CONTROLLED-RELEASE PHARMACEUTICAL TABLETS

• US 20080026060A1
• Filed: 07/25/2007
• Published: 01/31/2008
• Est. Priority Date: 07/25/2006
• Status: Active Grant

• Current Assignee: IntelGenx Corporation
• Original Assignee: IntelGenx Corporation
• Inventors: Paiement, Nadine, Zerbe, Horst G.
• Granted Patent: US 8,703,191 B2
• Time in Patent Office: Days
• US Class Current: 424/470
• CPC Class Codes: A61K 31/13 Amines A61K31/04 takes precedence
• CPC Class Codes: A61K 31/135 having aromatic rings , e.g. ketamine, nortriptyline methadone A61K31/137
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/2077 Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
• CPC Class Codes: A61K 9/2846 Poly(meth)acrylates

Abstract

Controlled-release tablets exhibiting excellent storage stability are achieved by granulating a pharmaceutically active agent with a hydroxyalkylcelluose, blending the resulting granules with an extragranular phase composed of a particulate material that provides a sustained-release matrix, and compressing the blend into a tablet form, which may be optionally coated, such as with an enteric coating composition, to provide delayed release and/or to enhance stability of the active agent.

Claims

1. A controlled-release pharmaceutical tablet comprising:

a granular phase comprising a pharmaceutically active agent, and a hydroxyalkylcellulose; and

an extragranular phase comprised of a particulate material that provides a sustained-release matrix, the granular phase being dispersed within the extragranular phase.

2. The tablet of claim 1, in which the hydroxyalkylcellulose is hydroxypropylcellulose.

3. The tablet of claim 1, in which the granular phase comprises 30% to 70% of the combined weight of the granular phase and the extragranular phase.

4. The tablet of claim 1, in which the pharmaceutically active agent comprises from 70% to 90% of the weight of the granular phase.

5. The tablet of claim 1, further comprising a second granular phase comprising a second pharmaceutically active compound and a hydroxyalkylcellulose.

6. The tablet of claim 5, wherein the second pharmaceutically active compound is mecamylamine.

7. The tablet of claim 1, wherein the pharmaceutically active agent is bupropion and which includes a bupropion stabilizer.

8. The tablet of claim 7, wherein the bupropion stabilizer is hydrochloric acid.

9. The tablet of claim 1, wherein the extragranular phase comprises a water-swellable and/or water-erodible polymer capable of forming a sustained-release matrix.

10. The tablet of claim 1, wherein the extragranular phase comprises a polymer or blend of polymers selected from polyvinylacetate, polyvinylpyrrolidone, and copolymers of vinylacetate and vinylpyrrolidone.

11. The tablet of claim 10, wherein the extragranular phase further comprises a polyethylene oxide.

12. The tablet of claim 1, further comprising an enteric coating.

13. The tablet of claim 1, in which the extragranular phase comprises a blend of polyvinylpyrrolidone, poly(vinylacetate), and polyethylene oxide.

14. The tablet of claim 1, in which the extragranular phase comprises a copolymer of vinylpyrrolidone and vinylacetate.

15. The tablet of claim 14, wherein the extragranular phase further comprises a polyethylene oxide.

16. The tablet of claim 1, wherein the extragranular phase includes stearic acid in an amount that is effective to provide lubrication during tableting.

17. A combination controlled-release bupropion, controlled-release mecamylamine pharmaceutical tablet comprising:

a granular phase comprising bupropion, a hydroxyalkylcellulose, and an optional pharmaceutically acceptable bupropion stabilizer;

a pharmaceutically effective amount of mecamylamine; and

an extragranular phase comprised of a particulate material that provides a sustained-release matrix, the granular phase and the mecamylamine being distributed within the extragranular phase.

18. The tablet of claim 17, in which the mecamylamine is present in a granulation comprising mecamylamine and a hydroxyalkylcellulose.

19. A stabilized bupropion tablet comprising:

a compressed core containing a therapeutically effective amount of bupropion; and

an enteric coating on the core, the enteric coating having a weight on a dry basis equal to at least 6% of the weight of the compressed core.

20. The stabilized tablet of claim 19, wherein the enteric coating has a weight on a dry basis equal to at least 10% of the weight of the compressed core.

21. The stabilized tablet of claim 19, wherein the core comprises a granular phase containing bupropion, and a hydroxyalkylcellulose, and an extragranular phase comprising a particulate material that provides a sustained release matrix in which the granular phase is distributed.

22. The stabilized tablet of claim 21, in which the hydroxyalkylcellulose is hydroxypropylcellulose.