Pharmaceutical composition containing irbesartan

• US 20050271720A1
• Filed: 06/02/2005
• Published: 12/08/2005
• Est. Priority Date: 06/04/2004
• Status: Active Grant

• Current Assignee: Teva Pharmaceuticals USA, Inc. (Teva Pharmaceutical Industries Limited)
• Original Assignee: Teva Pharmaceutical Industries Limited
• Inventors: Kolatkar, Gershon, Zisman, Erela
• Granted Patent: US 8,226,977 B2
• Time in Patent Office: Days
• US Class Current: 424/464
• 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 greater than 70% w/w irbesartan and at least one pharmaceutically-acceptable excipient.

2. The composition of claim 1, 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.

5. The composition of claim 1, in the form of a tablet.

6. The composition of claim 1, wherein said composition comprises a binder.

7. The composition of claim 6, wherein a binder is povidone or pregelatinized starch.

8. The composition of claim 7, wherein a binder is povidone.

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

10. The composition of claim 9, wherein a binder is pregelatinized starch (starch 1500).

11. The composition of claim 10, wherein the pregelatinized starch (starch 1500) is from about 1.0 to about 10.0% w/w of the composition.

12. The composition of claim 1, wherein said composition comprises a disintegrant.

13. The composition of claim 12, wherein a disintegrant is croscarmellose sodium.

14. The composition of claim 13, wherein the croscarmellose sodium is Ac-Di-Sol and is from about 1.0 to about 7.0% w/w of the composition.

15. The composition of claim 1, wherein said composition comprises a surfactant.

16. The composition of claim 15, wherein a surfactant is poloxamer 188.

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

18. The composition of claim 1, wherein said composition comprises a diluent.

19. The composition of claim 18, wherein said diluent is microcrystalline cellulose.

20. The composition of claim 19, wherein the microcrystalline cellulose is Avicel PH 102 FMC and comprises from about 2.0 to about 10.0% w/w of the composition.

21. The composition of claim 1, wherein said composition comprises an antiadherent.

22. The composition of claim 21, wherein the antiadherent is silicon dioxide.

23. The composition of claim 22, wherein the silicon dioxide is syloid 244 and comprises from about 0.4% w/w to about 0.5% w/w of the composition.

24. The composition of claim 1, wherein said composition comprises a lubricant.

25. The composition of claim 24, wherein said lubricant is magnesium stearate.

26. The composition of claim 25, wherein the magnesium stearate comprises from about 0.2 to about 2.0% w/w of the composition.

27. The composition of claim 1, further wherein said composition comprises at least one additoinal active pharmaceutical agent.

28. The composition of claim 27, wherein an additional active pharmaceutical agent is a diuretic agent.

29. The composition of claim 27, wherein an additional active agent is hydrochlorothiazide.

30. The composition of claim 1, wherein the composition comprises, by weight, 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 pregelantinized 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.

31. The composition of claim 30, wherein said composition is a tablet, and the tablet has 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.

32. The composition of claim 1, wherein the composition comprises, by weight, 79.79% irbesartan, and the pharmaceutical excipients comprise, 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 pregelantinized 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.

33. The composition of claim 32, wherein said composition is a tablet, such that the tablet has 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. The tablet of claim 9, wherein the tablet is prepared by a wet granulation method.

34. The composition of claim 1, which exhibits a dissolution profile according to which greater than about 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.

35. The composition of claim 1, which exhibits a dissolution profile according to which greater than about 85% 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.

36. The composition of claim 1, which exhibits a dissolution profile according to which at least about 75% of the irbesartan is dissolved within about 5 minutes, at least about 85% of the irbesartan is dissolved within about 10 minutes, and at least 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.

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

wherein said binder consists of pregelantinized starch and povidone;

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

38. The composition of claim 36, wherein the composition comprises, by weight, 79.79% irbesartan, 2.13% povidone, 6.38% pregelatinized starch, 3.15% croscarmellose sodium, 1.01% poloxamer 188, 5.96% microcrystalline cellulose, 1.01% magnesium stearate and 0.43% silicon dioxide.

39. The composition of claim 37, wherein the composition comprises 150 mg of irbesartan and 12.5 mg of hydrochlorothiazide.

40. The composition of claim 37, wherein the composition comprises, by weight, about 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.

3. A composition comprising greater than 70% w/w irbesartan, wherein said composition 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 L of 0.1N hydrochloric acid at 37°

C. with paddle speed of 50 rpm.

4. The composition of claim 3, which comprises greater than 75% w/w irbesartan and at least one pharmaceutically acceptable excipient.