WO2006001029A2

WO2006001029A2 - Antiretroviral compositions

Info

Publication number: WO2006001029A2
Application number: PCT/IN2004/000184
Authority: WO
Inventors: Pothireddy Venkateswar Reddy; Muppidi Vanaja
Original assignee: Hetero Drugs Limited
Priority date: 2004-06-25
Filing date: 2004-06-25
Publication date: 2006-01-05
Also published as: WO2006001029A3

Abstract

The present invention provides stable pharmaceutical formulations for a combination product of zidovudine, lamivudine and nevirapine. Thus, for example, the present invention provides a stable tablet formulation comprising zidovudine, lamivudine, nevirapine, microcrystalline cellulose, starch, croscarmellose sodium, polyvinylpyrrolidone, magnesium stearate, colloidal anhydrous silica, crospovidone and a coating of hydroxypropyl(methyl)cellulose.

Description

ANTIRETROVIRAL COMPOSITIONS

FIELD OF THE INVENTION The present invention relates to stable pharmaceutical compositions of antiretrovirals. BACKGROUND OF THE INVENTION Zidovudine, chemically, 3'-Azido-3'-deoxythymidine; azidothymidine; or AZT is a reverse transcriptase inhibitor. The therapeutic uses of zidovudine and related compounds, and their preparations were disclosed in U.S. Patent No. 4,724,232. Zidovudine is commercially available as 100 mg capsule, 300 mg tablet, 10 mg/mL in 20-mL single-use vial and 50 mg/5 mL in 240 mL syrup. It is sold under the name RETROVIR. Lamivudine, chemically, (2R-cis)-4-Amino-1-[2-(hydroxymethyl)-1 ,3- oxathiolan-5-yl]-2(/H)-pyrimidinone; (-)-2'-deoxy-3'-thiacytidine; (-)-1-[(2f?,5S)-2- (hydroxymethyl)-i ,3-oxathiolan-5-yl]cystosine; or 3TC is a reverse transcriptase inhibitor. The therapeutic uses of lamivudine and related compounds and their preparations were disclosed in WO 91/17159. Lamivudine is commercially available as 100 mg, 150 mg and 300 mg tablets; 10 mg/mL in 240 mL oral solution. It is sold under the name EPIVIR. The combination of lamivudine and zidovudine is commercially available as 150 mg and 300 mg tablets. It is sold under the name COMBIVIR. Stavudine, chemically, 2', 3'-Didehydro-3'-deoxythymidine; 1-(2,3- dideoxy-β-g/ycero-pent-2-enofuranosyl)thymine; or 3'-deoxy-2'-thymidinene is a reverse transcriptase inhibitor. The therapeutic uses of stavudine and related compounds and their preparations were disclosed in U.S. Patent No. 5,130,421. Stavudine is commercially available as 15 mg, 20 mg, 30 mg and 40 mg capsules; and 1 mg/mL in 200 ml oral solution. It is sold under the name ZERIT. Nevirapine, chemically, 11-Cyclopropyl-5,11-dihydro-4-methyl-6/-/- dipyrido[3,2-b: 2', 3'-e][1 ,4]diazepin-6-one is a non-nucleoside reverse transcriptase inhibitor (NNRTI). The therapeutic uses of nevirapine and related compounds and their preparations were disclosed in U.S. Patent No. 5,366,972. Nevirapine is commercially available as 200 mg tablet and 50 mg/5 mL in 240 mL oral suspension. It is sold under the name VIRAMUNE. U.S. Patent No. 6,113,920 disclosed a pharmaceutical composition comprising two active pharmaceutical ingredients namely lamivudine and zidovudine and a pharmaceutically acceptable glidant ingredient in the form of a film coated tablet. The PCT application WO 00/18383 disclosed antiviral combination of (S)-2-ethyl-7-fluoro-3-oxo-3,4-dihydro-2H-quinoxaline-1 -carboxylic acid isopropyl ester and zidovudine and/or lamivudine. The PCT application WO 96/01110 described a combination of zidovudine, lamivudine and lovi.ride for the treatment of HIV infections and AIDS. All the above mentioned patents are incorporated by references. A high dosage strength combination oral dosage forms of antiretroviral having satisfactory stability has not been successfully developed prior to the present invention. The object of the present invention is to provide stable high dosage strength combination oral dosage forms of antiretrovirals.

DETAILED DESCRIPTION OF THE INVENTION The present invention provides stable pharmaceutical formulations for combination products of i) zidovudine, lamivudine and nevirapine; ii) lamivudine and stavudine; and iii) nevirapine, lamivudine and stavudine tablets. The pharmaceutical composition may be for example, in the form of a tablet, a caplet, a pellet, a capsule, a granule, a pil, a powder or a sachet. Preferably the pharmaceutical composition is in the form of a tablet. The capsule may contain a powder, a compressed powder or a granule. The pharmaceutical composition of the present invention is administered orally. In developing new tablet dosage formulations, it is necessary to balance the often-competing needs of marketing and production areas. In order to properly do so, each tablet much is uniform in weight and contains the appropriate amount of active ingredient, good flowability of formulations. The tablet formulations must be physically and chemically stable. Proper choice of method of manufacture and selection of excipients is critical. The active component of each tablet must be readily available as needed; hence the tablets must have the proper type of drug release and the appropriate dissolution characteristics. The tablets must have the mechanical integrity to withstand damage during manufacturing, packaging and use. The chosen method of manufacture must be efficient, reproducible, and amenable to automation. The tablets must be elegant in appearance. Excipient selection depends on various factors, such as, the choice of 5 active ingredient percentage, the objectives of the tablet formulation development and method of manufacture. The foremost property an excipient must possess is compatibility with active ingredients. 1) Zidovudine, lamivudine and nevirapine formulation: The present invention provides a formulation suitable for forming tablet io comprising in parts by weight from about 25% to about 35% zidovudine, from about 15% to about 25% nevirapine, from about 10% to about 20% lamivudine, from about 10% to about 30% microcrystalline cellulose, from about 2.5% to about 10% starch, from about 1.0% to about 2.5% croscarmellose sodium, from about 1.0% to about 2.0% polyvinylpyrrolidone K-30, from about 1.0% to about 15 2.0% magnesium stearate, from about 0.5% to about 1.5% colloidal anhydrous silica, from about 1.5% to about 3% crospovidone, from about 1.75% to about 2.5% opadry white. Optionally additional excipient/s may be used. The additional excipients include pharmaceutical lubricants, disintegrators, binders, glidents, fillers or mixtures thereof. 20 The preferable tablet formulation is zidovudine (300 mg), nevirapine (200 mg) and lamivudine (150 mg), which comprises in parts by weight from about 28% to about 33% zidovudine, from about 14% to about 17% lamivudine, from about 18% to about 22% nevirapine, from about 17% to about 20% microcrystalline cellulose, from about 6% to about 7.5% starch, from about 1.5% 25 to about 2% croscarmellose sodium, from about 1.5% to about 2.0% polyvinylpyrrolidone K-30, from about 1.25% to about 1.75% magnesium stearate, from about 0.75% to about 1 % colloidal anhydrous silica, from about 11.5% to about 2% crospovidone and about 2% opadry white. 2) Lamivudine and stavudine formulation: ^• 30 The present invention provides a formulation suitable for forming tablet comprising in parts by weight from about 25% to about 35% lamivudine, from about 4% to about 10% stavudine, from about 10% to about 25% microcrystalline cellulose, from about 20% to about 35% lactose, from about 5% to about 15% starch, from about 0.5% to about 2.5% croscarmellose sodium, from about 0.1% to about 0.6% lake sunset yellow or lake quinoline yellow, from about 0.5% to about 5% polyvinylpyrrolidone k-30, from about 1 % to about 3% magnesium stearate, from about 0.25% to about 2% colloidal anhydrous silica and from about 1.0% to about 3% sodium starch glycollate. Optionally additional excipient/s may be used. The additional excipients include pharmaceutical lubricants, disintegrators, binders, glidents, fillers or mixtures thereof. The preferable tablet formulations are: i) Lamivudine (150 mg) and stavudine(30 mg) tablets; which comprises in parts by weight from about 28% to about 32% lamivudine, from about 5.5% to about 6.5% stavudine, from about 14% to about 18% microcrystalline cellulose, from about 26% to about 31% lactose, from about 9% to about 11 % starch, from about 1.5% to about 2% croscarmellose sodium, from about 0.3% to about 0.5% lake sun set yellow, from about 1.5% to about 2.5% polyvinylpyrrolidone K-30, from about 1.5% to about 2.5% magnesium stearate, from about 0.5% to about 1% colloidal anhydrous silica and from about 2.25 to about 3% sodium starch glycollate; ii) Lamivudine(150mg) and stavudine(40mg) tablets; which comprises in parts by weight from about 28% to about 32% lamivudine, from about 7% to about 9% stavudine, from about 14% to about 17% microcrystalline cellulose, from about 25% to about 30% lactose, from about 9% to about 11% starch, from about 1.5% to about 2% croscarmellose sodium, from about 0.3% to about 0.5% lake quinolline yellow, from about 1.5% to about 2.5% polyvinylpyrrolidone K-30, from about 1.5% to about 2.5% magnesium stearate, from about 0.5% to 1.0% colloidal anhydrous silica and from about 2.25% to about 3.0% sodium starch glycollate. 3) Nevirapine, lamivudine and stavudine formulation: The present invention provides a formulation suitable for forming tablet comprising in parts by weight from about 20% to 35% nevirapine, from about 15% to about 25% lamivudine, from about 2% to about 8% stavudine, from about 23% to about 35% lactose, from about 5% to about 10% starch, from about 0.5% to about 4% croscarmellose sodium, from about 0.1% to about 0.4% lake sunset yellow or lake quinoline yellow, from about 1% to about 3.5% polyvinylpyrrolidone k-30, from about 1.0% to about 2.5% magnesium stearate, from about 0.5% to about 1.5% colloidal anhydrous silica and from about 1.0% to about 4.0% sodium starch glycollate. Optionally additional excipient/s may be used. The additional excipients include pharmaceutical lubricants, disintegrators, binders, glidents, fillers or mixtures thereof. The preferable tablet formulations are: i) Nevirapine(200mg), lamivudine(150mg) and stavudine(30mg) tablets; which comprises in parts by weight from about 26% to about 31% nevirapine, from about 19% to about 23% lamivudine, from about 4% to about 4.5% stavudine, from about 25% to about 30% lactose, from about 7% to about 8.5 % starch, from about 2% to about 2.5% croscarmellose sodium, from about 0.25% to 0.35% lake sun set yellow, from about 2% to about 3% polyvinylpyrrolidone K-30, from about 1.5% to about 2% magnesium stearate, from about 0.5% to 1.25% colloidal anhydrous silica and from about 2.5% to about 3% sodium starch glycollate; ii) Nevirapine(200mg), lamivudine(150mg) and stavudine(40mg) tablets; which comprises in parts by weight from about from about 26% to about 31 % nevirapine, from about 19% to about 23% lamivudine, from about 5% to about 6.5% stavudine, from about 25% to about 32% lactose, from about 7 to about 8.5% starch, from about 1.5 to about 2.5% croscarmellose sodium, from about 0.25 to about 0.35% lake quinoline yellow, from about 2% to about 3% polyvinylpyrrolidone K-30, from about 1.5% to about 2% magnesium stearate, from about 0.5 to about 1.25% colloidal anhydrous silica and from about 2.5% to 3% sodium starch glycollate. Stable mixture, which is highly compressible, have good flow properties, thereby providing the tablets with excellent physical properties. The filler includes, but is not limited to calcium carbonate, dibasic calcium phosphate, lactose, magnesium carbonate, magnesium oxide, lactose anhydrous, microcrystalline cellulose, mannitol or mixtures thereof. The lubricant includes, but is not limited to stearic acid, a salt of stearic acid, talc, sodium stearyl fumarate, glyceryl behenate, magnesium silicate, magnesium trisilicate, hydrogenated castor oil or mixtures thereof. Preferably, the disintegrator includes, but is not limited to sodium starch glycolate, starch, croscarmellose sodium, crospovidone, carboxymethyl cellulose calcium, carboxymethylcellulose sodium, magnesium aluminium silicate or mixtures thereof. The glidents may be for example colloidal anhydrous silica, talc or mixtures thereof. The binder includes, hydroxypropyl cellulose, polyvinylpyrrolidone k-30, hydroxypropyl cellulose(low-substituted), starch or mixtures thereof. Other ingredients such as diluents, stabilizers and antiadherants, conventionally used for pharmaceutical formulations may be included in the present formulation.

The following examples illustrate the present invention without, however, limiting the same thereof.

EXAMPLES A composition according to the present invention was prepared as follows. The specific components used are detailed in following examples.

ZIDOVUDINE(SOOMG), NEVIRAPINE (200MG) AND LAMIVUDINE (150MG) COMBINATION TABLETS: A pharmaceutical composition was prepared according to the method of example 1. An active ingredients zidovudine, lamivudine and nevirapine and a mixture of microcrystalline cellulose, starch, croscarmellose sodium, polyvinylpyrrolidone K-30, magnesium stearate, colloidal anhydrous silica, crospovidone, opadry white, isopropyl alcohol and dichloromethane.

Example 1 The components and their amounts was as follows:

The above formulation was prepared as follows. Granulation of active ingredients including zidovudine(300mg), lamivudine(150mg), nevirapine(200mg) with additives like microcrystalline cellulose(184mg), starch(66mg) and croscarmellose sodium(9mg) was done in a planetary mixer and mixed for 5 to 20 minutes. Binder solution (polyvinylpyrrolidone K-30 (16mg) in purified water) is added to contents of planetary mixer and mixed to get dough mass. The dough mass was dried, and dried granules passed through #16. The blending of ingredients including above dried granules, magnesium stearate(15mg), croscarmellose sodium(9mg), colloidal anhydrous silica(8mg) and crospovidone(18mg) in a blender and mix for 5 to 10 minutes. The final blend was compressed into 975 mg tablets using compression machine. Coating solution was prepared by using 19.5mg of opadry white with required quantity of isopropyl alcohol and required quantity of dichloromethane.

LAMIVUDINE AND STAVUDINE COMBINATION TABLETS: A pharmaceutical composition was prepared according to the method of examples 2 and 3. An active ingredients lamivudine , stavudine and a mixture of microcrystalline cellulose, lactose, starch, croscarmellose sodium, polyvinylpyrrolidone K-30, lake quinoline yellow, lake sunset yellow, sodium starch glycollate, magnesium stearate and colloidal anhydrous silica.

Example 2 The components and their amounts was as follows: Lamivudine (150mg) and stavudine(30mg) tablets:

The above formulation was prepared as follows. Granulation of active ingredients including lamivudine(150mg), stavudine(30mg) with additives like microcrystalline cellulose(δθmg), lactose(143.5mg), starch(50mg), croscarmellose sodium(3.5mg) and lake sunset yellow(2mg) was done in a planetary mixer and mixed for 5 to 20 minutes. Binder solution (polyvinylpyrrolidone K-30 (10mg) in purified water) is added to contents of planetary mixer and mixed to get dough mass. The dough mass was dried, and dried granules passed through #18. The blending of ingredients above dried granules, magnesium stearate(10mg), croscarmellose sodium(5mg), colloidal anhydrous silica(4mg) and sodium starch glycollate(12mg) in a blender and mix for 5 to 10 minutes.

Example 3 The components and their amounts was as follows: Lamivudine (150mg) and stavudine(40mg) tablets.

The above formulation was prepared as follows. Granulation of active ingredients including lamivudine(150mg), stavudine(40mg) with additives like microcrystalline cellulose(75mg), lactose(138.5mg), starch(50mg), croscarmellose sodium(3.5mg) and lake quinolline yeilow(2mg) was done in a planetary mixer and mixed for 5 to 20 minutes. Binder solution (polyvinylpyrrolidone K-30(10mg) in purified water) is added to contents of planetary mixer and mixed to get dough mass. The dough mass was dried, and dried granules passed through #18. The blending of ingredients above dried granules, magnesium stearate(IOmg), croscarmellose sodium(5mg), colloidal anhydrous silica(4mg) and sodium starch glycollate(12mg) in a blender and mix for 5 to 10 minutes. The final blend was compressed into 500mg tablets using compression machine. NEVIRAPINE, LAMIVUDINE AND STAVUDINE COMBINATION TABLETS: A pharmaceutical composition was prepared according to the method of examples 4 and 5. An active ingredients nevirapine, lamivudine, stavudine and a mixture of lactose, starch, croscarmellose sodium, polyvinylpyrrolidone K-30, lake quinoline yellow, lake sunset yellow, magnesium stearate, sodium starch glycollate and colloidal anhydrous silica. Example 4 The components and their amounts were as follows: Nevirapine (200mg), lamivudine (150mg) and stavudine(30mg) tablets.

The above formulation was prepared as follows. Granulation of active ingredients including nevirapine(200mg), lamivudine(150mg), stavudine(30mg) with additives like lactose(193.1mg), starch(55.4mg), croscarmellose sodium(9mg) and lake sunset yellow(2mg) was done in a planetary mixer and mixed for 5 to 20 minutes. Binder solution (polyvinylpyrrolidone K-30 (17mg) in purified water) is added to contents of planetary mixer and mixed to get dough mass. The dough mass was dried, and dried granules passed through #18. The blending of ingredients above dried granules, magnesium stearate(11.5mg), croscarmellose sodium(6mg), colloidal anhydrous silica(7mg) and sodium starch glycollate(19mg) in a blender and mix for 5 to 10 minutes. The final blend was compressed into 700mg tablets using compression machine. Example 5 The components and their amounts was as follows: Nevirapine (200mg), lamivudine (150mg) and stavudine(40mg) tablets.

The above formulation was prepared as follows. Granulation of active ingredients including nevirapine(200mg), lamivudine(150mg), stavudine(40mg) with additives like lactose(183.1mg), starch(55.4mg), croscarmellose sodium(9mg) and lake q.uinolline yel!ow(2mg) was done in a planetary mixer and mixed for 5 to 20 minutes. Binder solution (polyvinylpyrrolidone K-30(17mg) in purified water) is added to contents of planetary mixer and mixed to get dough mass. The dough mass was dried, and dried granules passed through #18. The blending of ingredients above dried granules, magnesium stearate(11.5mg), croscarmellose sodium(6mg), colloidal anhydrous silica(7mg) and sodium starch glycollate(19mg) in a blender and mix for 5 to 10 minutes. The final blend was compressed into 700mg tablets using compression machine.

Claims

We claim: 1. A pharmaceutical formulation comprising in parts by weight from about 25% to about 35% zidovudine, from about 15% to 25% about nevirapine, from about 10% to about 20% lamivudine, from about 10% to about 30% microcrystalline cellulose, from about 2.5% to about 10% starch, from about 1.0% to about 2.5% croscarmellose sodium, from about 1.0% to about 2.0% polyvinylpyrrolidone K-30, from about 1.0% to about 2.0% magnesium stearate, from about 0.5% to about 1.5% colloidal anhydrous silica, from about 1.5% to about 3% crospovidone, from about 1.75% to about 2.5% opadry white. 2. The formulation as claimed in claim 1 in the form of a tablet, a caplet, a pellet, a capsule, a granule, a pil, a powder or a sachet. 3. The formulation as claimed in claim 2 in the form of a tablet. 4. The formulation as claimed in claim 3, wherein the tablet-containing amount of zidovudine is 300 mg, nevirapine is 200 mg and lamivudine is 150 mg. 5. The formulation as claimed in claim 2, wherein the capsule contains a powder, a compressed powder or a granule. 6. The formulation as claimed in claim 1 , wherein the amount of zidovudine is about 28% to about 33%, lamivudine is about 14% to about 17%, nevirapine is about 18% to about 22%, microcrystalline cellulose is about 17% to about 20%, starch is about 6% to about 7.5%, croscarmellose sodium is about 1.5% to about 2%, polyvinylpyrrolidone K-30 is about 1.5% to about 2%, magnesium stearate is about 1.25% to about 1.75%, colloidal anhydrous silica is about 0.75% to about 1%, crospovidone is about 1.5% to about 2% and opadry white is 2%. 7. The formulation as claimed in claim 1 , wherein at least one additional excipient is used. 8. The formulation as claimed in claim 7, wherein the additional excipient is selected from pharmaceutical lubricants, disintegrators, binders, glidents and fillers; and a mixture thereof. 9. The formulation as claimed in claim 8, wherein the filler is selected from calcium carbonate, dibasic calcium phosphate, lactose, magnesium carbonate, magnesium oxide, lactose anhydrous, microcrystalline cellulose and mannitol; and a mixture thereof. 10. The formulation as claimed in claim 8, wherein the lubricant is selected from stearic acid, a salt of stearic acid, talc, sodium stearyl fumarate, glyceryl behenate, magnesium silicate, magnesium trisilicate and hydrogenated castor oil; and a mixture thereof. 1 1. The formulation as claimed in claim 8, wherein the disintegrator is selected from sodium starch glycolate, starch, croscarmellose sodium, crospovidone, carboxymethyl cellulose calcium, carboxymethyl cellulose sodium and magnesium aluminium silicate; and a mixture thereof. 12. The formulation as claimed in claim 8, wherein the glident is selected from colloidal anhydrous silica and talc; and a mixture thereof. 13. The formulation as claimed in claim 8, wherein the binder is selected from hydroxypropyl cellulose, polyvinylpyrrolidone k-30, hydroxypropyl cellulose(low-substituted) and starch; and a mixtures thereof. 14. The formulation as claimed in claim 7, wherein the excipient selection depends on various factors, such as, the choice of active ingredient percentage, the objectives of the tablet formulation development and method of manufacture. 15. A pharmaceutical formulation comprising in parts by weight from about 25% to about 35% lamivudine, from about 4% to about 10% stavudine, from about 10% to about 25% microcrystalline cellulose, from about 20% to about 35% lactose, from about 5% to about 15% starch, from about 0.5% to about 2.5% croscarmellose sodium, from about 0.1 % to about 0.6% lake sunset yellow or lake quinoline yellow, from about 0.5% to about 5% polyvinylpyrrolidone k-30, from about 1 % to about 3% magnesium stearate, from about 0.25% to about 2% colloidal anhydrous silica and from about 1.0% to about 3% sodium starch glycollate. 16. The formulation as claimed in claim 15 in the form of a tablet, a caplet, a pellet, a capsule, a granule, a pil, a powder or a sachet. 17. The formulation as claimed in claim 16 in the form of a tablet. 18. The formulation as claimed in claim 17, wherein the tablet-containing amount of lamivudine is 150 mg and stavudine is 30 mg. 19. The formulation as claimed in claim 17, wherein the tablet-containing amount of lamivudine is 150 mg and stavudine is 40 mg. 20. The formulation as claimed in claim 16, wherein the capsule contains a powder, a compressed powder or a granule. 21. The formulation as claimed in claim 15, wherein the amount of lamivudine is about 28% to about 32%, stavudine is about 5.5% to about 6.5%, microcrystalline cellulose is about 14% to about 18%, lactose is about 26% to about 31%, starch is about 9% to about 11%, croscarmellose sodium is about 1.5% to about 2%, lake sun set yellow is about 0.3% to about 0.5%, polyvinylpyrrolidone K-30 is about 1.5% to about 2.5%, magnesium stearate is about 1.5% to about 2.5%, colloidal anhydrous silica is about 0.5% to abouti .0% and sodium starch glycol late is about 2.25 to about 3.0%. 22. The formulation as claimed in claim 15, wherein the amount of lamivudine is about 28% to about 32%, stavudine is about 7% to about 9%, microcrystalline cellulose is about 14% to about 17%, lactose is about 25% to about 30%, starch is about 9% to about 11%, croscarmellose sodium is about 1.5% to about 2%, lake Quinolline yellow is about 0.3% to about 0.5%, polyvinylpyrrolidone K-30 is about 1.5% to about 2.5%, magnesium stearate is about 1.5% to about 2.5%, colloidal anhydrous silica is about 0.5% to 1% and sodium starch glycollate is about 2.25% to about 3.0%. 23. The formulation as claimed in claim 15, wherein at least one additional excipient is used. 24. The formulation as claimed in claim 23, wherein the additional excipient is selected from pharmaceutical lubricants, disintegrators, binders, glidents and fillers; and a mixture thereof. 25. The formulation as claimed in claim 24, wherein the filler is selected from calcium carbonate, dibasic calcium phosphate, lactose, magnesium carbonate, magnesium oxide, lactose anhydrous, microcrystalline cellulose and mannitol; and a mixture thereof. 26. The formulation as claimed in claim 24, wherein the lubricant is selected from stearic acid, a salt of stearic acid, talc, sodium stearyl fumarate, glyceryl behenate, magnesium silicate, magnesium trisilicate and hydrogenated castor oil; and a mixture thereof. 27. The formulation as claimed in claim 24, wherein the disintegrator is selected from sodium starch glycolate, starch, croscarmellose sodium, crospovidone, carboxy methyl cellulose calcium, carboxymethyl cellulose sodium and magnesium aluminium silicate; and a mixture thereof. 28. The formulation as claimed in claim 24, wherein the glident is selected from colloidal anhydrous silica and talc; and a mixture thereof. 29. The formulation as claimed in claim 24, wherein the binder is selected from hydroxypropyl cellulose, polyvinylpyrrolidone k-30, hydroxypropyl cellulose(low-substituted) and starch; and a mixtures thereof. 30. The formulation as claimed in claim 23, wherein the excipient selection depends on various factors, such as, the choice of active ingredient percentage, the objectives of the tablet formulation development and method of manufacture. 31. A pharmaceutical formulation comprising in parts by weight from about 20% to 35% nevirapine, from about 15% to about 25% lamivudine, from about 2% to about 8% stavudine, from about 23% to about 35% lactose, from about 5% to about 10% starch, from about 0.5% to about 4% croscarmellose sodium, from about 0.1% to about 0.4% lake sunset yellow or Lake Quinoline yellow, from about 1 % to about 3.5% polyvinylpyrrolidone k-30, from about 1 % to about 2.5% magnesium stearate, from about 0.5% to about 1.5% colloidal anhydrous silica and from about 1.0% to about 4% sodium starch glycollate. 32. The formulation as claimed in claim 31 in the form of a tablet, a caplet, a pellet, a capsule, a granule, a pil, a powder or a sachet. 33. The formulation as claimed in claim 32 in the form of a tablet. 34. The formulation as claimed in claim 33, wherein the tablet-containing amount of nevirapine is 200 mg, lamivudine is 150 mg and stavudine is 30 mg. 35. The formulation as claimed in claim 33, wherein the tablet-containing amount of nevirapine is 200 mg, lamivudine is 150 mg and stavudine is 40 mg. 36. The formulation as claimed in claim 32, wherein the capsule contains a powder, a compressed powder or a granule. 37. The formulation as claimed in claim 31 , wherein the amount of nevirapine is about 26% to about 31 %, lamivudine is about 19% to about 23%, stavudine is about 4% to about 4.5%, lactose is about 25% to about 30%, starch is about 7% to about 8.5 %, croscarmellose sodium is about 2% to about 2.5% %, lake sun set yellow is about 0.25% to 0.35%, polyvinylpyrrolidone K-30 is about 2% to about 3%, magnesium stearate is about 1.5% to about 2%, colloidal anhydrous silica is about 0.5% to 1.25% and sodium starch glycollate is about 2.5% to about 3%. 38. The formulation as claimed in claim 31 , wherein the amount of nevirapine is about 26% to about 31%, lamivudine is about 19% to about 23%, stavudine • is about 5% to about 6.5%, lactose is about 25% to about 32%, starch is about 7 to about 8.5%, croscarmellose sodium is about 1.5 to about 2.5%, lake quinoline yellow is about 0.25 to about 0.35%, polyvinylpyrrolidone K-30 is about 2% to about 3%, magnesium stearate is about 1.5% to about 2%, colloidal anhydrous silica is about 0.5 to about 1.25% and sodium starch glycollate is about 2.5% to 3%. 39. The formulation as claimed in claim 31 , wherein at least one additional excipient is used. 40. The formulation as claimed in claim 39, wherein the additional excipient is selected from pharmaceutical lubricants, disintegrators, binders, glidents and fillers; and a mixture thereof. 41. The formulation as claimed in claim 40, wherein the filler is selected from calcium carbonate, dibasic calcium phosphate, lactose, magnesium carbonate, magnesium oxide, lactose anhydrous, microcrystalline cellulose and mannitol; and a mixture thereof. 42. The formulation as claimed in claim 40, wherein the lubricant is selected from stearic acid, a salt of stearic acid, talc, sodium stearyl fumarate, glyceryl behenate, magnesium silicate, magnesium trisilicate and hydrogenated castor oil; and a mixture thereof. 43. The formulation as claimed in claim 40, wherein the disintegrator is selected from sodium starch glycolate, starch, croscarmellose sodium, crospovidone, carboxymethyl cellulose calcium, carboxymethyl cellulose sodium and magnesium aluminium silicate; and a mixture thereof. 44. The formulation as claimed in claim 40, wherein the glident is selected from colloidal anhydrous silica and talc; and a mixture thereof. 45. The formulation as claimed in claim 40, wherein the binder is selected from hydroxypropyl cellulose, polyvinylpyrrolidone k-30, hydroxypropyl cellulose(low-substituted) and starch; and a mixtures thereof. 6. The formulation as claimed in claim 39, wherein the excipient selection depends on various factors, such as, the choice of active ingredient percentage, the objectives of the tablet formulation development and method of manufacture.