Controlled-release pharmaceutical tablets

• US 8,703,191 B2
• Filed: 07/25/2007
• Issued: 04/22/2014
• Est. Priority Date: 07/25/2006
• Status: Active Grant

• Current Assignee: IntelGenx Corporation
• Original Assignee: IntelGenx Corporation
• Inventors: Zerbe, Horst G., Paiement, Nadine
• Primary Examiner(s): ROGERS, JAMES WILLIAM
• Application Number:
  US11/782,838
• Publication Number:
  US 20080026060A1
• Time in Patent Office: 2,463 Days
• Field of Search: None
• US Class Current: 424/468
• 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 first granular phase including bupropion, an acidic stabilizing agent in an amount less than 1% of the weight of the first granular phase, and hydroxypropylcellulose in an amount of from about 10% to about 30% of the weight of the first granular phase;

a second granular phase comprising mecamylamine and a hydroxyalkylcellulose; and

an extragranular phase that provides a sustained-release matrix, the first and second granular phases are dispersed in the extragranular phase, the extragranular phase comprising a particulate material that provides a diffusion barrier, controlled erosion, or a diffusion barrier and controlled erosion, wherein the extragranular phase includes polyalkylene oxide and a water-swellable or water-erodible polymer selected from the group consisting of polyvinyl pyrrolidone, poly(vinylacetate), copolymers of vinylpyrrolidone and vinylacetate, and blends thereof, the extragranular phase comprising polyalkylene oxide in an amount that is effective to adjust hydrophilicity of the sustained-release matrix and thereby adjust the rate of sustained release;

wherein the first granular phase comprises about 30% to about 70% of the combined weight of the first granular phase and the extragranular phase.

2. The tablet of claim 1, in which bupropion comprises from 70% to 90% of the weight of the first granular phase.

3. The tablet of claim 1, wherein the acidic stabilizing agent is hydrochloric acid.

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

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

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

7. The tablet of claim 6, wherein the polyalkylene oxide is polyethylene oxide.

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

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

a granular phase comprising bupropion, hydroxypropylcellulose in an amount of from about 10% to about 30% of the weight of the granular phase;

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 dispersed within the extragranular phase, the extragranular phase comprising a particulate material that provides a diffusion barrier, controlled erosion, or a diffusion barrier and controlled erosion, wherein the extragranular phase includes polyalkylene oxide and a water-swellable or water-erodible polymer selected from the group consisting of polyinyl pyrrolidone, poly(vinylacetate), copolymers of vinylpyrrolidone and vinylacetate, and blends thereof, the extragranular phase comprising polyalkylene oxide in an amount that is effective to adjust hydrophilicity of the sustained-release matrix and thereby adjust the rate of sustained-release, and wherein the granular phase comprises about 30% to about 70% of the combined weight of the granular phase and the extragranular phase.

10. The tablet of claim 9, in which the granular phase further comprises a pharmaceutically acceptable bupropion stabilizer.