IMMEDIATE RELEASE PHARMACEUTICAL COMPOSITIONS COMPRISING OXYCODONE AND NALOXONE

• US 20120088786A1
• Filed: 03/10/2010
• Published: 04/12/2012
• Est. Priority Date: 03/10/2009
• Status: Active Grant

• Current Assignee: Purdue Pharma L.P.
• Original Assignee: Purdue Pharma L.P.
• Inventors: Hayes, Geoffrey Gerard, Mohammad, Hassan, Walden, Malcolm, Dadagher, Helen Kathleen, Heun, Gerhard Josef, Whitehouse, Jonathon Oliver
• Granted Patent: US 9,271,940 B2
• Time in Patent Office: Days
• US Class Current: 514/282
• 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 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61K 9/2018 Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
• CPC Class Codes: A61K 9/2059 Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 29/02 without antiinflammatory effect
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

The present invention pertains to oral immediate release pharmaceutical compositions suitable for treating patients suffering from pain comprising oxycodone and naloxone or their pharmaceutically acceptable salts.

Claims

1. An oral immediate release pharmaceutical composition comprising at least oxycodone or a pharmaceutically acceptable salt thereof and naloxone or a pharmaceutically acceptable salt thereof in about a 2:

1 ratio (oxycodone or a pharmaceutically acceptable salt thereof;

naloxone or a pharmaceutically acceptable salt thereof) by weight.

2. An oral immediate release pharmaceutical composition of claim 1, wherein the pharmaceutically acceptable salt of oxycodone and wherein the pharmaceutically acceptable salt of naloxone are selected from the hydrochloride salts of oxycodone and naloxone.

3. An oral immediate release pharmaceutical composition of claim 2, wherein the composition comprises oxycodone hydrochloride and naloxone hydrochloride as the sole pharmaceutically active agents.

4. An oral immediate release pharmaceutical composition of claim 1, wherein the formulation comprises an amount of oxycodone or a pharmaceutically acceptable salt thereof equivalent to about 1 mg to about 160 mg of oxycodone hydrochloride and an amount of naloxone or a pharmaceutically acceptable salt thereof equivalent to about 0.5 mg to about 80 mg of naloxone hydrochloride.

5. An oral immediate release pharmaceutical composition of claim 4, wherein the formulation comprises an amount of oxycodone or a pharmaceutically acceptable salt thereof equivalent to about 2.5 mg to about 40 mg of oxycodone hydrochloride and an amount of naloxone or a pharmaceutically acceptable salt thereof equivalent to about 1.25 mg to about 20 mg of naloxone hydrochloride.

6. An oral immediate release pharmaceutical composition of claim 5, wherein the formulation comprises an amount of oxycodone or a pharmaceutically acceptable salt thereof equivalent to about 2.5 mg to about 20 mg of oxycodone hydrochloride and an amount of naloxone or a pharmaceutically acceptable salt thereof equivalent to about 1.25 mg to about 10 mg of naloxone hydrochloride.

7. An oral immediate release pharmaceutical composition of claim 6, wherein the formulation comprises about 2.5 mg to about 20 mg of oxycodone hydrochloride and about 1.25 mg to about 10 mg of naloxone hydrochloride.

8. An oral immediate release pharmaceutical composition of claim 7, wherein the composition comprises oxycodone hydrochloride and naloxone hydrochloride as the sole pharmaceutically active agents.

9. An oral immediate release pharmaceutical composition of any of claim 1, wherein the formulation releases in vitro, when measured using the Ph. Eur. Paddle Method at 100 rpm in 0.1 N hydrochloric acid at 37°

C. and using UV detection at 230 nm, ≧

75% of oxycodone or a pharmaceutically acceptable salt thereof by weight and ≧

75% of naloxone or a pharmaceutically acceptable salt thereof by weight at 45 min.

10. An oral immediate release pharmaceutical composition of claim 9, wherein the formulation releases in vitro, when measured using the Ph. Eur. Paddle Method at 100 rpm in 0.1 N hydrochloric acid at 37°

C. and using UV detection at 230 nm, ≧

80% of oxycodone or a pharmaceutically acceptable salt thereof by weight and ≧

80% of naloxone or a pharmaceutically acceptable salt thereof by weight at 45 min.

11. An oral immediate release pharmaceutical composition of claim 9 or 10, wherein the formulation releases in vitro, when measured using the Ph. Eur. Paddle Method at 100 rpm in 0.1 N hydrochloric acid at 37°

C. and using UV detection at 230 nm, ≧

80% of oxycodone or a pharmaceutically acceptable salt thereof by weight and ≧

80% of naloxone or a pharmaceutically acceptable salt thereof by weight at 15 min.

12. An oral immediate release pharmaceutical composition of claim 11, wherein the formulation releases in vitro, when measured using the Ph. Eur. Paddle Method at 100 rpm in 0.1 N hydrochloric acid at 37°

C. and using UV detection at 230 nm, ≧

90% of oxycodone or a pharmaceutically acceptable salt thereof by weight and ≧

90% of naloxone or a pharmaceutically acceptable salt thereof by weight at 15 min.

13. An oral immediate release pharmaceutical composition of claim 12, wherein the formulation releases in vitro, when measured using the Ph. Eur. Paddle Method at 100 rpm in 0.1 N hydrochloric acid at 37°

C. and using UV detection at 230 nm, ≧

95% of oxycodone or a pharmaceutically acceptable salt thereof by weight and ≧

95% of naloxone or a pharmaceutically acceptable salt thereof by weight at 15 min.

14. An oral immediate release pharmaceutical composition of claim 1, wherein the composition is in the form of a tablet, of a capsule, of multiparticulates, of pellets, or of a liquid.

15. An oral immediate release pharmaceutical composition of claim 1, wherein the formulation comprises at least a diluents and optionally a disintegrant as pharmaceutically acceptable excipients.

16. An oral immediate release pharmaceutical composition of claim 1, wherein the formulation comprises at least a disintegrant and optionally a diluents as pharmaceutically acceptable excipients.

17. An oral immediate release pharmaceutical composition of claim 1, wherein the formulation comprises about 2.5 mg to about 20 mg of oxycodone hydrochloride and about 1.25 mg to about 10 mg of naloxone hydrochloride in about a 2:

1 ratio (oxycodone hydrochloride;

naloxone hydrochloride) by weight, wherein the composition comprises oxycodone hydrochloride and naloxone hydrochloride as the sole pharmaceutically active agents, wherein the composition is in solid form, optionally in the from of a tablet, wherein the formulation comprises at least a disintegrant and optionally a diluent as pharmaceutically acceptable excipients and wherein the formulation releases in vitro, when measured using the Ph. Eur. Paddle Method at 100 rpm in 0.1 N hydrochloric acid at 37°

C. and using UV detection at 230 nm, ≧

80% of oxycodone hydrochloride by weight and ≧

80% of naloxone hydrochloride by weight at 45 min.

18. An oral immediate release pharmaceutical composition of claim 17, wherein the formulation releases in vitro, when measured using the Ph. Eur. Paddle Method at 100 rpm in 0.1 N hydrochloric acid at 37°

C. and using UV detection at 230 nm, ≧

95% of oxycodone hydrochloride by weight and ≧

95% of naloxone hydrochloride by weight at 15 min.

30. Method of titrating a patient suffering from pain by administering an oral immediate release pharmaceutical composition of claim 1 or claim 19.

31. Method of treating breakthrough pain in a patient suffering from pain by administering an oral immediate release pharmaceutical composition of claim 1 or claim 19.

19. An oral immediate release pharmaceutical composition comprising oxycodone or a pharmaceutically acceptable salt thereof and naloxone or a pharmaceutically acceptable salt thereof, wherein the formulation releases in vitro, when measured using the Ph. Eur. Paddle Method at 100 rpm in 0.1 N hydrochloric acid at 37°

C. and using UV detection at 230 nm, ≧

90% of oxycodone or a pharmaceutically acceptable salt thereof by weight and ≧

90% of naloxone or a pharmaceutically acceptable salt thereof by weight at 15 min.

20. An oral immediate release pharmaceutical composition according to claim 19, wherein the formulation releases in vitro, when measured using the Ph. Eur. Paddle Method at 100 rpm in 0.1 N hydrochloric acid at 37°

C. and using UV detection at 230 nm, ≧

95% of oxycodone or a pharmaceutically acceptable salt thereof by weight and ≧

95% of naloxone or a pharmaceutically acceptable salt thereof by weight at 15 min.

21. An oral immediate release pharmaceutical composition according to claim 19, wherein the pharmaceutical composition comprises an amounts of oxycodone or a pharmaceutically acceptable salt thereof equivalent to about 1 mg to 160 mg of oxycodone hydrochloride and an amount of naloxone or a pharmaceutically acceptable salt thereof equivalent to about 0.5 mg to about 80 mg of naloxone hydrochloride.

22. An oral immediate release pharmaceutical composition according to claim 19, wherein the pharmaceutical composition comprises oxycodone or a pharmaceutically acceptable salt thereof and naloxone or a pharmaceutically acceptable salt thereof in about a 2:

1 ratio (oxycodone or a pharmaceutically acceptable salt thereof, naloxone or a pharmaceutically acceptable salt thereof) by weight.

23. An oral immediate release pharmaceutical composition according to claim 19, wherein the pharmaceutical composition is in solid form.

24. An oral immediate release pharmaceutical composition according to claim 19, wherein the pharmaceutical composition additionally comprises at least a disintegrant.

25. An oral immediate release pharmaceutical composition according to claim 19, wherein the pharmaceutical composition comprises oxycodone hydrochloride and naloxone hydrochloride as the sole pharmaceutically active agents.

26-29. -29. (canceled)