Title of Invention	A PROCESS TO OBTAIN A PHARMACEUTICAL PRODUCT WITH AN ENHANCED DISSOLUTION RATE AND THE PHARMACEUTICAL PRODUCT RESULTING THEREOF
Abstract	The object of present invention is to provide a process and pharmaceutical products, preferably tablets, made from said process for enhancement of dissolution rate of sparingly soluble drugs leading to their increased bioavailability. Grains of solid dispersion of the drug in water soluble carrier are formed/cemented into tablets in a manner as in a cube sugar. Solid dispersions of drugs in carriers of poor compressibility can be easily formed into tablets of any suitable shape/size by known cube sugar technology. The tablets made from the process of the present invention will not only be readily dispersible owing to capillary action but also ensure rapid dissolution of poorly soluble drug because of solid dispersion. Simultaneous exploitation of well-known approaches- solid dispersion, capillary action, optional surfactant and optional size reduction in the proposed technique will obviously result in steep enhancement of dissolution rate without compromising with content uniformity.

Title of Invention

A PROCESS TO OBTAIN A PHARMACEUTICAL PRODUCT WITH AN ENHANCED DISSOLUTION RATE AND THE PHARMACEUTICAL PRODUCT RESULTING THEREOF

Abstract

The object of present invention is to provide a process and pharmaceutical products, preferably tablets, made from said process for enhancement of dissolution rate of sparingly soluble drugs leading to their increased bioavailability. Grains of solid dispersion of the drug in water soluble carrier are formed/cemented into tablets in a manner as in a cube sugar. Solid dispersions of drugs in carriers of poor compressibility can be easily formed into tablets of any suitable shape/size by known cube sugar technology. The tablets made from the process of the present invention will not only be readily dispersible owing to capillary action but also ensure rapid dissolution of poorly soluble drug because of solid dispersion. Simultaneous exploitation of well-known approaches- solid dispersion, capillary action, optional surfactant and optional size reduction in the proposed technique will obviously result in steep enhancement of dissolution rate without compromising with content uniformity.

Full Text	FIELD OF INVENTION Present invention relates to a process and pharmaceutical products, preferably tablets, made from said process for enhancement of dissolution rate of sparingly soluble drugs leading to their increased bioavailability. Known phenomena/techniques of solid dispersion, capillary action, optional surfactant and optional size reduction have been simultaneously exploited for enhancement of dissolution rate leading to improved bioavailabilty. The tablets made from the process of the present invention also exhibit improved content uniformity. BACKGROUND OF INVENTION Dissolution rate of drug plays a prime role in controlling the absorption of the drug from the dosage form. When a drug is administered orally in solid dosage form (such as tablets or capsules), it is designed to undergo series of predetermined stages. The first step towards the absorption process is the disintegration of the dosage form. The second and in fact the slowest or rate-limiting step is found to be dissolution of drug in the fluid at the absorption site. When dissolution is the controlling step in the overall process, absorption is said to be dissolution rate limited. Since the rate-limiting step in the absorption process is dissolution step, therefore, any factor influencing the rate of dissolution must also influence the rate of absorption. According to dissolution theory, two important parameters determining the dissolution rate are the solubility of the drug in the dissolution medium and the surface area of the drug exposed to the medium. The fact that more than 40 % of newly discovered drugs have little or no water solubility presents a serious challenge to the successful development and commercialization of new drugs in the pharmaceutical industry. No matter how active or potentially active a new molecular entity (NME) is against a particular molecular target, if the NME is not available in solution at the site of action, it is not a viable developmental candidate. As a result, the development of many exciting NMEs stopped before their potential was realized or confirmed because pharmaceutical companies cannot afford to conduct rigorous preclinical and clinical studies on a molecule that does not have a sufficient phamacokinetic profile due to poor water solubility. Though numerous techniques of diverse nature such as size reduction, complexation, reduction of hydrophobicity, polymorphic and crystal form, salt formation, adsorption, solid dispersion and freeze-drying have been developed for enhancement of dissolution rate but with limited success. Hence improvement of dissolution rate of sparingly soluble drugs still remains a challenge for scientific community. Solid dispersion is a well known approach for improvement of the dissolution rate and bioavailability of drugs that are poorly water-soluble. It is a dispersion of one or more active ingredients at molecular to microcrystalline level in an inert carrier or matrix at solid state. The carriers used have been physiologically inert compounds that are readily water soluble or water insoluble for fast or controlled dissolution respectively. To achieve faster dissolution rate of poorly water-soluble drug, the drug is dispersed at molecular level in a rapidly water soluble inert carrier to form a solid dispersion. Successful dispersion of the drug in the carrier at molecular level leads to formation of homogeneous phase of the solid dispersion. When such a product comes in contact with gastric fluid, then the water soluble carrier rapidly dissolves resulting in immediate release of the drug at the desired molecular level to cause dissolution with consequent improvement of bioavailability. Solid dispersions have been extensively studied for improvement of dissolution rate and numerous techniques of diverse nature have been developed for preparation of the same. These include hot melt extrusion, solvent method, fusion, supercritical fluid process, solvent-melting method and spray congealing. Solid dispersions offer numerous advantages as per the following: * Presence of the drug at molecular level to microcrystalline level in the carrier. * Rapid dissolution rate. * Transformation of low dose liquid drug into a solid form. * Minimization of polymorphic changes and thereby bioavailability problems * Excellent content uniformity. * Possibilities to controlled or sustain release by the use of low solubility carriers. In spite of numerous advantages and extensive work very few products based upon solid dispersions have been successfully commercialized. Major limitations for use of solid dispersions in the tablet form are attributable to poor compressibility of the carriers and scale up of the manufacturing process. Encapsulation of the solid dispersions in the hard gelatin capsules, on the other hand, delays the dissolution process of the drug because dissolution process will not start till the capsule shell has disintegrated to allow solid dispersion to come in contact with the gastric fluid. Moreover, gelatin capsule shells are susceptible to denaturation. Novel improved tablets have been conceptualized in the present invention for overcoming of aforementioned limitations of solid dispersions simply by forming fine crystals/grains/particles of solid dispersion of the drug(s) directly into tablets in a manner similar to that adopted for cube sugar production. Solid dispersions of drugs in carriers of poor compressibility can be easily formed into tablets of any suitable shape/size by known cube sugar technology. Resulting tablets will not only be readily dispersible owing to capillary action but also ensure rapid dissolution of poorly soluble drug because of solid dispersion. Surfactant can also be incorporated in the solid dispersion for further enhancement of dissolution rate. Simultaneous exploitation of well-known approaches- solid dispersion, capillary action, optional surfactant and optional particle size reduction will obviously result in steep enhancement of dissolution rate without compromising with content uniformity. SUMMARY OF THE INVENTION The object of present invention is to provide a process and pharmaceutical products, preferably tablets, made from said process for enhancement of dissolution rate of sparingly soluble drugs leading to their increased bioavailability. Simultaneous exploitation of well-known approaches- solid dispersion, capillary action, optional surfactant and optional size reduction in the proposed technique will obviously result in steep enhancement of dissolution rate without compromising with content uniformity. DISCLOSURE OF THE INVENTION The aforementioned limitations of solid dispersions has been done away in the present invention by forming fine crystals/grains/particles of solid dispersion of the drug(s) directly into tablets in a manner similar to that adopted for cube sugar production. Solid dispersions of drugs in carriers of poor compressibility can be easily formed into tablets of any suitable shape/size by any suitable techniques including those known for cube sugar production. Resulting tablets will not only be readily dispersible owing to capillary action but also ensure rapid dissolution of poorly soluble drug because of solid dispersion. Grains of solid dispersion, crystalline as well as amorphous, in any suitable size range(s) can be employed for formation into tablets. Surfactant can also be incorporated in the solid dispersion for further enhancement of dissolution rate. . Suitable drug substance have been exemplified from a variety of known classes of drugs, but are not necessarily limited to, analgesics, anti-inflammatory agents, anthelmintics, anti-arrhythmic agents, antibiotics, anticoagulants, antidepressent, antidiabetic agent, antiepileptic, antihistamines, antihypertensive agents, antimuscarinic agents, antimyobacterial agents, antineoplastic agents, immunosuppressants, antithyroid agents, antiviral agents, anxiolytic sedatives (hypnotics and neuroleptics), beta-adrenoceptor blocking agents, cardiac inotropic agents, contrase media, corticosteroids, cough supressents (expectorants and mucolytics), diagnostics agents, diagnostics imaging agents, diuretics, dopaminergics (antiparkinsonian agents), haemostatics, immunological agents, lipid regulating agents, muscle relaxants, parasympathomimetics, parathyroid calcitonin and biphosphates, prostaglandines, radio-pharmaceuticals, sex harmons ( including steroids), anti-allergic agents, stimulants and anoretics, sympathomimetics, thyroid agents, vasodilator, and xanthines. Preferred drug substance includes those intended for oral administration. Suitable carrier are diverse in nature, which can also be optionally incorporated along with the drug(s) in the solid dispersion are exemplified but not limited by Sugars (e.g. Dextrose, Sucrose, Galactose, Sorbitol, maltose, Xylitol, Mannitol, Lactose, Fructose, etc,) Acids (e.g. Citric acid, Succinic acid, etc), Polymeric materials(e.g. Povidone (PVP), Polyethyleneglycol (PEG), Hydroxypropyl-methyl cellulose (HPMC), Methyl cellulose (MC), Hydroxyethyl cellulose (HEC), Cyclodextrin (CD), Hydroxypropyl cellulose (HPC), Pectin, Galactomannan, Dextrins, Sodium alginate, Gelatin, Carregeenan, Sodium carboxymethyl cellulose, Polyvinyl alcohal (PVA), Gum arabic, Tragacanth, and Guar gum. etc.), Insoluble or enteric Polymer (e.g. Hydroxypropylmethyl cellulose phthalate (HPMCP), Eudragit L-100, Eudragit S-100, Eudragit RL, Eudragit RS, Polymethylacrylate or PolyDL-Aspartic acid, Spheron P40, etc.), Surfactants/ wetting agents (e.g. Polyoxyethylene stearate, Ranex, Poloxamer 188 or Pluronic F 68, Poloxamer 407, Texafor AIP, Deoxycholic acid, Tweens, Spans, Myrj 52, Myrj 51, Myrj59, or Polyoxyethylene 40 Stearate (P40S), Brij 35 etc), Miscellaneous (e.g. Pentaerythritol, Pentaerythrityltetraacetate, Urea, Urethane, Hydroxyalkyl-Xanthines, Dehydroxypropyltheophylline, Nicotinamide, Hydroquinone, Ascorbic acid, Acetamide, Nicotinic acid, Succinamide, etc.), and Combination of Carrier (e.g. Citric acid-Succinic acid, Sugar mixture, Sugars-PEG, Sterol-Surfactants, etc.) etc. and/ or suitable mixture of thereof. Suitable surfactants, which can also be optionally incorporated along with the drug(s) in the solid dispersion are exemplified but not limited by non-ionic, ionic, anionic or amphoteric surfactants. Examples of suitable surfactants include lecithin (phosphatides), gum acacia, cholesterol, tragacanth, stearic acid, benzalkonium chloride, calcium stearate, glycerol monostearate, cetostearyl alcohol, cetomacrogol emulsifying wax, sorbitan esters, polyoxyethylene alkyl ethers (e.g. macrogol ethers such as cetomacrogol 1000), polyoxyethlylene castor oil derivatives, polyoxyethylene sorbitan fatty acid esters ( e.g. Tween), polyethylene glycols, polyoxyethylene stearates, phosphates, sodium dodecylsulfate, carboxymethylcellulose calcium, carboxymethylcellulose sodium, methylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose phthalate, noncrystalline cellulose, magnesium aluminium silicate, triethanolamine, polyvinyl alcohol, polyvinylpyrrolidone, tyloxapol and pluronic or poloxamer etc. Suitable colorants which can also be optionally incorporated along with the drug(s) in the solid dispersion are exemplified but not limited by brilliant blue FCF, indigotin, alphazurine FG, indanthrene blue, fast green FCF, alizarin cyanine, green F, quinizarine green SS, pyranine concentrated, orange II, dibromofluorescein, diiodofluorescein, erythyosin yellowish Na, erythrosine, ponceau SX, lithol rubin B, lithol rubin B Ca, toney red, tetrabromofluorescein, eosine, tetrachlorotetrabromofluorescein, phloxine B, helindone pink CN, acid fuchsine, flaming red, alba red, allura red AC, alizurol purple SS, tertrazine, sunset yellow FCF, fluorescein, naphthol yellow S, uranine, quinoline yellow WS, quinoline yellow SS etc. Suitable sweeteners, which can also be optionally incorporated along with the drug(s) in the solid dispersion are exemplified but not limited by both natural and artificial. Examples of suitable sweeteners include aspartame, cyclamates, glycyrrhizin, saccharins, dextrose, fructose, lactose, maltose, mannitol, sorbitol, sucrose etc. Suitable flavors, which can also be optionally incorporated along with the drug(s) in the solid dispersion are exemplified but not limited by both natural and artificial. Examples of suitable flavors include chocolate, mint (peppermint, spearmint), mint anise, orange, vanillin, Bavarian cream, butterscotch, cherry cream punch, anise birch, black currant, rum peach, spice vanilla, wild cherry, clove, honey-lemon, menthol-eucalyptus, fresh pineapple, grape, passion fruit, raspberry, strawberry, almond, blueberry, toasted nut, anis oil, cardamom oil, caraway, fennel oil, ginger, honey, nutmeg oil, orange oil, rose water etc. The process is illustrated but not limited by the following example Example: A 100 gm mixture of 5 % by weight of famotidine and 95 % by weight of xylitol was blended thoroughly using a glass pestle and mortar and transferred to a beaker. The drug-carrier physical mixtures were heated carefully to about 110°C with constant stirring until clear homogenous melts (dispersion) were obtained. The melt was allow to solidify in a desiccator. The solid mass was then pulverized. Resulting grains passing through # 30 and retain by # 44 were exposed to steam for 5- 8 second and molded in tablets which were removed from molds and dried. We claim: 1. A method for preparing an improved pharmaceutical product, said method comprising the steps of: dispersing a drug(s) along with an additive(s) in a carrier or a mixture of two or more carriers to obtain a solid dispersion; subjecting said solid dispersion to size reduction or agglomeration to obtain said solid dispersion in either discrete or agglomerated form of crystals/particles/grains; and cementing said crystals/particles/grains form by cube sugar technology to get said improved pharmaceutical product. 2. The method of claim 1, wherein said solid dispersion of said drug(s) is obtained through a process selected from a group comprising of melting, hot melt extrusion, co-solvency, spray drying, spray congealing, critical fluid technology and solvent-fusion. 3. A product made by a method as claimed in claim 1, wherein said product comprises said solid dispersion of said drug(s) in said carrier(s), further wherein said solid dispersion of said drug(s) has an arrangement as that of a sugar cube. 4. The product of claim 3, wherein said product further comprises of additives, wherein said additives comprise of a colorant(s) and a sweetener(s). 5. The product of claim 4, wherein said colorant(s) is selected from a group comprising of brilliant blue FCF, indigotin, alphazurine FG, indanthrene blue, fast green FCF, alizarin cyanine, green F, quinizarine green SS, pyranine concentrated, orange II, dibromofluorescein, diiodofluorescein, erythyosin yellowish Na, erythrosine, ponceau SX, lithol rubin B, lithol rubin B Ca, toney red, tetrabromofluorescein, eosine, tetrachlorotetrabromofluorescein, phloxine B, helindone pink CN, acid fuchsine, flaming red, alba red, allura red AC, alizurol purple SS, tertrazine, sunset yellow FCF, fluorescein, naphthol yellow S, uranine, quinoline yellow WS and quinoline yellow SS. 6. The product of claim 4, wherein said sweetener(s) is selected from a group comprising of aspartame, cyclamates, glycyrrhizin, saccharins, dextrose, fructose, lactose, maltose, mannitol, sorbitol and sucrose. 7. The product of claim 3, wherein said product optionally comprises of a surfactant(s). 8. The product of claim 7, wherein said surfactant(s) is selected from a group comprising of non ionic, anionic, cationic and amphoteric surfactants. 9. The product of claim 3, wherein said product optionally comprises of a flavoring agent(s), wherein said flavoring agent(s) is either incorporated in said solid dispersion or sprayed in a solution form onto said solid dispersion of said drug or onto said product after its formation. 10. The product of claim 9, wherein said flavoring agent(s) is selected from a group comprising chocolate, mint (peppermint, spearmint), mint anise, orange, vanillin, Bavarian cream, butterscotch, cherry cream punch, anise birch, black currant, rum peach, spice vanilla, wild cherry, clove, honey-lemon, menthol-eucalyptus, fresh pineapple, grape, passion fruit, raspberry, strawberry, almond, blueberry, toasted nut, anis oil, cardamom oil, caraway, fennel oil, ginger, honey, nutmeg oil, orange oil, and rose water. 11. The product of claim 4, wherein said drug(s) is dispersed along with said additives in said carrier or a mixture of carriers. 12. The product of claim 3, wherein said carrier(s) is selected from a group comprising of sugars, acids, polymeric materials or a mixture thereof. 13. The product of claim 3, wherein said drug(s) is selected from a group comprising of analgesics, anti-inflammatory agents, anthelmintics, anti-arrhythmic agents, antibiotics, anticoagulants, antidepressants, antidiabetic agent, antiepileptic, antihistamines, antihypertensive agents, antimuscarinic agents, antimycobacterial agents, antineoplastic agents, immunosuppressants, antithyroid agents, antiviral agents, anxiolytic sedatives (hypnotics and neuroleptics), beta-adrenoceptor blocking agents, cardiac inotropic agents, contrase media, corticosteroids, cough suppressants (expectorants and mucolytics), diagnostics agents, diagnostics imaging agents, diuretics, dopaminergics (antiparkinsonian agents), haemostatics, immunological agents, lipid regulating agents, muscle relaxants, parasympathomimetics, parathyroid calcitonin and biphosphates, prostaglandines, radio-pharmaceuticals, sex hormones (including steroids), anti-allergic agents, stimulants and anoretics, sympathomimetics, thyroid agents, vasodilator, xanthines. 14. The product of claim 3, wherein said product is a tablet of a suitable size shape.

Full Text

FIELD OF INVENTION
Present invention relates to a process and pharmaceutical products, preferably tablets, made from said process for enhancement of dissolution rate of sparingly soluble drugs leading to their increased bioavailability. Known phenomena/techniques of solid dispersion, capillary action, optional surfactant and optional size reduction have been simultaneously exploited for enhancement of dissolution rate leading to improved bioavailabilty. The tablets made from the process of the present invention also exhibit improved content uniformity.
BACKGROUND OF INVENTION
Dissolution rate of drug plays a prime role in controlling the absorption of the drug from the dosage form. When a drug is administered orally in solid dosage form (such as tablets or capsules), it is designed to undergo series of predetermined stages. The first step towards the absorption process is the disintegration of the dosage form. The second and in fact the slowest or rate-limiting step is found to be dissolution of drug in the fluid at the absorption site. When dissolution is the controlling step in the overall process, absorption is said to be dissolution rate limited. Since the rate-limiting step in the absorption process is dissolution step, therefore, any factor influencing the rate of dissolution must also influence the rate of absorption. According to dissolution theory, two important parameters determining the dissolution rate are the solubility of the drug in the dissolution medium and the surface area of the drug exposed to the medium.
The fact that more than 40 % of newly discovered drugs have little or no water solubility presents a serious challenge to the successful development and commercialization of new drugs in the pharmaceutical industry. No matter how active or potentially active a new molecular entity (NME) is against a particular molecular target, if the NME is not available in solution at the site of action, it is not a viable developmental candidate. As a result, the development of many exciting NMEs stopped before their potential was realized or confirmed because pharmaceutical companies cannot afford to conduct rigorous preclinical and clinical studies on a molecule that does not have a sufficient phamacokinetic profile due to poor water solubility.

Though numerous techniques of diverse nature such as size reduction, complexation, reduction of hydrophobicity, polymorphic and crystal form, salt formation, adsorption, solid dispersion and freeze-drying have been developed for enhancement of dissolution rate but with limited success. Hence improvement of dissolution rate of sparingly soluble drugs still remains a challenge for scientific community.
Solid dispersion is a well known approach for improvement of the dissolution rate and bioavailability of drugs that are poorly water-soluble. It is a dispersion of one or more active ingredients at molecular to microcrystalline level in an inert carrier or matrix at solid state. The carriers used have been physiologically inert compounds that are readily water soluble or water insoluble for fast or controlled dissolution respectively. To achieve faster dissolution rate of poorly water-soluble drug, the drug is dispersed at molecular level in a rapidly water soluble inert carrier to form a solid dispersion. Successful dispersion of the drug in the carrier at molecular level leads to formation of homogeneous phase of the solid dispersion. When such a product comes in contact with gastric fluid, then the water soluble carrier rapidly dissolves resulting in immediate release of the drug at the desired molecular level to cause dissolution with consequent improvement of bioavailability.
Solid dispersions have been extensively studied for improvement of dissolution rate and numerous techniques of diverse nature have been developed for preparation of the same. These include hot melt extrusion, solvent method, fusion, supercritical fluid process, solvent-melting method and spray congealing. Solid dispersions offer numerous advantages as per the following:
* Presence of the drug at molecular level to microcrystalline level in the carrier.
* Rapid dissolution rate.
* Transformation of low dose liquid drug into a solid form.
* Minimization of polymorphic changes and thereby bioavailability problems
* Excellent content uniformity.
* Possibilities to controlled or sustain release by the use of low solubility carriers.
In spite of numerous advantages and extensive work very few products based upon solid dispersions have been successfully commercialized. Major limitations for use of

solid dispersions in the tablet form are attributable to poor compressibility of the carriers and scale up of the manufacturing process. Encapsulation of the solid dispersions in the hard gelatin capsules, on the other hand, delays the dissolution process of the drug because dissolution process will not start till the capsule shell has disintegrated to allow solid dispersion to come in contact with the gastric fluid. Moreover, gelatin capsule shells are susceptible to denaturation.
Novel improved tablets have been conceptualized in the present invention for overcoming of aforementioned limitations of solid dispersions simply by forming fine crystals/grains/particles of solid dispersion of the drug(s) directly into tablets in a manner similar to that adopted for cube sugar production. Solid dispersions of drugs in carriers of poor compressibility can be easily formed into tablets of any suitable shape/size by known cube sugar technology. Resulting tablets will not only be readily dispersible owing to capillary action but also ensure rapid dissolution of poorly soluble drug because of solid dispersion. Surfactant can also be incorporated in the solid dispersion for further enhancement of dissolution rate. Simultaneous exploitation of well-known approaches- solid dispersion, capillary action, optional surfactant and optional particle size reduction will obviously result in steep enhancement of dissolution rate without compromising with content uniformity.
SUMMARY OF THE INVENTION
The object of present invention is to provide a process and pharmaceutical products, preferably tablets, made from said process for enhancement of dissolution rate of sparingly soluble drugs leading to their increased bioavailability. Simultaneous exploitation of well-known approaches- solid dispersion, capillary action, optional surfactant and optional size reduction in the proposed technique will obviously result in steep enhancement of dissolution rate without compromising with content uniformity.
DISCLOSURE OF THE INVENTION
The aforementioned limitations of solid dispersions has been done away in the present invention by forming fine crystals/grains/particles of solid dispersion of the drug(s)

directly into tablets in a manner similar to that adopted for cube sugar production. Solid dispersions of drugs in carriers of poor compressibility can be easily formed into tablets of any suitable shape/size by any suitable techniques including those known for cube sugar production. Resulting tablets will not only be readily dispersible owing to capillary action but also ensure rapid dissolution of poorly soluble drug because of solid dispersion. Grains of solid dispersion, crystalline as well as amorphous, in any suitable size range(s) can be employed for formation into tablets. Surfactant can also be incorporated in the solid dispersion for further enhancement of dissolution rate. .
Suitable drug substance have been exemplified from a variety of known classes of drugs, but are not necessarily limited to, analgesics, anti-inflammatory agents, anthelmintics, anti-arrhythmic agents, antibiotics, anticoagulants, antidepressent, antidiabetic agent, antiepileptic, antihistamines, antihypertensive agents, antimuscarinic agents, antimyobacterial agents, antineoplastic agents, immunosuppressants, antithyroid agents, antiviral agents, anxiolytic sedatives (hypnotics and neuroleptics), beta-adrenoceptor blocking agents, cardiac inotropic agents, contrase media, corticosteroids, cough supressents (expectorants and mucolytics), diagnostics agents, diagnostics imaging agents, diuretics, dopaminergics (antiparkinsonian agents), haemostatics, immunological agents, lipid regulating agents, muscle relaxants, parasympathomimetics, parathyroid calcitonin and biphosphates, prostaglandines, radio-pharmaceuticals, sex harmons ( including steroids), anti-allergic agents, stimulants and anoretics, sympathomimetics, thyroid agents, vasodilator, and xanthines. Preferred drug substance includes those intended for oral administration.
Suitable carrier are diverse in nature, which can also be optionally incorporated along with the drug(s) in the solid dispersion are exemplified but not limited by Sugars (e.g. Dextrose, Sucrose, Galactose, Sorbitol, maltose, Xylitol, Mannitol, Lactose, Fructose, etc,) Acids (e.g. Citric acid, Succinic acid, etc), Polymeric materials(e.g. Povidone (PVP), Polyethyleneglycol (PEG), Hydroxypropyl-methyl cellulose (HPMC), Methyl cellulose (MC), Hydroxyethyl cellulose (HEC), Cyclodextrin (CD), Hydroxypropyl cellulose (HPC), Pectin, Galactomannan, Dextrins, Sodium alginate, Gelatin, Carregeenan, Sodium carboxymethyl cellulose, Polyvinyl alcohal (PVA), Gum arabic, Tragacanth, and Guar gum. etc.), Insoluble or enteric Polymer (e.g. Hydroxypropylmethyl cellulose

phthalate (HPMCP), Eudragit L-100, Eudragit S-100, Eudragit RL, Eudragit RS, Polymethylacrylate or PolyDL-Aspartic acid, Spheron P40, etc.), Surfactants/ wetting agents (e.g. Polyoxyethylene stearate, Ranex, Poloxamer 188 or Pluronic F 68, Poloxamer 407, Texafor AIP, Deoxycholic acid, Tweens, Spans, Myrj 52, Myrj 51, Myrj59, or Polyoxyethylene 40 Stearate (P40S), Brij 35 etc), Miscellaneous (e.g. Pentaerythritol, Pentaerythrityltetraacetate, Urea, Urethane, Hydroxyalkyl-Xanthines, Dehydroxypropyltheophylline, Nicotinamide, Hydroquinone, Ascorbic acid, Acetamide, Nicotinic acid, Succinamide, etc.), and Combination of Carrier (e.g. Citric acid-Succinic acid, Sugar mixture, Sugars-PEG, Sterol-Surfactants, etc.) etc. and/ or suitable mixture of thereof.
Suitable surfactants, which can also be optionally incorporated along with the drug(s) in
the solid dispersion are exemplified but not limited by non-ionic, ionic, anionic or
amphoteric surfactants. Examples of suitable surfactants include lecithin (phosphatides),
gum acacia, cholesterol, tragacanth, stearic acid, benzalkonium chloride, calcium
stearate, glycerol monostearate, cetostearyl alcohol, cetomacrogol emulsifying wax,
sorbitan esters, polyoxyethylene alkyl ethers (e.g. macrogol ethers such as cetomacrogol
1000), polyoxyethlylene castor oil derivatives, polyoxyethylene sorbitan fatty acid esters
( e.g. Tween), polyethylene glycols, polyoxyethylene stearates, phosphates, sodium
dodecylsulfate, carboxymethylcellulose calcium, carboxymethylcellulose sodium,
methylcellulose, hydroxyethylcellulose, hydroxypropylcellulose,
hydroxypropylmethylcellulose phthalate, noncrystalline cellulose, magnesium aluminium silicate, triethanolamine, polyvinyl alcohol, polyvinylpyrrolidone, tyloxapol and pluronic or poloxamer etc.
Suitable colorants which can also be optionally incorporated along with the drug(s) in the solid dispersion are exemplified but not limited by brilliant blue FCF, indigotin, alphazurine FG, indanthrene blue, fast green FCF, alizarin cyanine, green F, quinizarine green SS, pyranine concentrated, orange II, dibromofluorescein, diiodofluorescein, erythyosin yellowish Na, erythrosine, ponceau SX, lithol rubin B, lithol rubin B Ca, toney red, tetrabromofluorescein, eosine, tetrachlorotetrabromofluorescein, phloxine B, helindone pink CN, acid fuchsine, flaming red, alba red, allura red AC, alizurol purple

SS, tertrazine, sunset yellow FCF, fluorescein, naphthol yellow S, uranine, quinoline yellow WS, quinoline yellow SS etc.
Suitable sweeteners, which can also be optionally incorporated along with the drug(s) in the solid dispersion are exemplified but not limited by both natural and artificial. Examples of suitable sweeteners include aspartame, cyclamates, glycyrrhizin, saccharins, dextrose, fructose, lactose, maltose, mannitol, sorbitol, sucrose etc. Suitable flavors, which can also be optionally incorporated along with the drug(s) in the solid dispersion are exemplified but not limited by both natural and artificial. Examples of suitable flavors include chocolate, mint (peppermint, spearmint), mint anise, orange, vanillin, Bavarian cream, butterscotch, cherry cream punch, anise birch, black currant, rum peach, spice vanilla, wild cherry, clove, honey-lemon, menthol-eucalyptus, fresh pineapple, grape, passion fruit, raspberry, strawberry, almond, blueberry, toasted nut, anis oil, cardamom oil, caraway, fennel oil, ginger, honey, nutmeg oil, orange oil, rose water etc.
The process is illustrated but not limited by the following example Example: A 100 gm mixture of 5 % by weight of famotidine and 95 % by weight of xylitol was blended thoroughly using a glass pestle and mortar and transferred to a beaker. The drug-carrier physical mixtures were heated carefully to about 110°C with constant stirring until clear homogenous melts (dispersion) were obtained. The melt was allow to solidify in a desiccator. The solid mass was then pulverized. Resulting grains passing through # 30 and retain by # 44 were exposed to steam for 5- 8 second and molded in tablets which were removed from molds and dried.

We claim:
1. A method for preparing an improved pharmaceutical product, said method
comprising the steps of:
dispersing a drug(s) along with an additive(s) in a carrier or a mixture of two
or more carriers to obtain a solid dispersion;
subjecting said solid dispersion to size reduction or agglomeration to obtain
said solid dispersion in either discrete or agglomerated form of
crystals/particles/grains; and
cementing said crystals/particles/grains form by cube sugar technology to get
said improved pharmaceutical product.
2. The method of claim 1, wherein said solid dispersion of said drug(s) is obtained through a process selected from a group comprising of melting, hot melt extrusion, co-solvency, spray drying, spray congealing, critical fluid technology and solvent-fusion.
3. A product made by a method as claimed in claim 1, wherein said product comprises said solid dispersion of said drug(s) in said carrier(s), further wherein said solid dispersion of said drug(s) has an arrangement as that of a sugar cube.
4. The product of claim 3, wherein said product further comprises of additives, wherein said additives comprise of a colorant(s) and a sweetener(s).
5. The product of claim 4, wherein said colorant(s) is selected from a group comprising of brilliant blue FCF, indigotin, alphazurine FG, indanthrene blue, fast green FCF, alizarin cyanine, green F, quinizarine green SS, pyranine concentrated, orange II, dibromofluorescein, diiodofluorescein, erythyosin yellowish Na, erythrosine, ponceau SX, lithol rubin B, lithol rubin B Ca, toney red, tetrabromofluorescein, eosine, tetrachlorotetrabromofluorescein, phloxine B, helindone pink CN, acid fuchsine, flaming red, alba red, allura red AC, alizurol purple SS, tertrazine, sunset yellow FCF, fluorescein, naphthol yellow S, uranine, quinoline yellow WS and quinoline yellow SS.
6. The product of claim 4, wherein said sweetener(s) is selected from a group comprising of aspartame, cyclamates, glycyrrhizin, saccharins, dextrose, fructose, lactose, maltose, mannitol, sorbitol and sucrose.

7. The product of claim 3, wherein said product optionally comprises of a surfactant(s).
8. The product of claim 7, wherein said surfactant(s) is selected from a group comprising of non ionic, anionic, cationic and amphoteric surfactants.
9. The product of claim 3, wherein said product optionally comprises of a flavoring agent(s), wherein said flavoring agent(s) is either incorporated in said solid dispersion or sprayed in a solution form onto said solid dispersion of said drug or onto said product after its formation.
10. The product of claim 9, wherein said flavoring agent(s) is selected from a group comprising chocolate, mint (peppermint, spearmint), mint anise, orange, vanillin, Bavarian cream, butterscotch, cherry cream punch, anise birch, black currant, rum peach, spice vanilla, wild cherry, clove, honey-lemon, menthol-eucalyptus, fresh pineapple, grape, passion fruit, raspberry, strawberry, almond, blueberry, toasted nut, anis oil, cardamom oil, caraway, fennel oil, ginger, honey, nutmeg oil, orange oil, and rose water.
11. The product of claim 4, wherein said drug(s) is dispersed along with said additives in said carrier or a mixture of carriers.
12. The product of claim 3, wherein said carrier(s) is selected from a group comprising of sugars, acids, polymeric materials or a mixture thereof.
13. The product of claim 3, wherein said drug(s) is selected from a group comprising of analgesics, anti-inflammatory agents, anthelmintics, anti-arrhythmic agents, antibiotics, anticoagulants, antidepressants, antidiabetic agent, antiepileptic, antihistamines, antihypertensive agents, antimuscarinic agents, antimycobacterial agents, antineoplastic agents, immunosuppressants, antithyroid agents, antiviral agents, anxiolytic sedatives (hypnotics and neuroleptics), beta-adrenoceptor blocking agents, cardiac inotropic agents, contrase media, corticosteroids, cough suppressants (expectorants and mucolytics), diagnostics agents, diagnostics imaging agents, diuretics, dopaminergics (antiparkinsonian agents), haemostatics, immunological agents, lipid regulating agents, muscle relaxants, parasympathomimetics, parathyroid calcitonin and biphosphates, prostaglandines, radio-pharmaceuticals, sex hormones (including steroids), anti-allergic agents,

stimulants and anoretics, sympathomimetics, thyroid agents, vasodilator, xanthines.
14. The product of claim 3, wherein said product is a tablet of a suitable size shape.

Documents:

2695-del-2005-Abstract-(08-03-2010).pdf

2695-DEL-2005-Abstract-(15-02-2010).pdf

2695-DEL-2005-Abstract-(25-03-2010).pdf

2695-del-2005-abstract.pdf

2695-del-2005-Claims-(08-03-2010).pdf

2695-DEL-2005-Claims-(15-02-2010).pdf

2695-DEL-2005-Claims-(25-03-2010).pdf

2695-del-2005-claims.pdf

2695-DEL-2005-Correspondence-Others (15-02-2010).pdf

2695-del-2005-Correspondence-Others- (08-03-2010).pdf

2695-del-2005-Correspondence-Others-(08-03-2010).pdf

2695-DEL-2005-Correspondence-Others-(25-03-2010).pdf

2695-del-2005-correspondence-others.pdf

2695-del-2005-Description (Complete)-(08-03-2010).pdf

2695-DEL-2005-Description (Complete)-(15-02-2010).pdf

2695-DEL-2005-Description (Complete)-(25-03-2010).pdf

2695-del-2005-description (complete).pdf

2695-DEL-2005-Form-1-(25-03-2010).pdf

2695-del-2005-form-1.pdf

2695-del-2005-Form-18-(08-03-2010).pdf

2695-del-2005-Form-2-(08-03-2010).pdf

2695-DEL-2005-Form-2-(15-02-2010).pdf

2695-DEL-2005-Form-2-(25-03-2010).pdf

2695-del-2005-form-2.pdf

2695-del-2005-Form-26-(08-03-2010).pdf

2695-DEL-2005-Form-26-(15-02-2010).pdf

2695-del-2005-Form-3-(08-03-2010).pdf

2695-DEL-2005-Form-3-(15-02-2010).pdf

2695-DEL-2005-GPA-(15-02-2010).pdf

2695-DEL-2005-Petition 137-(15-02-2010).pdf

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Patent Number

240034

Indian Patent Application Number

2695/DEL/2005

PG Journal Number

30/04/2010

Publication Date

30-Apr-2010

Grant Date

23-Apr-2010

Date of Filing

07-Oct-2005

Name of Patentee

MADAN, DR. ANIL KUMAR

Applicant Address

FACULTY OF PHARMACEUTICAL SCIENCES, MAHARSHI DAYANAND UNIVERSITY, ROHTAK, HARYANA, INDIA 124001

Inventors:

#	Inventor's Name	Inventor's Address
1	GUPTA, VISHAL	FACULTY OF PHARMACEUTICAL SCIENCES, MAHARSHI DAYANAND UNIVERSITY, ROHTAK, HARYANA, INDA- 124001
2	MADAN, DR. ANIL KUMAR	FACULTY OF PHARMACEUTICAL SCIENCES, MAHARSHI DAYANAND UNIVERSITY, ROHTAK, HARYANA, INDIA 124001

PCT International Classification Number

A61K 9/10

PCT International Application Number

N/A

PCT International Filing date

PCT Conventions:

#	PCT Application Number	Date of Convention	Priority Country
1			NA