Title of Invention	STABLE STATIN COMPOSITIONS
Abstract	A stable pharmaceutical composition used for the treatment of hyperlipidemia and/or hypercholesterolemia, comprising at least one statin and an eddective amount of glycine.

Full Text

FORM-2 THE PATENTS ACT, 1970 (39 OF 1970) The Patent Rules, 2003 PROVISIONAL SPECIFICATION (See Section 10 and Rule 13) "STABLE STATIN COMPOSITIONS" Inventia Healthcare Private Limited having its administrative office at Unit No. S - 4 , Khira Industrial Estate, B.M Bhargava Road, Santacruz West, Mumbai 400054, Maharashtra, India an Indian Company The following specification describes the invention. Field of the Invention: The present invention relates to stable oral pharmaceutical compositions comprising statin and process for preparation thereof. Background of the Invention: It is well known that statins such as lovastatin, simvastatin, rosuvastatin, visastatin, atorvastatin, pravastatin, mevastatin, fluvastatin, rivastatin, cervastatin, pitavastatin nisvastatin, itavastatin, derivatives and analogs thereof are HMG-CoA reductase inhibitors used in the treatment of hyperlipidemia and /or hypercholesterolemia. However, these statins are unstable in acidic environment in which hydroxy acids moiety of statin undergoes degradation into a lactone. In addition to its susceptibility to low pH environment, these statins are also susceptible to heat, moisture and light. It undergoes rapid decomposition when exposed to UV or fluorescent light. Apart from the above mentioned environmental factors, excipients used in the pharmaceutical composition may also accelerate the degradation of statin. Therefore, these stains should not only be protected from the environmental factors but also should be protected from the potential excipients that cause degradation. By ensuring sufficient protection to statin, impurities in the compositions can be minimized, thereby reducing the side effects associated with such impurities, resulting in the improvement in the quality of treatment. U.S. Patent 5,686,104 and U.S. Patent 6,126,971 disclose stable oral pharmaceutical composition comprising atorvastatin in which the formulation is stabilized using alkaline earth metal salts in particular calcium carbonate in an amount from about 5% to about 75% by weight of the composition. U.S. Patent Application 2004/0247673 discloses a wet granulated pharmaceutical composition comprising atorvastatin or pharmaceutical ? salt thereof with less than about 5 weight % of an alkaline earth metal salt additive with a disintegrant which provides atorvastatin with not more than about 3% atorvastatin lactone based on the ratio of lactone peak area compared to the total drug-related peak integrated areas. U.S. Patent Application 20Q4/0253305 discloses a dry granulated pharmaceutical composition comprising atorvastatin or pharmaceutical salt thereof with less than about 5 weight % of an alkaline earth metal salt additive. U.S. Patent Application 2004/0271717 discloses a unit dosage form of atorvastatin or pharmaceutical salt thereof, prepared without a granulation step. The composition contains less than about 5 weight % of an alkaline earth metal salt additive. PCT Publication WO 2006/059224 discloses a solid pharmaceutical composition comprising a solid dispersion of amorphous atorvastatin with a melt-processible polymer and one or more optional pharmaceutical^ acceptable excipients. The said composition further comprises a stabilizer for reducing chemical degradation of amorphous atorvastatin, the said stabilizer being a salt of alkali metal or alkaline earth metal. U.S. Patent 6,680,341 and U.S. Patent Application 20040072894 discloses a stabilized pharmaceutically active substance consisting of a salt of HMG - C oA reductase inhibitor and an alkaline substance or buffering agent wherein the said active substance has a pH in the range of 7 to 11, The stabilized active substance is incorporated in the formulation further comprising a second buffering agent wherein the formulation has a pH betow 9. Typical buffering agent used in \he composition includes sodium or potassium citrate, sodium phosphate, dibasic sodium phosphate, calcium carbonate, hydrogen phosphate, phosphate, sulphate, sodium or magnesium carbonate, sodium ascorbinate, benzoate, sodium or potassium hydrogen carbonate, lauryl sulphate, or mixtures of such buffering agents. U.S. Patent 6,531,507 and U.S. Patent 6,806,290 discloses a composition comprising a homogeneous mixture of a HMG CoA reductase inhibitor with a buffering substance or a basifying substance in a finely distributed form, obtained by co-crystallization and/or co-precipitation of said HMG CoA reductase inhibitor and said buffering substance or basifying substance, which has a HPLC purity of at least 98% or containing less than 0.5% weight of lactone of said HMG CoA reductase inhibitor. The buffering substance or agent is selected from the group consisting of salts of inorganic acids, salts of organic bases or salts of organic acids. The basifying substance or agent is selected from the group consisting of metal oxides, inorganic bases, organic bases and organic acids with basic character. Examples of such agent includes magnesium oxide, aluminum oxide, sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide, succinimide, 1-adamantyl amine, N,N'-bis(2-hydroxyethyl) ethylendiamine, tris (hydroxymethyl) aminomethan, D(-)-N-methylglucamine, 3-(N-morpholino) propanesulfonic acid, 4-(cyclohexyl amino)-1-butansulfonic acid, 4-(cyclohexyl amino) etansulfonic acid and the alkaline metal or alkaline earth metal salts of these acids, arginine, ornithine, lysine, or the like. U.S. Patent Application 2003/0175338 discloses a stabilized formulation comprising amorphous and / or crystalline atorvastatin having improved bioavailability and bioequivalence. The formulation is stabilized by mixing atorvastatin with an alkali metal salt additive at between approximately 1.2% and less than 5% w/w of the formulation. The alkali metal salt additive may be one or more of sodium carbonate, sodium bicarbonate, sodium hydroxide, sodium silicate, disodium hydrogen orthophosphate, 4 sodium dihydrogen phosphate, disodium hydrogen phosphate, sodium phosphate, sodium aluminate, calcium carbonate, calcium hydroxide, magnesium carbonate, magnesium hydroxide, magnesium silicate, magnesium aluminate, and aluminum magnesium hydroxide. PCT Publication WO 2009/010787 discloses a stable composition comprising one or more HMG-COA reductase inhibitors, wherein the composition does not include an alkaline agent. The pH of such composition when dispersed in water is in the range of 7 or lower. U.S. Patent Application 2007/0116758 discloses a pharmaceutical dosage form, which reduces food effect encountered by administration of atorvastatin, comprising: (a) an effective amount of atorvastatin; and (b) a pharmaceutically acceptable excipient, wherein the dosage form exhibits a food effect of less than about 45% as characterized by C.sub.max values, and the atorvastatin contains at least one atorvastatin selected from the group consisting of atorvastatin hemi-calcium Form V, atorvastatin having an average particle size of at most about 50 microns, and micronized atorvastatin. Stabilizing excipient is selected from the group consisting of calcium oxide, magnesium oxide, calcium magnesium carbonate, carbonates or bicarbonates of sodium, potassium or ammonium; ammonium or alkali metal salts of phosphoric acid or pyrophosphate; ammonium or alkali metal salts of carboxylic acids or fatty acids; calcium magnesium acetate, ammonium or alkali metal salts of aspartic or glutamic acid; carbonates of lysine or arginine; bicarbonates of lysine, arginine, cystine or histidine; free base forms of lysine, arginine, tryptophan, histidine, asparagine or glutamine; carboxylic acid salts of lysine, arginine or histidine; salt forms of cystine, phenols, biophenols or flavonoids, vitamin P, tyrosine, isoflavones, polymers carrying amine functions, polymers carrying acid functions in their salt forms, polyvinyl 5 acetate or phthalate; and peptides or proteins with iso-electric point greater than 4.5. PCT Publication WO2005/011737 discloses a stable composition of at least one therapeutic agent susceptible to degradation and at least one casemate salt of aa amino add. as a stabilizing, ag.ent The carbonate salt of the said amino acid is selected from the group consisting of monosodium glycine carbonate, disodium glycine carbonate, magnesium glycine carbonate, lithium glycine carbonate, calcium glycine carbonate, arginine carbonate and lysine carbonate. U.S. Patent Application 2008/0038332 discloses a stabilized pharmaceutical formulation comprising an intimate admixture or admixture of atorvastatin calcium, a water-insoluble stabilizing alkaline excipient or a combination of two or more water-insoluble stabilizing alkaline excipients, an antioxidant or a combination of two or more antioxidants, and at least one or more pharmaceutical^ acceptable inert excipients or carriers. The water insoluble stabilizing alkaline excipient is selected from the group consisting of zinc carbonate, zinc dibasic phosphate, zinc tribasic phosphate, cobalt carbonate, cobalt tribasic phosphate, calcium citrate, magnesium citrate, calcium glycerophosphate, magnesium glycerophosphate, sodium glycerophosphate, potassium glycerophosphate, magnesium dibasic phosphate, magnesium tribasic phosphate, magnesium carbonate hydroxide or calcium tribasic phosphate. US Patent 6,558,659 discloses a stabilized pharmaceutical composition for the treatment of dyslipidemia, comprising an active component and a stebfeYTig effective arriowrA trf s\ teat-sA ori© Bm^o-tjTOup roTfiaVnrng polymeric compound or at least one amino-group containing polymeric compound, or combination thereof, wherein said stabilized pharmaceutical 6 composition does not contain a stabilizing effective amount of another stabilizer or a combination of other stabilizers. Stabilizer is selected from the group consisting of polyvinylpyrrolidone, cross-linked polyvinylpyrrolidone, copolymers of vinylpyrrolidone and vinyl acetate, cholestyramine, and polynoxylin. U.S. Patent 6,911,472 discloses a pharmaceutical composition comprising an HMG-CoA reductase inhibitor and an aminosugar. This aminosugar is used as a pH-adjusting (basifying) agent and is able to adjust a pH of said composition in aqueous dispersion to 7 or greater. A preferred aminosugar is N-methylglucamine. U. S. Patent 7,030,151 discloses a pharmaceutical formulation comprising atorvastatin calcium and a pH adjusting substance, wherein the pharmaceutical formulation when dissolved in a liquid aqueous medium increases the pH of said medium to a pH equal to or greater than pK.sub.a+1 of atorvastatin calcium. The pH adjusting substance used in the formulation is selected from the group consisting of metal oxides, inorganic bases, organic bases, oxides or hydroxides of the alkaline or alkaline earth metals, alkaline phosphate buffers, organic amines and salts of organic and inorganic aids. U. S. Patent Application 2007/0190138 discloses a stable pharmaceutical composition for oral administration comprising atorvastatin or a pharmaceutically acceptable salt thereof and an amount of a pharmaceutically acceptable organic alkalizing compound capable of establishing a micro-environment for atorvastatin having a pH of at least about 5. The organic alkalizing compound is selected from the group consisting of ammonia, ammonium lactate, ammonium bicarbonate, ammonium hydroxide, ammonium phosphate dibasic, mono ethanolamine, diethanolamine, triethanolamine, 7 trihydroxymethylaminomethane, ethylenediamine, N-methyl glucamide, 6N-methyl glucamine, meglucamine, L-lysine and 2-amino-2-(hydroxymethyl)-l ,3-propanediol (tromethamine). U. S. Patent Application 2008/0182887 discloses a stable oral pharmaceutical composition comprising atorvastatin or its pharmaceutically acceptable salt and pharmaceutically acceptable carrier comprising about 0.5% to about 3.0% by weight of tromethamine and an additional stabilizer in an amount sufficient to prevent degradation of the atorvastatin or its pharmaceutically acceptable salt and containing atorvastatin lactone less than 0.5% by weight of atorvastatin wherein the amount of atorvastatin lactone remains substantially unchanged upon storage at 40.degree. C. at 75% relative humidity for 3 months in closed container containing a desiccant. The additional stabilizer in the composition is an antioxidant selected from a group comprising, butylated hydroxytoluene, butylated hydroxyanisole, DL-alpha-tocopherol, propyl gallate, octyl gallate, ethylenediamine tetraacetate, ascorbyl palmitate, acetyl cysteine, ascorbic acid, sodium ascorbate, fumaric acid, lecithin and mixtures thereof. U.S. Patent 5,030,447 and U.S. Patent 5,180,589 discloses a pharmaceutical tablet composition which has enhanced stability comprising pravastatin which is sensitive to a low pH environment, one of more fillers, one or more binders, one or more disintegrants, one of more lubricants and one or more basifying agents to impart a desired pH of at least 9 to an aqueous dispersion of said composition. The basifying agent is selected from an alkali metal hydroxide, an alkaline earth metal hydroxide or ammonium hydroxide. PCT Publication WO03097039 discloses a solid composition for oral administration comprising atorvastatin calcium and at least one sodium or 8 potassium compound, such that either an aqueous dispersion of the composition is capable of providing a pH above 11, or alternatively the composition comprises particles which comprise said atorvastatin calcium and said sodium or potassium compound, and an aqueous dispersion of said particles is capable of producing a pH above 11. The said sodium or potassium compound is selected from sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, tribasic sodium phosphate and tribasic potassium phosphate. To obtain stable statin composition, prior art discloses the use of: • alkaline earth metal salts in particular calcium carbonate; or • alkaline substance or buffering agent; or • melt-processible polymer and alkaline metal or alkaline earth metal salt; or • co-crystallization and/or co-precipitation with buffering substance selected from the group consisting of salts of inorganic acids, salts of organic bases or salts of organic acids or basifying substance selected from the group consisting of metal oxides, inorganic bases, organic bases and organic acids with basic character; or • alkali metal salt additive; or • carbonate salt of an amino acid; or • water insoluble alkaline excipient and antioxidant; or • at least one amido or one amino-group containing polymeric compound; or • amino sugar; or • pH adjusting substance used such as metal oxides, inorganic bases, organic bases, oxides or hydroxides of the alkaline or alkaline earth metals, alkaline phosphate buffers, organic amines and salts of organic and inorganic aids; or • organic alkalizing compound; or 9 • mixture of tromethamine and antioxidant; or • alkali metal hydroxide, an alkaline earth metal hydroxide or ammonium hydroxide; or • at least one sodium or potassium compound OBJECTS OF THE INVENTION The main object of the invention is to provide stable oral pharmaceutical compositions comprising statin and glycine as a stabilizer. Another object of the invention is to provide a process for the preparation of such pharmaceutical compositions. DETAILED DESCRIPTION OF THE INVENTION The term, "statin" and "HMG-CoA reductase inhibitors" as used herein, are interchangeably used and includes one or more of lovastatin, simvastatin, rosuvastatin, visastatin, atorvastatin, pravastatin, mevastatin, fluvastatin, rivastatin, cervastatin, pitavastatin nisvastatin, itavastatin, derivatives and analogs thereof including their salts, solvates, hydrates, anhydrates, enantiomers, crystalline form, amorphous form, and equivalents thereof. The pharmaceutical acceptable salt includes but is not limited to sodium, potassium, lithium, calcium, magnesium, aluminum, iron, zinc or amine salts. The present invention provides a stable oral pharmaceutical composition characterized by enhanced stability of at least one statin as active ingredient in the composition. In accordance with the present invention, storage stable pharmaceutical compositions are provided which comprises of statin and a stabilizer, used in the treatment of hyperlipidemia and / or hypercholesterolemia. 10 The stable oral pharmaceutical compositions of the present invention comprises of statin and glycine as a stabilizer. The pharmaceutical composition of the present invention, which is preferably in the form of a tablet or capsule comprises at least one statin or HMG-CoA reductase inhibitor as an active ingredient selected from lovastatin, simvastatin, rosuvastatin, visastatin, atorvastatin, pravastatin, mevastatin, fluvastatin, rivastatin, cervastatin, pitavastatin nisvastatin, itavastatin, their salts, derivatives, and analogs thereof. More specifically, the stable oral pharmaceutical composition of the present invention comprises of statin from about 1% to about 50% by weight, preferably from about 2% to about 20% by weight, more preferably from about 5% to about 10% by weight, most preferably from about 7% to about 8% by weight of the composition. Though, there is no restriction on the particle size range of the statin used, micronized statin having mean particle size [d(0.5VJ less than about 50 microns, or less than about 20 microns, or less than about 10 microns, or less than about 5 microns is preferred. The stable oral pharmaceutical composition of the present invention comprises of stabilizing effective amount of glycine from about 0.1% to 75% by weight, preferably from about 0.5% to about 50% by weight, more preferably from about 0.75% to about 25% by weight, and most preferably from about 1% to about 10% by weight of the composition. In one of the embodiments of the invention, the stabilizing effective amount of glycine is from about 2% to about 5% by weight of the composition. 11 In another embodiment of the invention, the stabilizing effective amount of glycine is from about 3% to about 4% by weight of the composition. The pharmaceutical compositions of the present invention may optionally comprise of one or more pharmaceutically acceptable excipients selected from the group of diluents, binder, disintegrants, antioxidants, lubricants, glidants, and chelating agents. The process for preparing stable oral pharmaceutical compositions comprising statin and glycine as a stabilizer comprises steps of: a) mixing statin, stabilizing additive glycine, and optionally at least one or more pharmaceutically acceptable excipients selected from the group of diluents, binder, disintegrants, antioxidants, lubricants, glidants, and chelating agents to obtain drug mixture; b) the drug mixture so obtained is filled in capsule or is processed further using direct compression, dry granulation, wet granulation or extrusion spheronization technique. In one of the embodiments of the invention, the drug mixture so obtained is compressed into tablets. In another embodiment of the invention, the drug mixture so obtained is further processed that comprises steps of: a) dry granulating the drug mixture by slugging or roll compacting or any other suitable means; b) milling the slugs or compacts to obtain granules of desired size; c) optionally sieving the said granules; d) optionally mixing the said granules with at least one ingredient selected from a stabilizing additive glycine, diluents, binder, disintegrants, antioxidants, lubricants, glidants, chelating agents and mixtures thereof; 12 e) optionally filling the resulting granules in capsules or compressing into tablets. In yet another embodiment of the invention, the drug mixture so obtained is further processed that comprises steps of: a) wet granulating the powder mixture using solvent(s) optionally comprising at least one or more pharmaceutical^ acceptable excipients selected from glycine, binder, antioxidants, and chelating agent under shear to obtain the granules; b) optionally milling or sieving said wet granules; c) drying the said granules; d) optionally milling and/or sieving said dried granules; e) optionally mixing the said granules with at least one or more pharmaceutical^ acceptable excipients selected from glycine, diluents, binder, disintegrants, antioxidants, lubricants, glidants, chelating agents and mixtures thereof; f) optionally filling the resulting granules in capsules or compressing into tablets. In yet another embodiment of the invention, the drug mixture so obtained is further processed that comprises steps of: a) wet granulating the powder mixture using solvent(s) optionally comprising at least one or more pharmaceutical^ acceptable excipients selected from glycine, binder, antioxidants, and chelating agent under shear to obtain the granules; b) extruding and spheronizing said granules to obtain pellets; c) drying the said pellets; d) optionally mixing the said pellets with at least one or more pharmaceutical^ acceptable excipients selected from glycine, diluents, binder, disintegrants, antioxidants, lubricants, glidants, chelating agents and mixtures thereof; 13 e) optionally filling the resulting pellets in capsules or compressing into tablets. In a preferred embodiment of the invention, a method for the preparation of the pharmaceutical compositions comprising statin comprises sequential steps of: a) mixing at least one statin with a stabilizing additive glycine, and optionally at least one or more pharmaceutically acceptable excipients selected from the group of diluents, binders, disintegrants, to obtain drug admixture; b) wet granulating the powder mixture using a solvent comprising at least one antioxidant, c) adding sufficient solvent to step b) under shear to obtain the granules; d) drying the said granules; e) milling and/or sieving said dried granules; f) mixing the said granules with at least one ingredient selected form disintegrants, lubricants, glidants, and mixtures thereof; g) compressing the resulting granules into tablets. The pharmaceutical composition in the form of granules, pellets or tablets may optionally be film coated with a film coating material by the process known to a person skilled in the art. The solvent used in granulation and film coating is selected from aqueous, alcoholic, hydro-alcoholic, and organic solvents. Preferably, the solvent is selected from water, methanol, ethanol, isopropanol, acetone, dichloromethane, and mixtures thereof. The diluents may be selected from amongst one or more of those diluents known in the art. Such diluent is preferably selected from the group of 14 carbohydrates, microcrystalline cellulose, silicified microcrystalline, cellulose, powdered cellulose, microfine cellulose, corn starch, modified starch, pregelatinized starch, starch 1500, dextrin, dextran, maltodextrin, calcium phosphate, dibasic calcium phosphate, tribasic calcium phosphate, calcium sulfate, carboxymethylcellulose (CMC), sodium CMC, potassium CMC, calcium CMC; cetyl alcohol, stearyl alcohol, waxes, cyclodextrins, and mixtures thereof. A carbohydrate is selected from glucose, lactose, mannitol, sucrose, dextrose, sorbitol, fructose, sorbitol, compressible sugar, and mixtures thereof. The diluent may be present from about 1% to 95% by weight of the composition. Binder is selected from the group of cellulose derivatives such as hydroxypropylmethylcellulose (HPMC), hydroxypropylcellulose (HPC), ethylcellulose, carboxymethylcellulose sodium, methylcellulose, hydroxyethylcellulose, microcrystalline cellulose, polymethacrylates, sugars such as lactose, sucrose etc.; polyvinylpyrrolidone (PVP), vinyl pyrrolidone-vinyl acetate copolymer, polyvinyl alcohol, gelatin, waxes, fatty alcohols such as stearyl alcohol, cetyl alcohol; gelatin, starch, pregelatinized starch, carbomer, gums like xanthan gum, guar gum, acacia, locust bean gum, alginates and mixtures thereof. Polymethacrylates such as Eudragit RTM RL30D, Eudragit RTM RLPO, Eudragit RTM RL, Eudragit RTM RS30D, Eudragit RTM RSPO, Eudragit RTM RS, Eudragit RTM NE30D, Eudragit RTM NE40D, Eudragit RTM NM30D and Eudragit RTM E are used. The binder is preferably selected from HPMC, HPC, PVP, microcrystalline cellulose, lactose and mixtures thereof. The binder may be present from about 0.1% to 50% by weight of the composition. Disintegrant is selected from the group of sodium starch glycolate, crospovidone, croscarmellose sodium, croscarmellose calcium, croscarmellose potassium, crosslinked carboxymethyl starch, starch, 15 modified starch, pregelatinized starch, starch 1500, microcrystalline cellulose, hydroxypropylcellulose, sodium carboxymethylcellulose, and mixtures thereof. Disintegrant is up to 75%, preferably from 1 to 50%, more preferably from 2.5 to 25% and most preferably from 5 to 15% by weight of the composition. Lubricant is selected from magnesium stearate, calcium stearate, stearic acid, sodium stearyl fumarate, sodium benzoate palmitic acid, talc, and colloidal silicon dioxide, glyceryl monostearate, glyceryl behenate, polyethylene glycol, sodium lauryl sulphate, and mixtures thereof. Glidant may be selected from amongst one or more of those suitable glidants known in the art. An example of a suitable, pharmaceutical^ acceptable glidant includes colloidal silicon dioxide. Antioxidant used in the composition is selected from butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), sodium ascorbate, sodium sulfite, tocopherol, citric acid, malic acid, ascorbic acid, and mixtures thereof. The chelating agent used is disodium edetate (EDTA) present in an amount of up to about 5% by weight of the composition. The composition of the present invention may be provided in the form of granules, powder, pellets, capsules, and tablets for oral administration. Alternatively, the composition may be provided in the form of orally disintegrating tablets. The composition in the form of granules, pellets or tablets is optionally film coated with a film coating layer comprising of film coating material. 16 Optionally, film coating layer may also comprise of plasticizer, colorant, pigment, lubricant, diluent, opacifier, etc. Film coating material is selected from the group of cellulose derivatives such as hydroxypropylmethylcellulose, hydroxypropylcellulose, ethylcellulose; Eudragits RTM such as Eudragit EPO, polyvinyl alcohol, Opadry RTM, Opadry AMB RTM (aqueous moisture barrier), Aquacoat RTM, povidone, polyvinyl acetate, etc. Plasticizer is selected from the group of hydrophilic and / or hydrophobic plasticizers and is selected from polyethylene glycol, triacetin, triethylcitrate, acetyl triethylcitrate, miglyol, cetyl alcohol, acetyltributylcitrate, diethyl phthalate, dibutyl phthalate, propylene glycol, hydrogenated oils, dibutylsebacate, meglumine and mixtures thereof and is preferably dibutyl sebacate. Plasticizers in the film coating layer is up to 30%, preferably from 5% to 20%, more preferably from 10% to 15% by weight of film forming layer. Any suitable natural, semi-synthetic, and synthetic colors, pigments, and flavors may be used. Preferred colors, pigments, and flavors are those that are listed in handbook of excipients. The invention is now described with non - limiting examples for the preparation of the composition comprising statin. Example 1: Atorvastatin Tablets 10mg Atorvastatin hemi calcium (amorphous form) (10.88 mg/tablet) was mixed with glycine (3.75 mg/tablet), lactose monohydrate (94.32 mg/tablet), microcrystalline cellulose PH 101 (25.0 mg/tablet), crospovidone (6.0 mg/tablet) and L-hydroxypropylcellulose (3.0mg/tablet) in a planetary 17 mixture for 10 minutes to obtain powder mixture. Butylated hydroxy anisole (0.15mg/tablet) and butylated hydroxy toluene (0.15mg/tablet) were dissolved in isopropanol. The solution was added to the powder mixture followed by addition of water under shear to obtain granules. The granules were dried in fluidized bed dryer at 55°C to 60°C. The dried granules were sieved through 30 mesh ASTM. Crospovidone (6.0 mg/tablet) was mixed with sieved granules in octagonal blender for 10 minutes followed by blending with magnesium stearate (2.25 mg/tablet) for 3 minutes. The resulting granules were compressed into tablets. The tablets were then coated with Opadry AMB (5.25 mg/tablet). The quantity in mg/tablet as given above can be adjusted accordingly to obtain the desired batch size. The tablets prepared above were packaged in induction sealed HDPE bottles with desiccants. These packed tablets were subjected to accelerated stability studies. Example 2: Atorvastatin Tablets 10mg Atorvastatin hemi calcium (crystalline form) (10.88 mg/tablet) was mixed with glycine (375 mg/tablet), lactose monohydrate (94.32 mg/tablet), microcrystalline cellulose PH 101 (25.0 mg/tablet), crospovidone (6.0 mg/tablet) and L-hydroxypropylcellulose (3.0mg/tablet) in a planetary mixture for 10 minutes to obtain powder mixture. Butylated hydroxy anisole (0.15 mg/tablet) and butylated hydroxy toluene (0.15mg/tablet) were dissolved in isopropanol. The solution was added to the powder mixture followed by addition of water under shear to obtain granules. The granules were dried in fluidized bed dryer at 55°C to 60°C. The dried granules were sieved through 30 mesh ASTM. Crospovidone (6.0 mg/tablet) was mixed with sieved granules in octagonal blender for 10 minutes followed by blending with magnesium stearate (2.25 mg/tablet) for 3 minutes. The resulting granules were compressed into tablets. The tablets were then coated with Opadry AMB (5.25 mg/tablet). The quantity in mg/tablet as given above can be adjusted accordingly to obtain the 18 desired batch size. The tablets prepared above were packaged in induction sealed HDPE bottles with desiccants. These packed tablets were subjected to accelerated stability studies at 40°C / 75% RH. The tablets prepared according to the above examples were subjected to dissolution testing in 0.5M phosphate buffer, pH 6.8 at 75 revolutions per minute using USP apparatus-ll. The results of the dissolution testing are provided in Table 1. Table 1: Dissolution profile of tablets of examples 1- 2 Time (Minutes) % Average Cumulative Drug Release Profile 15 Example 1 90 I" Example 2 -7—■ While the present invention has been described in terms of its specific embodiments, certain modifications and equivalents will be apparent to those skilled in the art and are intended to be included within the scope of the present invention. Dr. Ankur J. Shah Executive Director, Inventia Healthcare Private Limited 19

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