Oral dosage forms

• US 20080014257A1
• Filed: 07/14/2006
• Published: 01/17/2008
• Est. Priority Date: 07/14/2006
• Status: Abandoned Application

• Current Assignee: Par Pharmaceutical, Inc. (Endo International PLC)
• Original Assignee: Par Pharmaceutical, Inc. (Endo International PLC)
• Inventors: He, Ping, Sanghvi, Suketu, Patel, Damodar, Femia, Robert
• Application Number:
  US11/486,375
• Publication Number:
  US 20080014257A1
• Time in Patent Office: Days
• US Class Current: 424/457
• CPC Class Codes: A61K 31/4439 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole nicotine A61K31/465
• CPC Class Codes: A61K 31/65 Tetracyclines
• CPC Class Codes: A61K 9/2009 Inorganic compounds
• 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 9/2059 Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
• CPC Class Codes: A61K 9/2866 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/4808 characterised by the form of the capsule or the structure of the filling; Capsules containing small tablets; Capsules with outer layer for immediate drug release capsules filled with granules or microparticles A61K9/16; filled with microcapsules or coated microparticles A61K9/50; with mixture of different granules, microcapsules, (coated) microparticles A61K9/5084
• CPC Class Codes: A61K 9/4858 Organic compounds
• CPC Class Codes: A61K 9/4866 Organic macromolecular compounds

Abstract

This invention relates to an oral dosage form of a pharmaceutically active ingredient comprising: (a) an outer capsule and (b) non-uniform pellets, having a non-uniform shape and/or size, contained within the capsule, wherein the pellets comprise a compressed powder comprising a pharmaceutically active ingredient. In one embodiment the active ingredient is selected from the group consisting of doxycycline, omeprazole, esomeprazole, and propafenone. Pharmaceutical formulations of the active ingredients as well as methods and tools for making the oral dosage form are also described.

Claims

1. An oral dosage form of a pharmaceutically active ingredient comprising:

(a) an outer capsule; and

(b) non-uniform pellets, having a non-uniform shape and/or size, comprised within the capsule,

wherein the pellets comprise a compressed powder comprising a pharmaceutically active ingredient.

2. The oral dosage form of claim 1, wherein the active ingredient is selected from the group consisting of doxycycline, omeprazole, esomeprazole, and propafenone.

3. The oral dosage form of claim 1, wherein the non-uniform pellets have a diameter of from about 1 mm to about 3 mm.

4. The oral dosage form of claim 1, wherein the non-uniform pellets have a maximum and a minimum diameter, each of which is independently from about 1 mm to about 3 mm.

5. The oral dosage form of claim 1, wherein the non-uniform pellets are primarily spherical, cubic, cylindrical, irregular, or a combination thereof.

6. The oral dosage form of claim 1, wherein the non-uniform pellets are coated with a pharmaceutically acceptable coating material.

7. The oral dosage form of claim 6, wherein the coating material comprises Opadry colors.

8. The oral dosage form of claim 7, wherein the coating material comprises a material selected from a pH-dependent polymer and a pH-independent polymer.

9. The oral dosage form of claim 8, wherein the pH-dependent polymer is selected from the group consisting of methacrylic acid/methyl methacrylate copolymers (Eudragit L 100, Eudragit S 100), methacrylic acid/ethyl acrylate copolymers (Eudragit L 30D 55), methacrylic acid/methyl acrylate and methyl methacrylate copolymers (Eudragit FS 30D), cellulose acetate phthalate, cellulose acetate trimellitate, hydroxypropyl methylcellulose acetate succinate, hydroxypropyl methylcellulose phthalate, povinyl acetate phthalate and shellac.

10. The oral dosage form of claim 8, wherein the pH-independent polymer is selected from the group consisting of ethylcellulose, methacrylic ester copolymers, and ammonio methacrylate copolymers.

11. The oral dosage form of claim 2, wherein the pellets are made by a process comprising:

(a) compressing a powder comprising the pharmaceutically active ingredient into compressed slugs; and

(b) breaking the slugs into non-uniform pellets, having a non-uniform shape and/or size.

12. The oral dosage form of claim 11, wherein the compressing step comprises roller compaction.

13. The oral dosage from of claim 11, wherein the process further comprises, subsequent to step (a) and prior to step (b), scoring at least one surface of the slugs.

14. The oral dosage from of claim 11, wherein the compressing step results in the formation of compressed slugs comprising scoring on at least one surface.

15. The oral dosage form of claim 14, wherein the depth of the scoring comprises up to about 95% of the thickness of the slugs.

16. The oral dosage form of claim 2, wherein the powder comprises:

(a) about 78.5 to about 79.5% by weight propafenone;

(b) about 4.5 to about 5.5% by weight povidone;

(c) about 4.5 to about 5.5% by weight ethyl cellulose;

(d) about 9.5 to about 10.5% by weight lactose anhydrous, and

(e) about 0.5 to about 1.5% by weight magnesium stearate.

17. The oral dosage form of claim 2, wherein the powder comprises:

(a) about 78.5 to about 79.5% by weight propafenone;

(b) about 4.5 to about 5.5% by weight povidone;

(c) about 2.5 to about 3.5% by weight glyceryl behenate;

(d) about 11.5 to about 12.5% by weight lactose anhydrous; and

(e) about 0.5 to about 1.5% by weight magnesium stearate.

18. An oral dosage form of a pharmaceutically active ingredient comprising:

(a) about 78.5 to about 79.5% by weight propafenone;

(b) about 4.5 to about 5.5% by weight povidone;

(c) about 4.5 to about 5.5% by weight ethyl cellulose;

(d) about 9.5 to about 10.5% by weight lactose anhydrous, and

(e) about 0.5 to about 1.5% by weight magnesium stearate.

19. An oral dosage form of a pharmaceutically active ingredient comprising:

(a) about 78.5 to about 79.5% by weight propafenone;

(b) about 4.5 to about 5.5% by weight povidone;

(c) about 2.5 to about 3.5% by weight glyceryl behenate;

(d) about 11.5 to about 12.5% by weight lactose anhydrous; and

(e) about 0.5 to about 1.5% by weight magnesium stearate.

20. A method of producing an oral dosage form of a pharmaceutically active ingredient comprising:

(a) compressing a powder comprising a pharmaceutically active ingredient into slugs,

(b) breaking the slugs into non-uniform pellets, having a non-uniform shape and/or size, and

(c) encapsulating the non-uniform pellets in a capsule.

21. The method of claim 20, wherein the compressing step comprises roller compaction.

22. The method of claim 20, further comprising, subsequent to step (a) and prior to step (b), scoring at least one surface of the slugs.

23. The method of claim 20, wherein the compressing step results in the formation of compressed slugs comprising scoring on at least one surface.

24. The method of claim 23, wherein the depth of the scoring comprises up to about 95% of the thickness of the slugs.

25. The method of claim 20, wherein the non-uniform pellets have a diameter of from about 1 mm to about 3 mm.

26. The method of claim 20, wherein the non-uniform pellets have a maximum and a minimum diameter, each of which is independently from about 1 mm to about 3 mm.

27. The method of claim 20, wherein the non-uniform pellets are primarily spherical, cubic, cylindrical, irregular, or a combination thereof.

28. The method of claim 20, further comprising, subsequent to step (b) and prior to step (c), coating the non-uniform pellets with a pharmaceutically acceptable coating material.

29. The method of claim 20, wherein the active ingredient is selected from the group consisting of doxycycline, omeprazole, esomeprazole, and propafenone.

30. The method of claim 20, wherein the powder comprises:

(a) about 78.5 to about 79.5% by weight propafenone;

(b) about 4.5 to about 5.5% by weight povidone;

(c) about 4.5 to about 5.5% by weight ethyl cellulose;

(d) about 9.5 to about 10.5% by weight lactose anhydrous, and

(e) about 0.5 to about 1.5% by weight magnesium stearate.

31. The method of claim 20, wherein the powder comprises:

(a) about 78.5 to about 79.5% by weight propafenone;

(b) about 4.5 to about 5.5% by weight povidone;

(c) about 2.5 to about 3.5% by weight glyceryl behenate;

(d) about 11.5 to about 12.5% by weight lactose anhydrous; and

(e) about 0.5 to about 1.5% by weight magnesium stearate.

32. The method of claim 20, further comprising, subsequent to step (b) and prior to step (c), screening the pellets for a desired shape and/or size profile.

33. An apparatus for making compressed powder slugs that are scored for breaking into pellets, comprising:

tooling that is adapted to compress powder into a slug, wherein at least one surface of the tooling is adapted to form scoring on at least one surface of the slug, for breaking the slug into pellets.

34. The apparatus of claim 33, wherein the tooling comprises a die, a lower punch, and an upper punch.

35. The apparatus of claim 34, wherein at least one of the upper punch and the lower punch is adapted to form scoring on a surface of the slug.

36. The apparatus of claim 35, wherein both the upper punch and the lower punch are adapted to form scoring on upper and lower surfaces of the slug.

37. The apparatus of claim 36, wherein the upper punch and the lower punch are adapted to form scoring of different depths on upper and lower surfaces of the slug, respectively.

38. The apparatus of claim 33, wherein the scoring is adapted for breaking the slug into at least two pellets.

39. The apparatus of claim 33, wherein the scoring is adapted for breaking the slug into at least twenty pellets.

40. The apparatus of claim 33, wherein the tooling is adapted to form a single slug.

41. The apparatus of claim 33, wherein the tooling is adapted to form multiple slugs.

42. A punch for making compressed powder slugs that are scored for breaking into pellets, comprising:

a device adapted to form scoring on a surface of the slug, for breaking the slug into pellets.

43. The punch of claim 42, wherein the device is adapted to form scoring with an angle of from about 15°

to about 90°

between a line that is tangential to the surface of the slug that comprises the scoring and a line perpendicular to an outer surface of the slug.