EXTENDED RELEASE PELLET FORMULATION CONTAINING PRAMIPEXOLE OR A PHARMACEUTICALLY ACCEPTABLE SALT THEREOF

• US 20100086589A1
• Filed: 12/03/2009
• Published: 04/08/2010
• Est. Priority Date: 08/13/2004
• Status: Active Grant

• Current Assignee: Rolf-Stefan Brickl, Thomas Friedl
• Original Assignee: Rolf-Stefan Brickl, Thomas Friedl
• Inventors: Brickl, Rolf-Stefan, FRIEDL, Thomas
• Granted Patent: US 8,715,728 B2
• Time in Patent Office: Days
• US Class Current: 424/461
• CPC Class Codes: A61K 9/5078 with drug-free core
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs

Abstract

An extended release pellet comprising an active ingredient selected from pramipexole and the pharmaceutically acceptable salts thereof, and at least one release-modifying excipient.

Claims

1. An extended release pellet comprising pramipexole or a pharmaceutically acceptable salt thereof, and at least one release-modifying excipient.

2. The extended release pellet according to claim 1, wherein the pramipexole or the pharmaceutically acceptable salt thereof is embedded within a matrix formed by at least one release-modifying excipient.

3. The extended release pellet according to claim 1, wherein at least one of the release-modifying excipients is a lipid, wax, or water-insoluble polymer.

4. The extended release pellet according to claim 1, comprising a core and a coating, wherein at least one release-modifying excipient is incorporated in the coating.

5. The extended release pellet according to claim 4, wherein the pramipexole or the pharmaceutically acceptable salt thereof is incorporated in the core.

6. The extended release pellet according to claim 4, wherein the coating comprises at least a first layer and a second layer surrounding the first layer, wherein the first layer comprises the pramipexole or the pharmaceutically acceptable salt thereof, and wherein the second layer comprises at least one release-modifying excipient.

7. The extended release pellet according to claim 6, wherein at least one release-modifying excipient is ethyl cellulose, cellulose acetate, polyvinylacetate, polyacrylate, polymethacrylate, or ammonio methacrylate copolymer.

8. The extended release pellet according to claim 7, wherein the second layer further comprises at least one water-soluble excipient.

9. The extended release pellet according to claim 8, wherein at least one water-soluble excipient is hydroxypropyl cellulose, hydroxypropyl methyl cellulose, polyvinylpyrrolidone, and polyethylene glycol.

10. The extended release pellet according to claim 7, wherein the second layer further comprises an enteric coating polymer.

11. The extended release pellet according to claim 8, wherein enteric coating polymer is methacrylic acid copolymers type A and B.

12. The extended release pellet according to claim 10, wherein the second layer comprises from about 10 to about 85 wt.-% of the enteric coating polymer and from about 15 to about 75 wt.-% of the water-insoluble polymer.

13. The extended release pellet according to claim 6, wherein the core comprises a saccharide.

14. The extended release pellet according to claim 13, wherein the saccharide is saccharose, starch, cellulose, or a cellulose derivative.

15. The extended release pellet according to claim 14, wherein the saccharide is microcrystalline cellulose.

36. A capsule containing extended release pellets according to claim 1.

38. The capsule according to claim 36, wherein the capsule contains an amount of extended release pellets sufficient to provide an effective daily dose of pramipexole or a pharmaceutically acceptable salt thereof.

16. An extended release pellet comprising:

(1) an inert pellet core;

(2) a first layer comprising pramipexole or a pharmaceutically acceptable salt thereof; and

(3) a second layer provided on the first layer, the second layer being an extended release coating comprising;

(a) at least one water-insoluble polymer and optionally a pore former, the resulting pellet having a pH-independent in vitro release characteristic, or

(b) a mixture of a pH-dependent enteric-coating polymer and a pH-independently water swelling polymer,

wherein the extended release pellet has a close to zero order in vitro release characteristic at acidic pH values up to pH 6.8, an accelerated release above pH 6.8, and a more accelerated release above pH 7.3.

17. The extended release pellet according to claim 16, wherein the first layer further comprises one or more wet binders and further excipients.

18. The extended release pellet according to claim 16, wherein the inert pellet core comprises polysaccharides, cellulose, a cellulose derivative, starch, and/or waxes.

19. The extended release pellet according to claim 16, wherein the inert pellet core comprises saccharose and/or microcrystalline cellulose.

20. The extended release pellet according to claim 16, wherein the water-insoluble polymer is ethyl cellulose, cellulose acetate, polyvinylacetate, or polyacrylates and derivatives thereof.

21. The extended release pellet according to claim 16, wherein the pH-dependent enteric-coating polymer is an anionic carboxylic acrylic polymer soluble above a pH value of 5.5.

22. The extended release pellet according to claim 21, wherein the pH-dependent enteric-coating polymer is soluble above a pH value of 7.0.

23. The extended release pellet according to claim 21, wherein the pH-dependent enteric-coating polymer is a partly methyl esterified methacrylic acid polymer.

24. The extended release pellet according to claim 16, wherein the pH-independently water swelling polymer is a quaternary ammonium substituted acrylic polymer.

25. The extended release pellet according to claim 24, wherein the quaternary ammonium substituted acrylic polymer has an ammonium substitution of about 5 to about 10 percent by weight.

26. The extended release pellet according to claim 16, wherein the pH-dependent enteric-coating polymer is present in an amount of 10 to 85% by weight of the coating and the pH-independently water swelling polymer is present in an amount of 15 to 75% by weight of the coating.

27. The extended release pellet according to claim 21, wherein the pH-dependent enteric-coating polymer is present in an amount of 10 to 85% by weight of the coating and the pH-independently water swelling polymer is present in an amount of 15 to 75% by weight of the coating.

28. The extended release pellet according to claim 24, wherein the pH-dependent enteric-coating polymer is present in an amount of 10 to 85% by weight of the coating and the pH-independently water swelling polymer is present in an amount of 15 to 75% by weight of the coating.

29. The extended release pellet according to claim 16, comprising:

(1) an inert pellet core;

(2) a first layer comprising pramipexole or a pharmaceutically acceptable salt thereof; and

(3) a second layer provided on the first layer, the second layer being an extended release coating comprising a mixture of;

(i) a pH-dependent enteric-coating polymer,

(ii) a pH-independently water swelling polymer, and

(iii) a pore-forming component,

wherein the extended release pellet has a close to zero order in vitro release characteristic at acidic pH values up to pH 6.8, an accelerated release above pH 6.8, and a more accelerated release above pH 7.3.

30. The extended release pellet according to claim 29, wherein the pore-forming component is hydroxypropyl cellulose, hydroxypropyl methyl cellulose, polyvinylpyrrolidone, or polyethylene glycol.

37. A capsule containing extended release pellets according to claim 16.

39. The capsule according to claim 37, wherein the capsule contains an amount of extended release pellets sufficient to provide an effective daily dose of pramipexole or a pharmaceutically acceptable salt thereof.

31. An extended release pellet comprising pramipexole or a pharmaceutically acceptable salt thereof prepared by wet or melt extrusion or melt granulation using excipients achieving extended release without a further diffusion membrane.

32. A method of manufacturing extended release pellets, the method comprising the steps of:

(1) providing an inert starter pellet core;

(2) applying a solution or dispersion of a first coating composition comprising pramipexole or a pharmaceutically acceptable salt thereof, at least a binder, and optionally excipient(s) onto the inert starter pellet core, wherein the pramipexole or a pharmaceutically acceptable salt thereof is used as unmilled material dissolved/dispersed in a solvent together with the binder(s) and optional excipient(s), and subsequently drying the first coated pellet;

(3) applying a solution or dispersion of a second coating composition as functional coating composition onto the first coated pellet obtained in step (2), wherein the coating composition comprises (a) at least one water-insoluble polymer and optionally a pore former or (b) a mixture of a pH-dependent enteric-coating polymer and a pH-independently water swelling polymer, and optional excipient(s), and a solvent, and subsequently drying the obtained extended release pellet.

33. The method according to claim 32, further comprising performing manual screening after step (2) and/or step (3) in order to remove agglomerates.

34. The method according to claim 32, wherein the applying the first coating composition of step (2) is done by spraying the solution or dispersion of the first coating composition onto the inert starter pellet core.

35. The method according to claim 32, wherein the applying the second coating composition of step (3) is done by spraying the solution or dispersion of the second coating composition onto the first coated pellet.