Field of the invention

The present invention relates to a stable solid oral dosage form of lipid-lowering agent. More particularly, the present invention relates to stable solid oral dosage form of atorvastatin or its pharmaceutically acceptable salts.

The present invention also relates to a process for the preparation of stable solid oral dosage form of atorvastatin or its pharmaceutically acceptable salts.

Background of the invention

Atorvastatin is a synthetic lipid-lowering agent. It is chemically known as [R-(R*,R*)]-2-(4-fluorophenyl)-p,5-dihydroxy-5-(l-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-lH-pynole-l-heptanoic acid and is disclosed in US 4,681,893. Further development has been made to develop various types of salt such as calcium salt of atorvastatin, which is disclosed in US 5,273,995.

Atorvastatin calcium act as a selective, competitive inhibitors of HMG-CoA reductase and is indicated for the treatment of hyperlipidaemia and hypercholesterolemia, both of which are risk factors for arteriosclerosis and coronary heart disease.

Atorvastatin calcium tablet dosage form is commercially available under the trade name Lipitor® in the United State. The inactive ingredients include calcium carbonate, candelilla wax, croscarmellose sodium, hydroxy propyl cellulose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, opadry white, polysorbate 80 and semethicone emulsion..

Atorvastatin calcium is insoluble in aqueous solutions of pH 4 and below, very slightly soluble in distilled water, pH 7.4 phosphate buffers and acetonitrile and slightly soluble in ethanol. It is available in various polymorphic forms such as amorphous as well as crystalline. But the use of amorphous form is more desirable rather than the crystalline form during formulation, due to its high solubility in the GI tract and ability to provide large active surface area, which ultimately increases the bioavailability. However, it is seen that amorphous atorvastatin calcium has very limited physical and chemical stability i.e. it has great tendency to undergo degradation forming the corresponding lactone, under normal storage conditions, which adversely affects its pharmaceutical efficacy and shelf life of the product. Further, it has very less micrometric properties such as flow ability and handling properties. Hence, many formulations have been reported for improving the storage stability of atorvastatin.

Given below are patents/patent publications, which disclose stable solid compositions of atorvastatin.

US 5,686,104 and US 6,126,971 disclose compositions comprising atorvastatin calcium along with one stabilizing pharmaceutically acceptable alkaline earth metal salt additives most preferably calcium carbonate to stabilize the composition.

US 6,531,507 and US 6,806,290 disclose a composition comprising a homogeneous mixture of a HMG-CoA reductase inhibitor including atorvastatin with a buffering substance or a basifying substance, wherein the composition has been obtained by co-crystallization and/or co-precipitation of said HMG-CoA reductase inhibitor and said buffering substance selected form the group consisting of salts of inorganic acids, salts of organic bases and/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 .

US 6,680,341 and US 2004/072894 disclose stable composition comprising HMG-CoA reductase inhibitors such as atorvastatin stabilized with various buffering agent such as sodium or potassium citrate, sodium phosphate, dibasic sodium phosphate, calcium carbonate, sodium or potassium hydrogen carbonate or lauryl sulphate, wherein the active composition has a pH in the range from 7 to 11.

US 6,911,472 discloses a stable composition comprising HMG-CoA reductase inhibitor including atorvastatin with an amino sugar.

US 7,030,151 discloses a composition containing atorvastatin calcium and a pH adjusting substance selected from the group consisting of metal oxides, inorganic bases, organic bases, and salts of organic and inorganic acids, prepared by granulation process.

us RE 39,502 discloses a stabilized pharmaceutical composition comprising atorvastatin and a stabilizing effective amount of at least one amido-group containing polymeric compound or at least one amino-group containing polymeric compound, or combination thereof; wherein said stabilized pharmaceutical composition does not contain a stabilizing effective amount of another stabilizer or a combination of other stabilizers.

US 2003/0175338 discloses a pharmaceutical formulation comprising particles of amorphous atorvastatin, wherein the particles have a particle size (dgo) less than 150^m and approximately 1.2% or less than 5% concentration of alkali metal additives. This patent publication further discloses composition of amorphous atorvastatin calcium using alkali metal salt additive, hydroxypropyl cellulose, povidone and other excipients.

US 2004/0247673 discloses a composition comprising wet granulated pharmaceutical composition of atorvastatin with less than about 5% weight of an alkaline earth metal salt additive comprising: (a) atorvastatin or a pharmaceutically acceptable salt thereof; and (b) a disintegrant or combination of disintegrants, wherein said wet granulated pharmaceutical composition contains not more than about 3% atorvastatin lactone based on the ratio of lactone peak area compared to the total drug-related peak integrated areas using HPLC.

US 2004/0253305 and US 2005/0032880 disclose a dry granulated pharmaceutical composition comprising atorvastatin or a pharmaceutically acceptable salt thereof wherein the composition contains less than about 5% (w/w) of an alkaline earth metal salt additive.

US 2005/0271717 and WO 04/110409 disclose a unit dosage form comprising atorvastatin or a pharmaceutically acceptable salt thereof, prepared without a granulation step, using alkalizing agent and binders such as povidone, pellulose etc.

US 2006/0093680 discloses a coated particle comprising an active ingredient including atorvastatin and a coating, wherein said coating comprises a film-forming substance selected from the group consisting of polyvinyl alcohol, a cellulose derivative and combinations thereof

US 2007/0190138 discloses a stable composition 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.

US 2007/0202159 discloses a process for preparation of stabilized statin particles comprising; i) dissolving/dispersing one or more stabilizers in solvent; spraying the solution/dispersion of stabilizers onto the amorphous statin and finally removing the solvent.

US 2007/116758 discloses a 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 atorvastatin is selected from group consisting of atorvastatin hemi-calcium Form V, atorvastatin having an average particle size of about 50^ and micronized atorvastatin. This patent publication discloses preparation of atorvastatin tablet using wet granulation.

US 2008/0038332 discloses a stabilized pharmaceutical formulation comprising an intimate admixture of atorvastatin calcium, one or more water-insoluble alkaline excipients, one or more antioxidants and at least one or more inert excipients or carriers.

US 2008/0051449 discloses a solid pharmaceutical composition comprising atorvastatin calcium Form VI and about 4 to about 10 percent by weight of a nonionic surfactant comprising polyoxyethylene sorbitan fatty acid ester.

WO 03/097039 discloses composition for oral administration comprising amorphous atorvastatin calcium and at least one sodium or potassium compound, such that either an aqueous dispersion of the composition is capable of providing a pH above 11.

WO 04/071402 discloses stable dosage form comprising one or more active substances sensitive to pH of the environment including atorvastatin and one or more pharmaceutical excipients which provide stability of one or more active substances to pH of the environment wherein said pharmaceutical dosage form does not contain any alkalizing or buffering substances or combinations thereof

WO 05/030183 discloses formulation of atorvastatin calcium together with magnesium stearate and sucrose stearate.

WO 06/054308 discloses a stable pharmaceutical formulation comprising a pharmaceutically acceptable form of atorvastatin as active ingredient, and at least one major excipient selected from the group consisting of starch, pregelatinized starch or lactose or a combination thereof.

WO 06/123358 discloses an 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.

WO 07/031801 discloses a composition for oral or sub-lingual administration comprising a HMG-CoA reductase inhibitor including atorvastatin or a pharmaceutical acceptable salt thereof and an effective amount of inorganic silica polymer such as dimethicone as a stabilizer to inhibit isomerization and/or elimination and/or oxidation and/or re- crystallisation.

WO 07/071012 discloses a composition of improved bioavailability and stability comprising atorvastatin calcium, a cyclodextrin, and a surfactant d-a tocopheryl polyethylene glycol 1000 succinate.

WO 07/082764 discloses a packaged pharmaceutical composition according to the invention, the composition comprises amorphous atorvastatin, a salt or ester thereof as active ingredient and an alkali metal additive selected from sodium hydroxide and potassium hydroxide and is exposed to an atmosphere comprising 1 to 16 % by volume of oxygen.

WO 07/100614 discloses non-crystalline solid atorvastatin salt dosage form comprising a non-crystalline solid atorvastatin salt and at least one pharmaceutical formulation excipient or carrier component wherein the formulation contain any stabilizers selected from the group consisting of salts of organic acids.

WO 2008/005543 discloses a composition comprising atorvastatin and at least one of a biodegradable binder or lipophilic binder with reduced food effect.

WO 2008/039894 discloses a formulation comprising two discrete portions of atorvastatin in which mixture of 10-50% of atorvastatin and acid solubility enhancing excipient comprising rnethacrylic acid copolymer is in the intragranular portion and remaining atorvastatin in extragranular portion.

WO 2008/082124 discloses a composition with improved storage stability comprising atorvastatin calcium salt and 10-20 wt % of a polymer comprising polyethylene oxide group selected from the group consisting of polyethylene oxide, poloxamer, polyethylene glycol, Gelucire or its derivatives.

WO 2008/106901 discloses an oblong or round shaped tablet core comprising atorvastatin, organic or inorganic base selected from meglumine or an alkali metal hydroxide and a coating over the core.

WO 2008/117154 claims a composition comprising HMG-CoA reductase inhibitor, polyethylene glycol and an alkalizing agent selected from the group consisting of meglumine, tromethamine, sodium carbonate, sodium bicarbonate, sodium citrate, potassium citrate, dibasic sodium phosphate, tribasic sodium phosphate, sodium hydroxide, potassium hydroxide and mixtures thereof

WO 2008/152598 discloses a composition comprising atorvastatin, combination of pregelatinized starch and mannitol as diluent and an alkanizing agent which inalkali metal salt additives or alkaline earth metal salt additives.

WO 2009/000286 discloses a composition comprising a HMG-CoA reductase inhibitor and an effective amount of colloidal clay such as attapulgite as a stabilizer.

WO 2009/013633 discloses an amoi-phous co-precipitate comprising atorvastatin and a hydrophilic carrier selected from the group comprising povidone (polyvinylpyrrolidone), polyvinyl alcohol, hydroxypropyl methylcellulose, methylcellulose, carboxymethyl cellulose, sodium carboxymethyl cellulose, hydroxyethylcellulose, polyvinyl acetate, cyclodextrins, gelatins, hypromellose phthalate, sugars, and combinations.

WO 2009/016358 discloses a composition comprising one or more cholesterol reducing agents in an amorphous form in combination with a polymeric carrier, and optionally at least one excipient prepared by hot melt extrusion.

IN 529/MUM/2006 discloses a composition comprising HMG CoA reductase inhibitors, free of alkalizing agents, polyether and pharmaceutically acceptable excipients.

The above prior art references disclose various solid dosage formulations of atorvastatin, using alkali metal salt stabilizers, binders such as povidone, cellulose derivatives, starch prepared by granulation or direct compression. However, still there is a need to develop stable formulations of atorvastatin, prepared by simple and cost effective process. The inventors of the present invention during their continuous efforts to develop stable formulation of atorvastatin found that formulations containing alkaline stabilizer, copovidone prepared by direct compression improves the overall stability of amorphous atorvastatin calcium and at the same time bioequivalent to the marketed dosage form.

Objective of the invention

Accordingly, the main objective of the present invention is to provide stable solid oral dosage form of atorvastatin or its pharmaceutically acceptable salts.

Yet another objective of the present invention is to provide a stable solid oral dosage form of atorvastatin or its pharmaceutically acceptable salts in such a way that it will comply with the reference product in terms of in vivo parameters like bioequivalence such as Cmax, AUC, T„,ax and in vitro parameters like dissolution, disintegration etc.

Yet another objective of the present invention is to provide a simple process for the preparation of stable solid oral dosage form of atorvastatin or its pharmaceutically acceptable salts,

Summary of the invention

Accordingly, the present invention provides a stable solid oral dosage form of atorvastatin comprising amiorphous atorvastatin or its pharmaceutically acceptable salt, about 2 to 20% by weight of alkali metal salt stabilizer and about 2 to 20% by weight of copovidone, prepared by direct compression.

Detailed description of the invention

The stable solid dosage form of atorvastatin of the present invention, further comprise one or more pharmaceutically acceptable excipients selected from the group consisting of diluents, disintegrants, antioxidants, surfactants, glidants, lubricants and the like.

In an embodiment of the present invention, alkali metal salt stabilizer include sodium carbonate, sodium bicarbonate, sodium hydroxide, potassium carbonate, potassium bicarbonate, potassium hydroxide, sodium silicate, disodium hydrogen orthophosphate, sodium dihydrogen phosphate, sodium phosphate, dihydroxy aluminum sodium carbonate (DASC) and sodium aluminates or combinations thereof. The alkali metal salt used may be in the range of about 2% to about 20% by weight of the composition. More preferably, the alkali metal salt may be used in the range of about 2% to about 10% by weight of the composition.

Copovidone is a synthetic copolymer of N-vinyl-2-pyrrolidone and vinyl acetate. Co sifting of copolymer such as copovidone with amorphous atorvastatin calcium results in coating of atorvastatin calcium particles thereby acting as a stabilizer to inhibit isomerization and/or elimination and/or oxidation and/or recrystallisation. Moreover, copovidone is more flexible film former than povidone, which is suitably used as a tablet binder in direct compression and dry granulation.

Further, copovidone is more preferred over povidone for use with moisture sensitive drug due to its low hygroscopicity. Moreover, copovidone has excellent flow properties, due to its spherical particle morphology and narrow particle-size distribution.

In an embodiment, the copovidone used may be in the range of about 2% to about 20% by weight of the composition.

Suitable diluents used according to the present invention are selected from lactose, microcrystalline cellulose, sucrose, starch, polyols such as mannitol, sorbitol, xylitol, maltitol and the like or combinations thereof. The diluents may be used in the range of about 50 to 90% by the weight of the composition.

Suitable disintegrants used according to the present invention are selected from croscarmellose sodium, sodium starch glycolate, carboxymethylcellulose and its salts, cross-linked polyvinylpyrrolidone and the like or combinations thereof. The disintegrants may be used in the range of about 1 to 15% by the weight of the composition.

Suitable antioxidants used according to the present invention are selected from butylated hydroxy anisole, butylated hydroxy toluene, ascorbic acid, sodium ascorbate and the like or combinations thereof. The antioxidants may be used in the range of about 0.01 to 0.5% by the weight of the composition.

Suitable surfactants used according to the present invention are selected from sorbitan monolaurate, polysorbate 80, sodium lauryl sulfate, poloxamer and the like or combinations thereof. The surfactant may be used in the range of about 0.2 to 5% by the weight of the composition.

Suitable lubricants used according to the present invention are selected from magnesium stearate, calcium stearate, sodium stearyl fumarate, stearic acid, fumaric acid, palmitic acid, glyceryl behenate and the like or combinations thereof. The lubricant may be used in the range of about 1 to 5% by the weight of The composition.

Suitable glidants include talc, silicon dioxide, cornstarch and the like.

The pharmaceutically acceptable salts of the present invention include sodium, potassium, calcium, magnesium, zinc and the like.

In yet another embodiment of the present invention, the amount of atorvastatin used may be in the range of about 5% to about 20% by weight of the composition.

In a preferred embodiment of the present invention, the dosage form comprises about 5% to about 20% by weight of amorphous atorvastatin; about 2% to about 20% by weight of alkali metal salt selected from sodium carbonate, potassium carbonate and dihydroxy aluminium sodium carbonate; about 2% to about 20% by weight of copovidone; about 50 to 90% by weight of diluent selected from lactose, microcrystalline cellulose and mannitol; about 1 to 15% by weight of disintegrant selected from croscarmellose sodium, sodium starch glycolate and cross-linked polyvinylpyrrolidone; about 0.01 to 0.5% by weight of antioxidant selected from butylated hydroxy anisole, butylated hydroxy toluene and ascorbic acid; about 0.2 to 5% by weight of surfactant selected from polysorbate 80, sodium lauryl sulfate and poloxamer; about 1 to 5% by the weight of lubricant selected from magnesium stearate, sodium stearyl fumarate and stearic acid prepared by direct compression.

The solid dosage form of the present invention may be in the form of capsules or tablets, wherein the tablets may be uncoated or optionally coated with film coating/moisture barrier coating composition. The coating solution mainly comprises of film forming polymers and one or more of plasticizers, opacifier, anti tacking agents and the like. The coating according to the present invention is applied by solubilising or suspending the excipients in solvents such as isopropyl alcohol, water, acetone, ethanol, methylene chloride and the like or mixtures thereof

Suitable film forming polymers used according to the present invention are selected from hydroxypropylmethyl cellulose, hydroxypropyl cellulose hydroxy ethyl cellulose, polyvinyl alcohol and the like. The coating can also be performed using any commercially available ready to coat preparations such as opadry-AMB, opadry-white, opadry-clear, etc.

Suitable plasticizers used according to the present invention are selected from diethyl phthalate, bis-2-ethylhexyl phthalate, triacetin, polyethylene glycol and the like.

The present invention also provides a process for the preparation of stable solid oral dosage form of atorvastatin comprising amorphous atorvastatin or its pharmaceutically acceptable salt, about 2 to 20% by weight of alkali metal salt stabilizer and about 2 to 20% by weight of copovidone, prepared by direct compression comprising the steps of:

1) blending atorvastatin or its pharmaceutically acceptable salts with copovidone, diluent, alkali metal salt stabilizer,

2) separately mixing surfactant and antioxidant,

3) mixing the blend of step (1) to the blend obtained in step (2),

4) lubricating the blend of step (3),

5) compressing the lubricated blend to obtain tablets and

6) finally coat the tablets with film forming materials.

Alternatively, the stable solid oral dosage form of atorvastatin comprising amorphous atorvastatin or its pharmaceutically acceptable salt, about 2 to 20% by weight of alkali metal salt stabilizer and about 2 to 20% by weight of copovidone, may also be prepared by direct compression comprising the steps of:

1) blending atorvastatin or its pharmaceutically acceptable salts with copovidone,

2) mixing alkali metal salt with the blend of step (1) followed by disintegrant,

3) dissolving a mixture of surfactants and antioxidant in a solvent,

4) adsorbing the solution of step (3) on the surface of diluent followed by drying for about 45mins,

5) mixing the blend of step (4) with the blend obtained in step (2) followed by diluent,

6) lubricating the blend of ste;p (5),

7) compressing the lubricated blend to obtain tablets and

8) finally coat the tablets with film forming materials.

In another embodiment of the present invention, there is provided a method of treating hyperlipidaemia, hypercholesterolemia and preventing the risk of cardiovascular diseases comprising administering the solid dosage form of atorvastatin prepared according to the present invention.

The following examples further exemplify the invention and are not intended to limit the scope of the invention. It is obvious to those skilled in the art to find out the composition for other dosage forms and substitute the equivalent excipients as described in this specification or with the one known to the industry.

Example 1

S.No. Ingredients Qty/tab(mg)
1 Atorvastatin calcium [amorphous] equivalent to Atorvastatin 80 mg 86.80
2 Sodium carbonate anhydrous 30.00
3 Copovidone 100.00
4 Lactose anhydrous 300.00
5 Mannitol 582.80
6 Croscarmellose sodium 72.00
7 Polysorbate 80 15.00
8 Butylated hydroxy anisole 1.00
9 Butylated hydroxy toluene 0.40
10 Magnesium stearate 12.00
Film coating
11 Opadry white / Opadn,' white AMB 45.00
12 Purified water q.s
Coated tablet weight 1245.00

The processing steps involved in manufacturing stable solid oral dosage form of atorvastatin are given below:

i) amorphous atorvastatin calcium and copovidone were sifted and blended,

ii) anhydrous sodium carboneite was sifted and blended with blend of step (i) followed by mixing croscarmellose sodium.

iii) dissolved the polysorbate 80, butylated hydroxy anisole and butylated hydroxy toluene in isopropyl alcohol,

iv) adsorbed the solution of step (iii) over anhydrous lactose followed by drying,

v) mixed the material obtained in step (iv) to the blend of step (ii),

vi) sifted mannitol and blended with materials obtained in step (v)

vii) sifted magnesium stearate and lubricated the blend of step (vi),

viii) compressed the lubricated blend of step (vii) to obtain tablet,

ix) prepared the film coating solution and

x) coated the tablets to obtain film coated tablets.

The compositions given in examples 2 to 5 were prepared using similar procedure described in example 1.

Example 2

S.No. Ingredients Qty/tab(mg)

1 Atorvastatin calcium [amorphous] equivalent to Atorvastatin 80 mg 86.80
2 Sodium carbonate anhydrous 30.00
3 Copovidone 100.00
4 Lactose anhydrous 350.00
5 Mannitol 526.80
6 Croscarmellose sodium 72.00
7 Sodium lauryl sulfate 15.00
8 Butylated hydroxy anisole 1.00
9 Butylated hydroxy toluene 0.40
10 Magnesium stearate 18.00
Film coating
11 Opadry white / Opadr/ white AMB 45.00
12 Purified water q.s
Coated tablet weight 1245.00

Example 3

S.No. Ingredients Qty/tab(mg)
1 Atorvastatin calcium [amorphous] equivalent to Atorvastatin 80 mg 86.80

2 Sodium carbonate anhydrous 30.00

3 Copovidone 100.00

4 Lactose anhydrous 300.00

5 Microcrystalline cellulose 582.80

6 Croscarmellose sodium 72.00

7 Polysorbate 80 15.00

8 Butylated hydroxy anisole 1.00

9 Butylated hydroxy toluene 0.40

10 Magnesium stearate 12.00 Film coating

11 Opadry white / Opadry white AMB 45.00

12 Purified water q.s Coated tablet weight 1245.00

Example 4

S.No. Ingredients Qty/tab(mg)

1 Atorvastatin calcium (amorphous] equivalent to Atorvastatin 80 mg 86.80

2 Potassium carbonate anhydrous 30.00

3 Copovidone 100.00

4 Lactose anhydrous 300.00

5 Mannitol 576.80

6 Croscarmellose sodium 72.00

7 Polysorbate 80 15.00

8 Butylated hydroxy anisole 1.00

9 Butylated hydroxy toluene 0.40

10 Magnesium stearate 18.00
Film coating

11 Opadry white / Opadry white AMB 45.00

12 Purified water q.s
Coated tablet weight 1245.00

Example 5

S.No. Ingredients Qty/tab(mg)
1 Atorvastatin calcium [amorphous] equivalent to Atorvastatin 80 mg 86.80
2 Dihydroxy aluminium sodium carbonate 30.00
3 Copovidone 100.00
4 Lactose anhydrous 300.00
5 Mannitol 576.80
6 Croscarmellose sodium 72.00
7 Polysorbate 80 15.00
8 Butylated hydroxy anisole 1.00
9 Butylated hydroxy toluene 0.40
10 Magnesium stearate 18.00
Film coating
11 Opadry white / Opadrj^ white AMB 45.00
12 Purified water q.s
Coated tablet weight 1245.00

Dissolution profile of atorvastatin tablets prepared according to example 2 of the present invention was carried out in pH 6.8 phosphate buffer as dissolution medium using USP

Apparatus II with 900 ml at 75 rpm speed. The release profile (% drug dissolved in min) is given in Table 1.

Table 1

Time (min) % Drug dissolved
10 33
15 53
30 75
45 84
60 89
75 93
90 95

The tablets of atorvastatin prepared according to the example 2 of the present invention were found to be stable. The stability data obtained after 6 months at 40°C/ 75% RH is shown in Table 2.

Table 2

Test period Total impurities
(% w/w)
Initial 0.195
After 1 month 0.166
After 2 months 0.193
After 3 months 0.207
After 6 months 0.313

We claim:

1. A stable solid oral dosage form comprising amorphous atorvastatin or its pharmaceutically acceptable salt, about 2 to 20%o by weight of alkali metal salt stabilizer and about 2 to 20% by weight of copovidone, prepared by direct compression.

2. The dosage form as claimed in claim 1, wherein the alkali metal salt stabilizer is selected from sodium carbonate, sodium bicarbonate, sodium hydroxide, potassium carbonate, potassium bicarbonate, potassium hydroxide, sodium silicate, disodium hydrogen orthophosphate, sodium dihydrogen phosphate, sodium phosphate, dihydroxy aluminum sodium carbonate (DASC) and sodium aluminates or combinations thereof

3. The dosage form as claimed in claim 1, wherein the dosage form further comprises one or more pharmaceutically acceptable excipients selected from diluents, disintegrants, antioxidants, surfactants, glidants and lubricants.

4. The dosage form as claimed in claim 3, wherein the diluent is selected from lactose, microcrystalline cellulose, sucrose, starch, polyols such as mannitol, sorbitol, xylitol, maltitol or combinations thereof

5. The dosage form as claimed in claim 3, wherein the disintegrant is selected from croscarmellose sodium, sodium starch glycolate, carboxymethylcellulose and its salts, cross-linked polyvinylpyrrolidone or combinations thereof

6. The dosage form as claimed in claim 3, wherein the antioxidant is selected from butylated hydroxy anisole, butylated hydroxy toluene, ascorbic acid, sodium ascorbate or combinations thereof

7. The dosage form as claimed in claim 3, wherein the surfactant is selected from sorbitan monolaurate, polysorbate 80, sodium lauryl sulfate, poloxamer or combinations thereof.

8. A stable solid oral dosage form comprising amorphous atorvastatin or its pharmaceutically acceptable salt, about 2 to 20%) by weight of alkali metal salt stabilizer and about 2 to 20% by weight of copovidone prepared by direct compression comprising the steps of:

i) blending atorvastatin or its pharmaceutically acceptable salts with copovidone,

ii) mixing alkali metal salt with the blend of step (i) followed by disintegrant,

iii) dissolving a mixture of surfactant and antioxidant in a solvent,

iv) adsorbing the solution of step (iii) on the surface of diluent followed by drying for about 45 mins,

v) mixing the blend of step (iv) with the blend obtained in step (ii) followed by diluent,

vi) lubricating the blend of step (v),

vii) compressing the lubricated blend to obtain tablets.

9. A stable solid oral dosage form comprising about 5% to about 20% by weight of amorphous atorvastatin; about 2% to about 20% by weight of alkali metal salt selected from sodium carbonate, potassium carbonate and dihydroxy aluminium sodium carbonate; about 2% to about 20% by weight of copovidone; about 50 to 90% by weight of diluent selected from lactose, microcrystalline cellulose and mannitol; about 1 to 15% by weight of disintegrant selected from croscarmellose sodium, sodium starch glycolate and cross-linked polyvinylpyrrolidone; about 0.01 to 0,5% by weight of antioxidant selected from butylated hydroxy anisole, butylated hydroxy toluene and ascorbic acid; about 0.2 to 5% by weight of surfactant selected from polysorbate 80, sodium lauryl sulfate and poloxamer; about 1 to 5% by the weight of lubricant selected from magnesium stearate, sodium stearyl fumarate and stearic acid prepared by direct compression.