Pharmaceutical composition containing irbesartan

• US 20120238555A1
• Filed: 05/31/2012
• Published: 09/20/2012
• Est. Priority Date: 06/04/2004
• Status: Active Grant

• Current Assignee: Teva Pharmaceuticals USA, Inc. (Teva Pharmaceutical Industries Limited)
• Original Assignee: Teva Pharmaceuticals USA, Inc. (Teva Pharmaceutical Industries Limited)
• Inventors: Kolatkar, Gershon, Zisman, Erela
• Granted Patent: US 8,414,920 B2
• Time in Patent Office: Days
• US Class Current: 514/223.5
• CPC Class Codes: A61K 31/4184 condensed with carbocyclic rings, e.g. benzimidazoles
• CPC Class Codes: A61K 31/54 having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
• CPC Class Codes: A61K 9/2027 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/2031 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/2059 Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/10 Antioedematous agents; Diuretics
• CPC Class Codes: A61P 9/12 Antihypertensives

Abstract

This invention relates to pharmaceutical compositions containing irbesartan, providing oral formulations with a high relative amount or concentration of irbesartan. In one embodiment, the present invention provides an oral formulation of irbesartan containing greater than 70% w/w irbesartan. In another embodiment, the invention provides an oral formulation of irbesartan which exhibits a dissolution profile according to which greater than about 85% of the Irbesartan is dissolved within about 30 minutes using USP apparatus 2, placing the tablet in 1000 mL of 0.1N hydrochloric acid at 37° C. with paddle speed of 50 rpm. The formulation can optionally contain at least one additional active ingredient.

Claims

1. A composition comprising irbesartan, a binder, and a surfactant, wherein the irbesartan is greater than 70% w/w of the composition.

2. A composition comprising irbesartan, a binder, and a surfactant, wherein the irbesartan is at least 75% w/w of the composition.

3. The composition of claim 2, wherein said composition exhibits a dissolution profile according to which greater than 85% of the irbesartan is dissolved within about 30 minutes using United States Pharmacopeia (USP) apparatus 2, placing the tablet in 1000 mL of 0.1N hydrochloric acid at 37°

C. with paddle speed of 50 rpm.

4. The composition of claim 2, wherein said composition further comprises at least one diuretic agent.

5. The composition of claim 4, wherein the diuretic agent is hydrochlorothiazide.

6. The composition of claim 2, wherein the composition is in the form of a tablet.

7. The composition of claim 2, wherein the composition is in the form of the product of a wet granulation process.

8. The composition of claim 2, wherein the binder is povidone or pregelatinized starch.

9. The composition of claim 8, wherein the povidone is about 1.0% w/w to about 7.0% w/w of the composition.

10. The composition of claim 8, wherein the pregelatinized starch is about 1.0% w/w to about 10.0% w/w of the composition.

11. The composition of claim 2, wherein said composition further comprises at least one of:

a disintegrant, a diluent, an antiadherent, and a lubricant.

12. The composition of claim 11, wherein the disintegrant is croscarmellose sodium, the diluent is microcrystalline cellulose, the antiadherent is silicon dioxide, and the lubricant is magnesium stearate.

13. The composition of claim 12, wherein the croscarmellose sodium is about 1.0% w/w to about 7.0% w/w of the composition.

14. The composition of claim 2, wherein the surfactant is a polyethylene-polypropylene glycol co-polymer.

15. The composition of claim 14, wherein the polyethylene-polypropylene glycol co-polymer is about 0.2% w/w to about 6.0% w/w of the composition.

16. The composition of claim 2, wherein the surfactant is poloxamer 188.

17. The composition of claim 16, wherein the poloxamer 188 is about 0.2% w/w to about 6.0% w/w of the composition.

18. The composition of claim 12, wherein the microcrystalline cellulose is about 2.0% w/w to about 10.0% w/w of the composition.

19. The composition of claim 12, wherein the silicon dioxide is about 0.4% w/w to about 0.5% w/w of the composition.

20. The composition of claim 12, wherein the magnesium stearate is about 0.2% w/w to about 2.0% w/w of the composition.

21. The composition of claim 2, wherein the composition comprises, by weight, about 75% irbesartan, and by weight, about 10% binder, about 7.5% diluent, about 4% disintegrant, about 2% surfactant, about 1% lubricant, and about 0.5% antiadherent;

wherein said binder consists of pregelatinized starch and povidone;

said diluent is microcrystalline cellulose, said disintegrant is croscarmellose sodium, said surfactant is poloxamer 188, said lubricant is magnesium stearate, and said antiadherent is silicon dioxide.

22. The composition of claim 21, wherein said composition is a tablet, and the tablet exhibits a dissolution such that greater than 85% of the irbesartan contained therein dissolves within 30 minutes under the following conditions:

USP apparatus 2, placing the tablet in 1000 mL of 0.1N hydrochloric acid at 37°

C. with paddle speed of 50 rpm.

23. The composition of claim 2, wherein the composition comprises, by weight, 79.79% irbesartan, and, by weight, about 8.5% binder, about 5.9% diluent, about 3.1% disintegrant, about 1% surfactant, about 1% lubricant, and about 0.5% antiadherent;

wherein said binder consists of pregelatinized starch and povidone;

said diluent is microcrystalline cellulose, said disintegrant is croscarmellose sodium, said surfactant is poloxamer 188, said lubricant is magnesium stearate, and said antiadherent is silicon dioxide.

24. The composition of claim 23, wherein said composition is a tablet, such that the tablet exhibits a dissolution performance such that greater than 85% of the irbesartan contained therein dissolves within 30 minutes under the following conditions:

USP apparatus 2, placing the tablet in 1000 mL of 0.1N hydrochloric acid at 37°

C. with paddle speed of 50 rpm.

25. The composition of claim 2, wherein the composition comprises, by weight, 79.79% irbesartan, about 3% to about 7% hydrochlorothiazide, about 5.3% to about 7.5% binder, about 3.5% to about 6% diluent, about 3% to about 3.2% disintegrant, about 1% to about 1.1% lubricant, and about 0.4% to about 0.5% antiadherent;

wherein said binder consists of pregelatinized starch and povidone;

said diluent is microcrystalline cellulose, said disintegrant is croscarmellose sodium, said lubricant is magnesium stearate, said surfactant is poloxamer 188, and said antiadherent is silicon dioxide.

26. The composition of claim 2, wherein the composition comprises, by weight, about 79.79% irbesartan, about 2.13% povidone, about 6.38% pregelatinized starch, about 3.15% croscarmellose sodium, about 1.01% poloxamer 188, about 5.96% microcrystalline cellulose, about 1.01% magnesium stearate and about 0.43% silicon dioxide.

27. The composition of claim 2, wherein the composition comprises, by weight, about 79.79% irbesartan, about 3.3% hydrochlorothiazide, about 3.1% pregelatinized starch, about 2.1% povidone, about 5.3% microcrystalline cellulose, about 4.7% croscarmellose sodium, about 0.4% silicon dioxide and about 1% magnesium stearate.

28. The composition of claim 2, wherein said composition is a tablet, such that the tablet exhibits a dissolution profile according to which greater than 80% of the irbesartan is dissolved within about 10 minutes using USP apparatus 2, placing the tablet in 1000 mL of 0.1N hydrochloric acid at 37°

C. with paddle speed of 50 rpm.

29. The composition of claim 2, wherein said composition is a tablet, such that the tablet exhibits a dissolution profile according to which about 75% of the irbesartan is dissolved within about 5 minutes, about 85% of the irbesartan is dissolved within about 10 minutes, and about 95% of the irbesartan is dissolved within about 20 minutes using USP apparatus 2, placing the tablet in 1000 mL of 0.1N hydrochloric acid at 37°

C. with paddle speed of 50 rpm.