Delayed release tablet of venlafaxin

• US 20030091634A1
• Filed: 09/13/2002
• Published: 05/15/2003
• Est. Priority Date: 09/14/2001
• Status: Abandoned Application

• Current Assignee: Biovail Laboratories International Srl (Bausch Health Cos., Inc.)
• Original Assignee: Biovail Laboratories International Srl (Bausch Health Cos., Inc.)
• Inventors: Seth, Pawan
• Application Number:
  US10/244,059
• Publication Number:
  US 20030091634A1
• Time in Patent Office: Days
• US Class Current: 424/468
• CPC Class Codes: A61K 9/2013 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/284 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone
• CPC Class Codes: A61K 9/2866 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose

Abstract

The invention provides a delayed release tablet, comprising: (i) a core comprising an active ingredient and a gelling agent; and (ii) a coating consisting essentially of a water-insoluble, water-permeable film-forming polymer, a plasticizer and a water-soluble polymer.

Claims

1. A delayed release tablet comprising:

(i) a core comprising 10 to 70% of active ingredient, 10 to 80% of a gelling agent, and optional conventional excipients; and

(ii) a coating consisting essentially by weight, based on the coating weight, of 20 to 85% of a water-insoluble, water-permeable film-forming polymer, of 10 to 75% of a water-soluble polymer or substance and 3 to 40% of a plasticizer.

2. The tablet of claim 1, where the water-insoluble, water-permeable film-forming polymer is ethylcellulose.

3. The tablet of claim 1, where the water-soluble polymer or substance is polyvinylpyrrolidone.

4. The tablet of claim 1, where the plasticizer is stearic acid or dibutyl sebacate.

5. The tablet of claim 1, where the water-insoluble, water-permeable film-forming polymer is ethylcellulose, the water-soluble polymer or substance is polyvinylpyrrolidone and the plasticizer is stearic acid or dibutyl sebacate.

6. The tablet of claim 1, where the weight proportions water-insoluble, water-permeable film-forming polymer/water-soluble polymer or substance/plasticizer are 50-85/10-40/5-20.

7. The tablet of claim 1, where the water-insoluble, water-permeable film-forming polymer is ethylcellulose, the water-soluble polymer or substance is polyvinylpyrrolidone and the plasticizer is stearic acid or dibutyl sebacate, and where the weight proportions water-insoluble, water-permeable film-forming polymer/ water-soluble polymer or substance/plasticizer are 50-85/10-40/5-20.

8. The tablet of claim 1, where the gelling agent is a mixture of at least two gelling agents.

9. The tablet of claim 1, where the gelling agent of the core is hydroxypropylmethylcellulose, xanthan gum, polyvinylpyrrolidone or a mixture thereof.

10. The tablet of claim 1, where the core further comprises a fusible substance, in an amount of 10 to 80%, of the core dry weight.

11. The tablet of claim 10, where the fusible substance is stearic acid or glyceryl behenate.

12. The tablet of claim 1, where the core comprises the active ingredient, hydroxypropylmethylcellulose and stearic acid or glyceryl behenate.

18. The tablet of claim 1, where the active ingredient is venlafaxin or venlafaxine hydrochloride salt.

28. The tablet of claim 18, exhibiting a dissolution profile such that after 2 hours, from 7 to 40% of the venlafaxin is released;

after 4 hours, from 15 to 70% of the venlafaxin is released;

after 8 hours, from 50 to 100% of the venlafaxin is released;

after 12 hours, more than 75% of the venlafaxin is released.

13. A delayed release tablet comprising:

(i) a core comprising 10 to 70% of active ingredient, 10 to 80% of a gelling agent, 10 to 80% of a fusible substance, and optional conventional excipients; and

(ii) a coating consisting essentially by weight, based on the coating weight, of 20 to 85% of a water-insoluble, water-permeable film-forming polymer, of 10 to 75% of a water-soluble polymer or substance and 3 to 40% of a plasticizer.

14. The tablet of claim 13, where the weight proportions active ingredient/gelling agent/fusible substance are 25-60/10-40/20-50.

15. The tablet of claim 13, where the gelling agent is hydroxypropylmethylcellulose and the fusible substance is stearic acid or glyceryl behenate.

16. The tablet of claim 13, where the weight proportions water-insoluble, water-permeable film-forming polymer/ water-soluble polymer or substance/plasticizer are 50-85/10-40/5-20.

17. The tablet of claim 13, where the water-insoluble, water-permeable film-forming polymer is ethylcellulose, the water-soluble polymer is polyvinylpyrrolidone and the plasticizer is stearic acid or dibutyl sebacate.

19. The tablet of claim 13, where the active ingredient is venlafaxin or venlafaxine hydrochloride salt.

29. The tablet of claim 19, exhibiting a dissolution profile such that after 2 hours, from 7 to 40% of the venlafaxin is released;

after 4 hours, from 15 to 70% of the venlafaxin is released;

after 8 hours, from 50 to 100% of the venlafaxin is released;

after 12 hours, more than 75% of the venlafaxin is released.

20. A delayed release tablet comprising:

(i) a core comprising 25 to 60% of venlafaxin or venlafaxine hydrochloride salt, 10 to 40% of a gelling agent, 20 to 50% of a fusible substance, and optional conventional excipients; and

(ii) a coating consisting essentially by weight, based on the coating weight, of 50 to 85% of a water-insoluble, water-permeable film-forming polymer, of 10 to 40% of a water-soluble polymer or substance and 5 to 20% of a plasticizer.

21. The tablet of claim 20, where the gelling agent is hydroxypropylmethylcellulose and the fusible substance is stearic acid or glyceryl behenate.

22. The tablet of claim 20, where the water-insoluble, water-permeable film-forming polymer is ethylcellulose, the water-soluble polymer is polyvinylpyrrolidone and the plasticizer is stearic acid or dibutyl sebacate.

30. The tablet of claim 20, exhibiting a dissolution profile such that after 2 hours, from 7 to 40% of the venlafaxin is released;

after 4 hours, from 15 to 70% of the venlafaxin is released;

after 8 hours, from 50 to 100% of the venlafaxin is released;

after 12 hours, more than 75% of the venlafaxin is released.

23. A delayed release tablet comprising:

(i) a core comprising 10 to 70% of venlafaxin or venlafaxine hydrochloride salt, 10 to 80% of a gelling agent, and optionally conventional excipients; and

(ii) a coating consisting essentially by weight, based on the coating weight, of 40 to 75% of a water-insoluble, water-permeable film-forming polymer, of 10 to 40% of a water-soluble polymer or substance and 10 to 40% of a plasticizer.

24. The tablet of claim 23, where the gelling agent is a mixture of at least two gelling agents.

25. The tablet of claim 23, where the gelling agent of the core is hydroxypropylmethylcellulose, xanthan gum, polyvinylpyrrolidone or a mixture thereof.

26. The tablet of claim 23, where the water-insoluble, water-permeable film-forming polymer is ethylcellulose, the water-soluble polymer is polyvinylpyrrolidone and the plasticizer is stearic acid or dibutyl sebacate.

27. The tablet of claim 23, where the conventional excipient is a lubricant.

31. The tablet of claim 23, exhibiting a dissolution profile such that after 2 hours, from 7 to 40% of the venlafaxin is released;

after 4 hours, from 15 to 70% of the venlafaxin is released;

after 8 hours, from 50 to 100% of the venlafaxin is released;

after 12 hours, more than 75% of the venlafaxin is released.

32. A process for preparing a tablet, said tablet comprising:

(i) a core comprising 10 to 70% of active ingredient, 10 to 80% of a gelling agent, 10 to 80% of a fusible substance, and optional conventional excipients; and

(ii) a coating consisting essentially by weight, based on the coating weight, of 20 to 85% of a water-insoluble, water-permeable film-forming polymer, of 10 to 75% of a water-soluble polymer or substance and 3 to 40% of a plasticizer;

where the process comprises the steps of;

(i) mixing the active ingredient and the fusible substance;

(ii) heating the obtained mixture so that the fusible substance is fused;

(iii) adding and mixing the gelling agent and the optional conventional excipients, whereby granules are obtained;

(iv) compressing said granules into tablet cores; and

(v) coating said tablet cores.

33. The process of claim 32, in which step (v) comprises the sub-steps of:

(a) dissolving the water-insoluble, water-permeable film-forming polymer, the water-soluble polymer or substance and the plasticizer into a solvent; and

(b) spraying the thus-obtained solution onto the tablet cores.

34. A process for preparing a tablet, said tablet comprising:

(i) a core comprising 10 to 70% of active ingredient, 10 to 80% of at least two gelling agents, and optionally conventional excipients; and

(ii) a coating consisting essentially by weight, based on the coating weight, of 40 to 75% of a water-insoluble, water-permeable film-forming polymer, of 10 to 40% of a water-soluble polymer or substance and 10 to 40% of a plasticizer;

where the process comprises the steps of;

i) mixing and drying the active ingredient with a first gelling agent of said at least two gelling agents,

ii) granulating the obtained mixture with a solution of a second gelling agent of said at least two gelling agents,

iii) compressing said granules into tablet cores optionally with conventional excipients; and

iv) coating said tablet cores.

35. The process of claim 34 in which the solution in step ii) is an alcoholic solution of the second gelling agent.

36. The process of claim 34, in which step (iv) comprises the sub-steps of:

(a) dissolving the water-insoluble, water-permeable film-forming polymer, the water-soluble polymer or substance and the plasticizer into a solvent; and

(b) spraying the thus-obtained solution onto the tablet cores.