GASTRIC RETENTIVE EXTENDED-RELEASE DOSAGE FORMS COMPRISING COMBINATIONS OF A NON-OPIOID ANALGESIC AND AN OPIOID ANALGESIC

• US 20120321713A1
• Filed: 06/21/2012
• Published: 12/20/2012
• Est. Priority Date: 03/11/2008
• Status: Active Grant

• Current Assignee: Assertio Therapeutics, Inc. (Assertio Holdings, Inc.)
• Original Assignee: Depomed Incorporated (Assertio Holdings, Inc.)
• Inventors: Hou, Sui Yuen Eddie, Reid, Monica L., HAN, CHIEN-HSUAN
• Granted Patent: US 8,668,929 B2
• Time in Patent Office: Days
• US Class Current: 424/486
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/167 having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
• CPC Class Codes: A61K 31/4355 the heterocyclic ring system containing a five-membered ring having oxygen as a ring hetero atom
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/12 Carboxylic acids; Salts or anhydrides thereof
• CPC Class Codes: A61K 47/32 Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers , poly(meth)acrylates, or polyvinyl pyrrolidone
• CPC Class Codes: A61K 47/38 Cellulose; Derivatives thereof
• CPC Class Codes: A61K 9/0065 Forms with gastric retention, e.g. floating on gastric juice, adhering to gastric mucosa, expanding to prevent passage through the pylorus
• CPC Class Codes: A61K 9/0087 Galenical forms not covered by A61K9/02 - A61K9/7023
• CPC Class Codes: A61K 9/209 containing drug in at least two layers or in the core and in at least one outer layer
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Abstract

Compositions and methods for the treatment of pain in a mammal are described. More specifically, a dosage form designed for release of acetaminophen and an opioid is described, wherein the dosage form provides delivery of the drugs to the upper gastrointestinal tract (“GI”) of a mammal for an extended period of time.

Claims

1. A method for treating pain, comprising:

administering at least twice daily, a dosage form comprising a dose of acetaminophen and a dose of an opioid, wherein the dosage form comprises an extended release matrix that imbibes fluid after administration and swells to a size sufficient to promote gastric retention of the matrix, wherein within about 1 hour in an in vitro disintegration test the dosage form releases more than about 50% of the dose of acetaminophen, and wherein by about 6 hours in an in vitro disintegration test, the percent of opioid released from the dosage form is greater than the percent of acetaminophen released from the dosage form, and wherein the in vitro disintegration test is a USP type II apparatus at 37°

C. in 0.1 N HCl.

2. The method of claim 1, wherein substantially all of the doses of acetaminophen and the opioid are released within about ten hours in an in vitro disintegration test.

3. The method of claim 1, wherein the dose of acetaminophen in the dosage form is between about 100-1300 mg.

4. The method of claim 1, wherein the dose of opioid in the dosage form is between about 5-40 mg.

5. The method of claim 4, wherein the dosage form comprises an opioid selected from the group consisting of oxycodone, hydrocodone, and pharmaceutically acceptable salts thereof.

6. The method of claim 3, wherein the dose of opioid in the dosage form is between about 5-40 mg.

7. The method of claim 6, wherein the dosage form comprises an opioid selected from the group consisting of oxycodone, hydrocodone, and pharmaceutically acceptable salts thereof.

8. The method of claim 1, wherein the dosage form comprises an immediate release portion.

9. The method of claim 7, wherein the dosage form comprises an immediate release portion.

10. The method of claim 9, wherein the dosage form comprises between about 20-50 weight percent of poly(ethylene oxide).

11. The method of claim 10, wherein the poly(ethylene oxide) has a molecular weight of between about 900,000 Daltons to about 4,000,000 Daltons.

12. The method of claim 1, wherein the dosage form comprises between about 20-50 weight percent of poly(ethylene oxide).

13. The method of claim 12, wherein the poly(ethylene oxide) has a molecular weight of between about 900,000 Daltons to about 2,000,000 Daltons.

14. A method for treating pain, comprising:

administering at least twice daily, a dosage form comprising a dose of acetaminophen and a dose of an opioid, wherein the dosage form comprises an extended release matrix that imbibes fluid after administration and swells to a size sufficient to promote gastric retention of the matrix, wherein at about 1 hour in an in vitro disintegration test the percent of acetaminophen released by the dosage form is greater than the percent of opioid released, and wherein by about 4-6 hours in an in vitro disintegration test, the dosage form releases greater than 90% of the dose of acetaminophen and the cumulative percent of opioid released is within about 10% of the cumulative percent of acetaminophen released, and wherein the in vitro disintegration test is a USP type II apparatus at 37°

C. in 0.1 N HCl.

15. The method of claim 14, wherein substantially all of the doses of acetaminophen and the opioid are released within about ten hours in an in vitro disintegration test.

16. The method of claim 14, wherein the dose of acetaminophen in the dosage form is between about 100-1300 mg.

17. The method of claim 14, wherein the dose of opioid in the dosage form is between about 5-40 mg.

18. The method of claim 17, wherein the dosage form comprises an opioid selected from the group consisting of oxycodone, hydrocodone, and pharmaceutically acceptable salts thereof.

19. The method of claim 16, wherein the dose of opioid in the dosage form is between about 5-40 mg.

20. The method of claim 19, wherein the dosage form comprises an opioid selected from the group consisting of oxycodone, hydrocodone, and pharmaceutically acceptable salts thereof.

21. The method of claim 14, wherein the dosage form comprises an immediate release portion.

22. The method of claim 20, wherein the dosage form comprises an immediate release portion.

23. The method of claim 22, wherein the dosage form comprises between about 20-50 weight percent of poly(ethylene oxide).

24. The method of claim 23, wherein the poly(ethylene oxide) has a molecular weight of between about 900,000 Daltons to about 4,000,000 Daltons.

25. The method of claim 14, wherein the dosage form comprises between about 20-50 weight percent of poly(ethylene oxide).

26. The method of claim 25, wherein the poly(ethylene oxide) has a molecular weight of between about 900,000 Daltons to about 2,000,000 Daltons.

27. A method for treating pain, comprising:

administering at least twice daily, a dosage form comprising a dose of acetaminophen and a dose of an opioid, wherein the dosage form comprises an extended release matrix that imbibes fluid after administration and swells to a size sufficient to promote gastric retention of the matrix, wherein in an in vitro disintegration test the percent of acetaminophen released is greater than the percent of opioid released at times of 3 hours or less, at times greater than about 6 hours, the percent of opioid released is greater than the percent of acetaminophen released, and wherein the in vitro disintegration test is a USP type II apparatus at 37°

C. in 0.1N HCl.

28. The method of claim 27, wherein substantially all of the doses of acetaminophen and the opioid are released within about ten hours in an in vitro disintegration test.

29. The method of claim 27, wherein the dose of acetaminophen in the dosage form is between about 100-1300 mg.

30. The method of claim 27, wherein the dose of opioid in the dosage form is between about 5-40 mg.

31. The method of claim 30, wherein the dosage form comprises an opioid selected from the group consisting of oxycodone, hydrocodone, and pharmaceutically acceptable salts thereof.

32. The method of claim 29, wherein the dose of opioid in the dosage form is between about 5-40 mg.

33. The method of claim 32, wherein the dosage form comprises an opioid selected from the group consisting of oxycodone, hydrocodone, and pharmaceutically acceptable salts thereof.

34. The method of claim 27, wherein the dosage form comprises an immediate release portion.

35. The method of claim 33, wherein the dosage form comprises an immediate release portion.

36. The method of claim 35, wherein the dosage form comprises between about 20-50 weight percent of poly(ethylene oxide).

37. The method of claim 36, wherein the poly(ethylene oxide) has a molecular weight of between about 900,000 Daltons to about 4,000,000 Daltons.

38. The method of claim 27, wherein the dosage form comprises between about 20-50 weight percent of poly(ethylene oxide).

39. The method of claim 38, wherein the poly(ethylene oxide) has a molecular weight of between about 900,000 Daltons to about 2,000,000 Daltons.