The invention provides a rapidly disintegrating tablet comprising an active ingredient, a water soluble, directly compressible carbohydrate, and a water soluble, directly compressible filler. Also provided is a method of producing a rapidly disintegrating tablet, which method comprises wet granulating a mixture comprising a directly compressible, water soluble carbohydrate, a directly compressible, water insoluble filler, a beneficial ingredient, and a solvent, and compressing the granulate to produce the tablet.

BRIEF SUMMARY OF THE INVENTION

The present invention provides a compressed rapidly disintegrating tablet comprising a beneficial ingredient, which is incorporated into a matrix comprising a water soluble, directly compressible carbohydrate, and a water insoluble, directly compressible filler. The tablet of the present invention has low friability (e.g., less than about 1.5%), high porosity (e.g., from about 15% to about 45%), and disintegrates rapidly in water (e.g., from within about 2 seconds to within about 120 seconds).

The present invention further provides a method of producing a rapidly disintegrating tablet. The method preferably comprises wet granulating a water soluble carbohydrate and a water insoluble filler in the presence of a beneficial ingredient and a solvent, to form a wet granulate. The wet granulate is dried, to produce a dry granulate comprising the beneficial ingredient, the water soluble carbohydrate and the water insoluble filler, and compressed to produce a rapidly disintegrating tablet. The wet granulate and/or dry granulate typically is blended with other ingredients prior to compression.

DETAILED DESCRIPTION OF THE INVENTION

The present invention provides a rapidly disintegrating tablet comprising a beneficial ingredient; a directly compressible, water soluble carbohydrate; and a directly compressible, water insoluble filler. Preferably, the tablet of the present invention has a friability of at most about 1.5% and a porosity of from about 15% to about 45%, e.g., from about 15% to about 35%, from about 15% to about 25%, from about 20% to about 35% (e.g., from about 21% to about 32%), from about 20% to about 30%, or from about 20% to about 25% (e.g., from about 21% to about 23%). Preferably, the disintegration time of the tablet of the present invention is within about 120 seconds or less.

The term "rapidly disintegrating" or "rapidly disintegrable" as used herein refers to the ability of a tablet (e.g., a tablet for oral administration) to disintegrate rapidly when contacted with a fluid, particularly an aqueous fluid (e.g., water, bodily fluids (e.g., saliva), and the like), to form a suspension, slurry or dispersion, which facilitates administration of the contents of the tablet (e.g., by forming a suspension, slurry or dispersion, which is easily swallowed).

In a preferred embodiment, the tablet of the present invention is an orally disintegrating tablet, which disintegrates rapidly when contacted with an aqueous fluid (e.g., water or saliva), to form a suspension, slurry or dispersion, which can be easily swallowed. The orally disintegrating tablet of the present invention preferably disintegrates rapidly in the oral cavity when contacted with saliva, to form a suspension, slurry or dispersion, which can be easily swallowed. In one embodiment, the tablet of the present invention is a taste-masked orally disintegrating tablet (e.g. a rapidly disintegrating tablet as described herein, which includes a taste-making agent, an osmotic agent, and the like, or a combination thereof). The term "oral cavity" includes the region within the interior of the mouth, including, but not limited to, the buccal cavity (e.g., anterior to the teeth and gums) as well as the sublingual and supralingual spaces, and the like.

The tablet of the present invention preferably disintegrates within about 120 seconds or less, when contacted with an aqueous fluid (e.g., water, saliva, or a buffered solution), to form a slurry, a dispersion or a suspension, which can be administered (e.g., swallowed) easily. The disintegration time of the tablet of the present invention can range from within about 2 seconds to within about 120 seconds, e.g., from within about 2 seconds to within about 60 seconds, or from within about 2 seconds to within about 30 seconds, as measured in by the Standard USP Disintegration Test for Sublingual Tablets. The tablet of the present invention more preferably disintegrates from within about 2 seconds to within about 30 seconds, and still more preferably from within about 2 seconds to within about 20 seconds, and most preferably from within about 2 seconds to within about 10 seconds (e.g., from within about 5 seconds to within about 10 seconds, or from within about 5 seconds to within about 8 seconds), as measured in by the Standard USP Disintegration Test for Sublingual Tablets.

When the tablet of the present invention is an orally disintegrating tablet, it preferably can disintegrate completely in the oral cavity within about 120 seconds, and more preferably from within about 2 seconds to within about 120 seconds (e.g., from within about 2 seconds to within about 60 seconds, or from within about 2 seconds to within about 30 seconds), when contacted with saliva, to form a slurry, a dispersion or a suspension, which can be swallowed easily. The orally disintegrating tablet of the present invention most preferably disintegrates completely in the oral cavity from within about 2 seconds to within about 20 seconds, when contacted with saliva, to form a slurry, a dispersion or a suspension, which can be swallowed easily.

The tablet of the present invention can be used as a delivery system for the administration of one or more beneficial ingredients. Any suitable beneficial ingredient can be used in accordance with the present invention. Suitable beneficial ingredients can include, for example, pharmaceutically active agents, nutraceutically active agents, breath fresheners (e.g., mints, such as peppermint, spearmint, etc.), confectionary products (e.g., candy, flavored products, etc.), and the like, and combinations thereof.

Pharmaceutically active agents can include, for example, medicaments or drugs, e.g., analgesics, anti-inflammatory agents, anthelmintics, anti-arrhythmic agents, antibiotics, anticoagulants, antidepressants, antidiabetic agents, antidiarrheal agents, antiemetic agents, antiepileptics, antihistamines, antihypertensive agents, antimuscarinic agents, antimycobacterial agents, antineoplastic agents, immunosuppressants, antithyroid agents, anti-tussive agents, antiviral agents, anxiolytic sedatives, astringents, beta-adrenoceptor blocking agents, cardiac inotropic agents, corticosteroids, cough suppressants, diagnostic agents, diagnostic imaging agents, diuretics, dopaminergics, haemostatics, immuriological agents, lipid regulating agents, muscle relaxants, parasympathomimetics, parathyroid calcitonin and biphosphonates, prostaglandins, radio-pharmaceuticals, steroids, anti-allergic agents, stimulants and anoretics, sympathomimetics, thyroid agents, vasodilators, xanthines, and the like, and mixtures thereof. Exemplary pharmaceutically active agents include, e.g., mirtazapine, olanzapine, ondansetron, NSAIDs, acetaminophen, enalapril, famotidine, fluoxetine, lorazepam, loperamide, loratidine, narcotic analgesics, e.g., morphine, hydrocodone, and the like, oxazepam, piroxicam, rizatriptan, zolmitriptan, zolpidem, hyoscyamine and salts thereof, e.g., hyoscyamine sulfate, and the like.

Nutraceutically active agents can include, for example, dietary supplements, minerals, vitamins, and the like, and combinations thereof. Exemplary nutraceutically active agents include, e.g., vitamin A, vitamin D, vitamin E (e.g., d-.alpha.-tocopherol, d-.alpha.-tocopheryl acetate, dl-a-tocopherol and dl-.alpha.-tocopheryl acetate), vitamin B1 and derivatives thereof, vitamin B2 and derivatives thereof, vitamin B6 and derivatives thereof (e.g., pyridoxine hydrochloride), vitamin C and derivatives thereof (e.g., ascorbic acid, sodium L-ascorbate, etc.), vitamin B12 and derivatives thereof, fluoride (e.g., sodium fluoride), calcium, magnesium, iron, proteins, amino acids, oligosaccharides, and the like, and mixtures thereof. It will be appreciated that there may be circumstances in which a pharmaceutically active agent also may function as a nutraceutically active agent, and in which a nutraceutically active agent also may function as a pharmaceutically active agent.

Beneficial ingredients also can include, for example, detergents, foaming agents, anti-foaming agents, agriculturally beneficial products (e.g., fertilizers, pesticides, antimicrobial agents, herbicides, etc.), and the like, and combinations thereof. It will be appreciated that the beneficial agent also can include one or more of the additional ingredients in the tablet of the present invention, e.g., the directly compressible, water soluble carbohydrate, the directly compressible, water insoluble filler, and the like.

The tablet of the present invention can include any suitable amount of the beneficial agent, which is preferably an effective amount. When the beneficial agent is a pharmaceutically active agent, the effective amount of the pharmaceutically active agent preferably is a therapeutically or pharmaceutically effective amount. When the beneficial agent is a nutraceutically active agent, the effective amount of the nutraceutically active agent preferably is a nutraceutically effective amount. Any suitable dosage level of a pharmaceutically active agent or a nutraceutically active can be employed in the tablet of the present invention. The dose to be administered to an animal, particularly a human, in accordance with the present invention should be sufficient to effect a prophylactic or therapeutic response in the animal over a reasonable time frame. One skilled in the art will recognize that the amount of active ingredient will vary depending upon a variety of factors including, for example, the activity of the specific compound employed; the age, body weight, general health, sex, and diet of a particular patient or patient population; the time of administration, rate of absorption, and rate of excretion; the potential interactions with other drugs taken separately or in combination; and the severity of the particular disease or condition for which a therapeutic effect is desired. The size of the dose will also be determined by the existence, nature, and extent of any adverse side effects that might accompany the administration of a particular compound. Other factors, which affect the specific dosage, include, for example, bioavailability, metabolic profile, and the pharmacodynamics associated with the particular compound to be administered in a particular patient.

For example, a pharmaceutically effective amount can include the amount or quantity of a pharmaceutically active agent, which is sufficient to elicit the required or desired therapeutic response, e.g., an amount, which is sufficient to elicit a biological or therapeutic response when administered to a patient. A nutraceutically effective amount can include an amount or quantity of a nutraceutically active agent, which is sufficient to elicit a nutritive response when administered to a patient. A nutraceutically effective amount can include, for example, an amount that constitutes at least about 10% of the United States Recommended Daily Allowance ("RDA") of a particular nutraceutical ingredient for a patient. For a mineral or vitamin, for example, a nutraceutically effective amount also can include as much as about 100% or more of the applicable RDA.

The amount of active ingredient in the tablet of the present invention also can be expressed in terms of a weight percentage. For example, the active ingredient in the tablet of the present invention can constitute from greater than 0% to about 80% by weight based on the total weight of the tablet, or from greater than 0% to about 60% by weight based on the total weight of the tablet. The amount of active ingredient in the tablet of the present invention also can be expressed in terms of total mass per tablet. For example, the tablet of the present invention can include an active ingredient in an amount of from about 1 .mu.g to about 2 g per tablet, or from about 0.01 mg and about 1000 mg per tablet. For example, the tablets of the present invention can include one or more active ingredients in amounts that range, e.g., from about 0.1 mg to about 0.5 mg, from about 1 mg to about 20 mg (e.g., 2 mg, 8 mg, 15 mg), from about 50 mg to about 100 mg (e.g., 80 mg), from about 100 mg to about 500 mg (e.g., 100 mg, 200 mg, 250 mg, 300 mg), or from about 500 mg to about 1000 mg.

Directly compressible excipients are well known in the art, and have been characterized by their ability to bond to other materials to form a strong compact. Any suitable directly compressible, water soluble carbohydrate can be used in the tablet of the present invention. Suitable directly compressible, water soluble carbohydrates can include, for example, directly compressible, water soluble sugars and directly compressible, water soluble sugar alcohols.

Preferred directly compressible, water soluble carbohydrates include, for example, directly compressible mannitol, directly compressible sorbitol, directly compressible maltitol, directly compressible lactose, directly compressible sucrose, directly compressible xylose, directly compressible trehalose, directly compressible dextrose, and the like, and combinations thereof. Preferred directly compressible, water soluble carbohydrates include directly compressible mannitol, which is preferably a directly compressible spray dried mannitol. The tablet of the present invention most preferably comprises a directly compressible granulate obtained by wet granulation of a directly compressible spray dried mannitol. The directly compressible granulate preferably is obtained by wet granulation of a directly compressible spray dried mannitol in the presence of a solution, dispersion or slurry comprising a solvent, and more preferably is obtained by wet granulation of a directly compressible spray dried mannitol in the presence of a solution, dispersion or slurry comprising the active ingredient and a solvent. In a preferred embodiment, the directly compressible granulate is obtained by wet granulation of a directly compressible spray dried mannitol in the presence of the active ingredient and an aqueous solvent, which aqueous solvent is most preferably water.

The wet granulation can be performed by adding a granulating solvent to a dry mixture of a directly compressible, water soluble carbohydrate and a beneficial ingredient, and granulating the resulting composition. Alternatively, the wet granulation can be performed by adding a granulation solvent, which is a solution, slurry or dispersion of a beneficial ingredient and a solvent, to a directly compressible, water soluble carbohydrate, and granulating the resulting composition. In a particularly preferred embodiment, the solvent is aqueous (e.g., water) and the water soluble carbohydrate is a spray-dried mannitol. For example, the directly compressible granulate can be obtained by adding a solution, slurry or dispersion of a beneficial agent and water, to a directly compressible spray dried mannitol, and granulating the resulting composition. Alternatively, the directly compressible granulate can be obtained by adding water, to a dry mixture of a directly compressible spray dried mannitol and a beneficial ingredient, and granulating the resulting composition.

When a directly compressible spray-dried mannitol is used in the tablet of the present invention, the directly compressible spray-dried mannitol preferably comprises crystalline particles having a substantially rounded shape. It is further preferred that, when a directly compressible spray dried mannitol is used, the directly compressible spray dried mannitol comprises particles having a diameter of from about 20 .mu.m to about 200 .mu.m, and more preferably from about 50 .mu.m to about 175 .mu.m, and still more preferably from about 75 .mu.m to about 150 .mu.m. In a preferred embodiment, the directly compressible spray-dried mannitol comprises crystalline mannitol particles having a substantially rounded shape, wherein about 40% to about 80% of the spray dried mannitol particles have a diameter of from about 20 .mu.m to about 200 .mu.m. In a particularly preferred embodiment, the directly compressible spray-dried mannitol comprises crystalline mannitol particles having a substantially rounded shape, wherein about 60% of the particles of the spray dried mannitol have a diameter of from about 75 .mu.m to about 150 .mu.m.

The directly compressible, water soluble carbohydrate can be present in the tablet of the present invention in any suitable amount, e.g., in an amount of from about 1% by weight to about 99% by weight based on the total weight of the tablet. Preferably, the directly compressible, water soluble carbohydrate is present in an amount of from about 30% by weight to about 95% by weight based on the total weight of the tablet, and more preferably from about 60% by weight to about 85% by weight based on the total weight of the tablet.

Any suitable directly compressible, water insoluble filler can be used in accordance with the present invention. Suitable directly compressible, water insoluble fillers can include, for example, directly compressible water insoluble celluloses (e.g., microcrystalline cellulose), directly compressible water insoluble cellulose derivatives (e.g., ethyl cellulose), and the like. Preferably, the directly compressible, water insoluble filler is a directly compressible, water insoluble cellulose, which is most preferably microcrystalline cellulose. A preferred directly compressible microcrystalline cellulose, which can be used in accordance with the present invention, has a bulk density of from about 0.2 g/cm3 to about 0.4 g/cm3, e.g., about 0.3 g/cm3. The mean particle size of the directly compressible microcrystalline cellulose used in accordance with the present invention preferably is from about 20 .mu.m to about 200 .mu.m.

The directly compressible, water insoluble filler can be present in the tablet of the present invention in any suitable amount, e.g., in an amount of from about 1% by weight to about 40% by weight based on the total weight of the tablet. Preferably, the directly compressible, water insoluble filler is present in an amount of from about 10% by weight to about 30% by weight based on the total weight of the tablet, and is more preferably present in an amount of from about 15% by weight to about 20% by weight based on the total weight of the tablet.

The friability of the tablet of the present invention preferably is at most about 1.5%, but is more preferably at most about 1%, and is most preferably at most about 0.5% (e.g., about 0.1% or about 0.2%).

Hardness refers to the diametral breaking strength as measured by conventional pharmaceutical tablet hardness determination methods, which are well known in the art. A higher hardness value, sometimes measured in Newtons (N), generally is indicative of a higher diametral strength. The hardness of the tablet of the present invention preferably ranges from about 10 N to about 47 N, and more preferably from about 14 N to about 35 N, and most preferably from about 21 N to about 28 N.

The term "porosity" is used herein as a measurement, which is indicative of the amount of internal void space remaining in the tablet after compression, and is measured as a percentage of the pore volume (or void space) relative to the total tablet volume. The porosity of the tablet of the present invention preferably is from about 15% to about 45%, e.g., from about 15% to about 35%, from about 15% to about 25%, from about 20% to about 35% (e.g., from about 21% to about 32%), from about 20% to about 30%, or from about 20% to about 25% (e.g., from about 21% to about 23%). The porosity of the tablet of the present invention is believed to be relatively high as compared to other conventional compressed rapidly disintegrating tablets. The high porosity of the tablet of the present invention is believed to promote rapid disintegration upon contact with saliva in the oral cavity, to form a suspension, slurry or dispersion, which can be swallowed easily without water or mastication.

The tablet of the present invention can have any suitable exterior surface area, e.g., from about 0.10 square inches to about 2.0 square inches, e.g., from about 0.1 square inches to about 1.0 square inches, from about 0.1 square inches to about 0.5 square inches, from about 0.1 square inches to about 0.3 square inches, from about 0.1 to about 0.2 square inches. Preferably, the tablet of the present invention has an exterior surface area of from about 0.30 square inches to about 1.0 square inches (e.g., from about 0.50 square inches to about 1.0 square inches), and more preferably has an exterior surface area of from about 0.50 square inches to about 0.80 square inches. The tablet of the present invention also can have any suitable density, which is a measure of mass per unit volume and is expressed in terms of grams per milliliter (g/mL). The density of the composition can range from about 0.5 g/mL to about 2.5 g/mL, but is preferably from about 0.7 g/mL to about 2.0 g/mL, and is more preferably from about 0.7 g/mL to about 1.5 g/mL (e.g., from about 1.1 g/mL to about 1.5 g/mL (e.g., from 1.1 g/mL to 1.3 g/mL)).

The tablet of the present invention preferably includes one or more additional ingredients selected from the group consisting of disintegrants, lubricants, water soluble fillers, water insoluble fillers, and the like, and combinations thereof. The tablet of the present invention optionally can include surface active agents, taste masking agents, flavorants, sweeteners, colorants, and the like, and combinations thereof.

Suitable disintegrants can include, for example, microcrystalline cellulose, sodium carboxymethyl cellulose, calcium carboxymethyl cellulose, modified cellulose gum, crospovidone, alginic acid and alginates, pregelatinized starch, sodium starch glycollate, modified corn starch, starch (e.g. potato/maize starch), and the like, and combinations thereof.

Suitable surface active agents can include, for example, sodium dodecyl sulfate, sodium lauryl sulfate, polyoxyethylene sorbitan fatty acid esters (Tweens), polyoxyethylene stearates, sorbitan fatty acid esters (Spans), and the like, and combinations thereof.

Suitable lubricants can include, for example, stearates (e.g. stearic acid, magnesium stearate, zinc stearate, calcium stearate, and the like), talc, polyethylene glycol, liquid paraffin, sodium lauryl sulfate, magnesium lauryl sulfate, colloidal silicon dioxide, palmitostearate, vegetable oil, hydrogenated vegetable oil, and the like, and combinations thereof.

Suitable fillers can include, for example, lactose, granular sugars, confectioners sugar, dextrose, mannitol, sorbitol, xylitol, calcium carbonate, magnesium carbonate, calcium phosphate, calcium sulfate, microcrystalline cellulose, powdered cellulose, pregelatinized starch, starch, magnesium trisilicate, aluminum hydroxide, and the like, and combinations thereof.

Suitable flavorants can include, for example, flavors, which are known to those of skill in the art, such as, for example, natural flavors, artificial flavors, and combinations thereof. Flavorants may be chosen, e.g., from synthetic flavor oils and flavoring aromatics and/or oils, oleoresins, extracts derived from plants, leaves, flowers, fruits, and the like, and combinations thereof. Non-limiting examples of flavor oils include spearmint oil, cinnamon oil, oil of wintergreen (methyl salicylate), peppermint oil, clove oil, bay oil, anise oil, eucalyptus oil, thyme oil, cedar leaf oil, oil of nutmeg, allspice, oil of sage, mace, oil of bitter almonds, and cassia oil. Suitable flavoring agents also include, for example, artificial, natural and synthetic fruit flavors such as vanilla, citrus oils (e.g., lemon, orange, lime, and grapefruit), and fruit essences (e.g., apple, pear, peach, grape, strawberry, raspberry, cherry, plum, pineapple, and apricot), and the like, and combinations thereof. The flavoring agents may be used in liquid or solid form and, as indicated above, may be used individually or in admixture. Other flavorants can include, for example, certain aldehydes and esters, e.g., cinnamyl acetate, cinnamaldehyde, citral diethylacetal, dihydrocarvyl acetate, eugenyl formate, p-methylamisol, and the like, and combinations thereof.

Suitable sweeteners can include, for example, solid natural or synthetic sweeteners, e.g., amino acid and dipeptide based sweeteners, e.g., glycerrhizin, saccharin and its salts, aspartame, and the like, and combinations thereof.

Suitable colorants can include, for example, red, black and yellow iron oxides; FD & C dyes (e.g., FD & C blue No. 2, FD & C red No. 40); and the like, and combinations thereof.

The present invention further provides a process for producing a rapidly disintegrating tablet, which method includes: (i) wet-granulating a directly compressible, water soluble carbohydrate and a directly compressible, water insoluble filler in the presence of a beneficial ingredient and a solvent, to produce a wet granulate comprising the beneficial ingredient, the directly compressible, water soluble carbohydrate and the directly compressible, water insoluble filler; (ii) drying the wet granulate, to produce a dry granulate; (iii) adding one or more ingredients selected from the group consisting of disintegrants, lubricants, water soluble fillers, water insoluble fillers, and the like, and combinations thereof; (iv) optionally adding one or more ingredients selected from the group consisting of surface active agents, flavorants, sweeteners, colorants, and the like, and combinations thereof; and, (v) compressing, to form the tablet. Suitable directly compressible, water soluble carbohydrates include the directly compressible, water soluble carbohydrates as described herein. Directly compressible, water soluble carbohydrate can include, for example, directly compressible mannitol, directly compressible sorbitol, directly compressible maltitol, directly compressible lactose, directly compressible sucrose, directly compressible xylose, directly compressible trehalose, directly compressible dextrose, and combinations thereof.

Preferably, the directly compressible, water soluble carbohydrate is directly compressible mannitol, e.g., directly compressible spray dried mannitol as described herein. For example, when a directly compressible spray-dried mannitol is used, the directly compressible spray dried mannitol may comprise particles having a diameter of from about 20 .mu.m to about 200 .mu.m, e.g., from about 50 .mu.m to about 175 .mu.m, or from about 75 .mu.m to about 150 .mu.m. The spray dried mannitol can comprise crystalline mannitol particles having a substantially rounded shape, wherein about 40% to about 80% of the spray dried mannitol particles have a diameter of from about 20 .mu.m to about 200 .mu.m. In a particularly preferred embodiment, the directly compressible, spray-dried mannitol comprises crystalline mannitol particles having a substantially rounded shape, wherein about 60% of the particles of the spray dried mannitol have a diameter of from about 75 .mu.m to about 150 .mu.m.

Preferably the water insoluble filler is a directly compressible polysaccharide as described herein. For example, the directly compressible polysaccharide can include a directly compressible, water insoluble cellulose, e.g., microcrystalline cellulose. The directly compressible microcrystalline cellulose can have a bulk density, e.g., of from about 0.2 g/cm3 to about 0.4 g/cm3, e.g., about 0.3 g/cm3. The mean particle size of the directly compressible microcrystalline cellulose used in accordance with the present invention can be from about 20 .mu.m to about 200 .mu.m.

The granulating solvent, which can be used for carrying out the wet granulation step in accordance with the method of the present invention, can be any suitable solvent, but is preferably an aqueous solvent, such as water or a mixture of water and another solvent. Most preferably, the granulating solvent is water. In a particularly preferred embodiment, the directly compressible granulate is prepared by wet granulating a mixture comprising a directly compressible, water soluble carbohydrate; a directly compressible, water insoluble filler, and, as a granulation solvent, a solution, dispersion or slurry of a beneficial ingredient in water. In another particularly preferred embodiment, the wet granulate is prepared by adding water as a granulation solvent to a mixture comprising a directly compressible, water soluble carbohydrate; a directly compressible, water insoluble filler; and a beneficial ingredient, and granulating the resulting composition.

The shape and size of the tablet of the present invention is not limited to any particular shape or size. Examples of suitable shapes include triangle, square, round, cylinder, animal-shape, irregular shape (Caplet-type), ring (donut shape), flat-faced tablet, biconvex tablet, multi-layer tablet, and the like. In addition, letters or characters may be debossed or embossed on the tablet.
 

Claim 1 of 39 Claims

1. A rapidly disintegrating tablet comprising a compressed granulate containing: (i) one or more beneficial ingredients; (ii) one or more directly compressible, water soluble carbohydrates; and (iii) one or more directly compressible, water insoluble fillers, wherein the tablet has a friability of at most about 1.5%, and a porosity of from about 15% to about 45%, wherein the tablet disintegrates rapidly in an aqueous medium.

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