along the entire interface and create adhesion between the compressed tablet layer and the hard candy part layer. The bilayer dosage form was then allowed to cool at room temperature for 10 minutes and removed from the rubber mold.

Example 6: making pressed sugar hard candy part layers

All materials listed in table 3 below were manually sieved through a 30 mesh screen. 1.5kg of the resulting blend was placed in a 4 quart V-blender and mixed for 5 minutes.

Table 3: components of pressed hard candy partial blends

Composition (I)	Percent (w/w)	Mg/hard candy part
			Sorbitol	5.00	50.0
Compressible sucrose	92.75	927.5
			Menthol	1.00	10.0
Mint oil flavor agent	0.50	5.0
			Magnesium stearate	0.75	7.5
Total of	100.0	1000.0

Commercially available from Domino Specialty Ingredients (Baltimore, MD) 400g of the resulting blend was removed from the mixer and compressed on a rotary tablet press at 60rpm using 5/8 inch flat beveled edge (FFBE) compression tooling to provide flat tablets having a weight of 1000mg, a hardness in the range of not less than 15kp/cm2, and a thickness of about 0.20 inch.

Example 7: preparing a bilayer dosage form comprising a compressed sugar hard candy portion layer and a disintegrating tablet portion layer

The pressed hard candy portion of example 6 was placed into a rubber mold with the flat surface facing upward. Approximately 30mg of polyethylene glycol (PEG)3350 melted at 80 ℃ in a 50mL stainless steel vessel was placed on the surface of the hard candy portion. The planar tablet of example 2, part C was then placed over the hard candy portion such that the PEG was displaced along the interface to create adhesion between the compressed tablet layer and the hard candy portion layer. Then, the bilayer dosage form was cooled at room temperature for 10 minutes and removed from the rubber mold. The dosage form provides taste-masked systemic delivery of dextromethorphan (an antitussive) and local delivery of a separate antitussive (menthol).

Example 7: preparing a bilayer dosage form having a compressed disintegrating tablet portion and a compressed hard candy portion

All materials listed in table 4 below were manually sieved through a 30 mesh screen. 1.0kg of the resulting blend was charged to a 4 quart V-blender and mixed for 5 minutes.

Table 4: components of pressed hard candy layer blends

Composition (I)	Milligram/tablet	Gram/batch
			Compressible isomalt	630	899.6
Mint oil flavor agent	11	15.7
			Sucralose (NF)	1	1.4
Anhydrous sodium carbonate	20	28.6
			Sodium bicarbonate	10	14.3
Nicotine resin complex (20% nicotine)	20	28.6
			D&C Red No. 7 Ca lake (D)&C Red#7Ca Lake)	0.3	0.4
Magnesium stearate (NF)	8	11.4
			Total dragee layer	700.3	1000

Commercially available from Palatinit (Mannheim, Germany)

All materials listed in table 5 below were manually sieved through a 30 mesh screen. 0.32kg of the resulting blend was charged to a 1 quart V-blender and mixed for 5 minutes.

Table 5: components of a compression disintegration layer blend

Composition (I)	Milligram/tablet	Gram/batch
			Sucralose (NF)	1.5	2.1
Cinnamon flavor	4.5	6.3
			Cross-linked polyvinylpyrrolidone (NF)	15	21.1
Dextrose monohydrate	200	281.9
			Magnesium stearate (NF)	6	8.5
Total disintegrating tablet layer	227	320

The resulting blend was then removed from the mixer and tableted on a bi-layer rotary tablet press at 40rpm using 1/2 inch diameter lozenge tableting tooling dies to provide bi-layer tablets having a weight of about 927.3mg, a hardness range of not less than 15kp/cm2, and a thickness of about 0.3 inches.

Example 8: preparing a bilayer dosage form having a compressed disintegrating tablet portion and a compressed hard candy portion

All materials listed in table 6 below were manually sieved through a 30 mesh screen. 1.0kg of the resulting blend was charged to a 4 quart V-blender and mixed for 5 minutes.

Table 6: components of pressed hard candy layer blends

Composition (I)	Milligram/tablet	Gram/batch
			Compressible isomalt	839	559.3
Mint oil flavor agent	12	8.0
			Vanilla flavoring agent	1	0.7

Sucralose (NF)	1	0.7
			CaCO3 particles	631.6	421.1
FD&C blue No. 1 HT Al lake (FD)&C Blue#1HT Al Lake)	0.4	0.3
			Magnesium stearate (NF)	15	10.0
Total dragee layer	1500	1000

Commercially available from Palatinit (Mannheim, Germany)

Commercially available from Particle Dynamics Inc (st. louis, MO)

All materials listed in table 7 below were manually sieved through a 30 mesh screen. 0.10kg of the resulting blend was charged into a 1 quart V-blender and mixed for 5 minutes.

Table 7: components of a compression disintegration layer blend

Composition (I)	Milligram/tablet	Gram/batch
			Sucralose (NF)	2	0.6
Vanilla flavoring agent	2.5	0.8
			Polyethylene oxide (NF)	5	1.6
Cross-linked polyvinylpyrrolidone (NF)	20	6.3
			Taste-masked famotidine granules	86.55	27.2
Dextrose monohydrate-Cerelose 2033 grade	200	62.8
			Magnesium stearate (NF, Veg Source 2257 grade)	2.5	0.8
Total disintegrating tablet layer	318.55	100

Commercially available from McNeil CHC (Fort Washington, Pa.)

The resulting blend was then removed from the mixer and tableted with 5/8 inch diameter lozenge tableting dies on a bi-layer rotary tablet press at 40rpm to provide bi-layer tablets having a weight of about 1818.55mg, a hardness range of no less than 15kp/cm2, and a thickness of about 0.35 inch.

Example 9: preparing a bilayer dosage form having a compressed disintegrating tablet portion and a compressed hard candy portion

All materials listed in table 8 below were manually sieved through a 30 mesh screen. 1.0kg of the resulting blend was charged into a 4 quart V-blender and mixed for 5 minutes.

Table 8: components of pressed hard candy layer blends

Composition (I)	Milligram/tablet	Gram/batch
			Compressible isomalt	1363.6	906.0

Mint oil flavor agent	15	10.0
			Sucralose (NF)	1	6.6
Ibuprofen (USP)	100	66.5
			Benzocaine	5	3.3
FD&C blue No. 1 HT Al lake (FD)&C Blue#1HT Al Lake)	0.4	0.27
			Magnesium stearate (NF)	20	13.3
Total dragee layer	1505	1000

Commercially available from Palatinit (Mannheim, Germany)

All materials listed in table 9 below were manually sieved through a 30 mesh screen. 0.10kg of the resulting blend was charged into a 1 quart V-blender and mixed for 5 minutes.

Table 9: components of a compression disintegration layer blend

Composition (I)	Milligram/tablet	Gram/batch
			Sucralose (NF)	2	0.84
Vanilla flavoring agent	2.5	1.04
			Polyethylene oxide (NF)	2.5	1.04
Cross-linked polyvinylpyrrolidone (NF)	20	8.35
			Benzocaine (USP)	10	4.18
Dextrose monohydrate	200	83.51
			Magnesium stearate (NF)	2.5	1.04
Total disintegrating tablet layer	239.5	100

The resulting blend was then removed from the mixer and tableted on a bi-layer rotary tablet press at 40rpm using 5/8 inch diameter lozenge tableting tooling dies to provide bi-layer tablets having a weight of about 1744.5mg, a hardness range of not less than 15kp/cm2, and a thickness of about 0.30 inch.

Claims (26)

1. A dosage form consisting of both a disintegrating tablet portion and a hard candy portion, wherein:

(i) the disintegrating tablet portion comprises at least one pharmaceutically active agent, and

(ii) the hard candy portion covers at least 20% of the surface of the disintegrating tablet portion, and wherein the disintegration time of the hard candy portion is at least ten times longer than the disintegration time of the disintegrating tablet portion.

2. The dosage form of claim 1, whereinThe hardness of the disintegrating tablet portion is less than about 15kp/cm²And the hard candy portion has a hardness greater than about 15kp/cm²。

3. The dosage form of claim 1, wherein the pharmaceutically active agent contained in the disintegrating tablet portion is selected from the group consisting of: phenylephrine, dextromethorphan, pseudoephedrine, acetaminophen, ibuprofen, ketoprofen, loperamide, famotidine, calcium carbonate, simethicone, and menthol, and pharmaceutically acceptable salts thereof.

4. The dosage form of claim 1, wherein the pharmaceutically active agent is in the form of particles further coated with a taste-masking polymer, and wherein the particles have an average particle size of from about 50 microns to about 1000 microns.

5. The dosage form of claim 1, wherein the hard candy portion comprises a pharmaceutically active agent that is different from the pharmaceutically active agent comprised by the disintegrating tablet portion.

6. The dosage form of claim 5, wherein the pharmaceutically active agent contained in the hard candy portion is selected from the group consisting of: phenylephrine, dextromethorphan, pseudoephedrine, chlorpheniramine, methocarbamol, chlophedianol, ascorbic acid, menthol, pectin, dyclonine, and benzocaine, and pharmaceutically acceptable salts thereof.

7. The dosage form of claim 1, wherein the hard candy portion comprises at least 50% by weight of sugar selected from the group consisting of: isomalt, sucrose, dextrose, corn syrup, lactitol, and maltitol, and mixtures thereof.

8. The dosage form of claim 1, wherein the disintegrating tablet portion comprises at least 40% by weight of a compressible excipient selected from the group consisting of: isomalt, dextrose monohydrate, maltodextrin, lactose monohydrate, dextrin, mannitol, lactitol, sorbitol, xylitol, erythritol, sucrose, and lactose, and mixtures thereof.

9. The dosage form of claim 8, wherein the compressible excipient is in the form of particles having an average particle size of about 75 to about 400 microns.

10. The dosage form of claim 9, wherein the disintegrating tablet portion further comprises a water-swellable excipient selected from the group consisting of: sodium carboxymethyl starch, cross-linked polyvinylpyrrolidone, cross-linked carboxymethyl cellulose, microcrystalline cellulose, starch, hydroxypropyl cellulose, and alginic acid.

11. The dosage form of claim 9, wherein the weight ratio of the compressible excipient to the water swellable excipient is from about 10: 1 to about 100: 1.

12. The dosage form of claim 7, wherein the disintegrating tablet portion further comprises an effervescent couple comprising one member selected from the group consisting of sodium bicarbonate, potassium bicarbonate, calcium carbonate, magnesium carbonate, and sodium carbonate and one member selected from the group consisting of citric acid, malic acid, fumaric acid, tartaric acid, and alginic acid.

13. The dosage form of claim 1, wherein the weight ratio between the disintegrating tablet portion and the hard candy portion is from about 10: 90 to about 60: 40.

14. The dosage form of claim 1, wherein the hard candy portion covers at least 50% of the surface area of the disintegrating tablet portion.

15. The dosage form portion of claim 14, wherein the hard candy portion comprises a plurality of openings that expose the surface area of the disintegrating tablet portion.

16. The dosage form of claim 14, wherein the hard candy portion covers substantially all of the surface area of the disintegrating tablet portion, and wherein the hard candy portion further comprises a plurality of indentations adapted to dissolve upon contact with the intraoral fluid and expose the surface area of the disintegrating tablet portion.

17. The dosage form of claim 1, wherein the disintegrating tablet portion has multiple layers comprising at least one different ingredient.

18. The dosage form of claim 17, wherein the disintegrating tablet portion comprises two layers, wherein the first layer comprises the pharmaceutically active agent and the second layer comprises a second pharmaceutically active agent that may be different from the pharmaceutically active agent contained within the first layer.

19. The dosage form of claim 17, wherein the disintegrating tablet portion comprises two layers, wherein both the first layer and the second layer comprise the pharmaceutically active agent, and wherein the pharmaceutically active agent in the second layer is coated with a sustained release coating.

20. The dosage form of claim 17, wherein both the first layer and the second layer are exposed on a surface of the dosage form.

21. The dosage form of claim 1, wherein the dosage form has a multilayer structure, wherein the disintegrating tablet portion is a first layer and the hard candy portion is a second layer.

22. The dosage form of claim 21, wherein the surface of one layer has a convex shape and the surface of the other layer has a concave shape.

23. The dosage form of claim 21, further comprising a third layer disposed between a surface of the first layer and a surface of the second layer, wherein the third layer comprises an edible binder-like material.

24. The dosage form of claim 23, wherein the edible binder-like material comprises an ingredient selected from the group consisting of: polyethylene glycol, polyethylene oxide, polycaprolactone, carnauba wax, microcrystalline wax, opanols, shellac wax, and beeswax.

25. A method of treating a disease comprising orally administering the dosage form of claim 1, wherein the dosage form comprises the pharmaceutically active agent in an amount effective to treat the disease.

26. The method of claim 25, wherein the disintegrating tablet portion comprises at least one pharmaceutically active agent selected from the group consisting of: phenylephrine, dextromethorphan, chlorpheniramine, chlophedianol, and pseudoephedrine, and the hard candy moiety comprises at least one pharmaceutically active agent selected from the group consisting of: menthol, nicotine, dyclonine, pectin, and benzocaine.