ONCE-A-DAY OXYCODONE FORMULATIONS

• US 20110104214A1
• Filed: 11/01/2010
• Published: 05/05/2011
• Est. Priority Date: 04/15/2004
• Status: Abandoned Application

• Current Assignee: Purdue Pharma L.P.
• Original Assignee: Purdue Pharma L.P.
• Inventors: Prater, Derek, Wright, Curtis, Oshlack, Benjamin
• Application Number:
  US12/917,148
• Publication Number:
  US 20110104214A1
• Time in Patent Office: Days
• US Class Current: 424/400
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 9/0004 Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas
• CPC Class Codes: A61K 9/1617 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/1635 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/2018 Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
• CPC Class Codes: A61K 9/2027 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/2031 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/2086 Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat active cores with a complete drug-free outer coat A61K9/28
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids

Abstract

The invention is directed to sustained release formulations containing oxycodone or a pharmaceutically acceptable salt thereof which provide a mean C₂₄/C_max oxycodone ratio of 0.6 to 1.0 or 0.7 to 1 after oral administration at steady state to patients and methods thereof.

Claims

1-22. -22. (canceled)

23. A sustained release oral dosage form comprising:

(a) a bilayer core comprising;

(i) a drug layer comprising an analgesically effective amount of oxycodone or a pharmaceutically acceptable salt thereof; and

(ii) a displacement layer comprising an osmopolymer; and

(b) a semipermeable wall surrounding the bilayer core having a passageway disposed therein for the release of said oxycodone or pharmaceutically acceptable salt thereof;

said dosage form providing an analgesic effect for at least about 24 hours after steady-state oral administration to human patients; and

said dosage form providing a mean C₂₄/C_max oxycodone ratio of 0.6 to 1.0 after oral administration at steady state to said patients.

24. The dosage form of claim 23, which provides a mean T_max of oxycodone in about 2 to about 17 hours after administration at steady state to said patients.

25. The dosage form of claim 23, which provides a mean T_max of oxycodone in about 8 to about 16 hours after administration at steady state to said patients.

26. The dosage form of claim 23, which provides a mean W₅₀ of the oxycodone of between 4 and 24 hours after administration at steady state to said patients.

27. The dosage form of claim 23, which provides a W₅₀ of the oxycodone of at least 12 hours after administration at steady state to said patients.

28. The dosage form of claim 23, wherein said displacement layer further comprises an osmagent.

29. The dosage form of claim 28, wherein said osmagent is selected from the group consisting of osmotic salts and osmotic carbohydrates.

30. The dosage form of claim 23, wherein said pharmaceutically acceptable salt of oxycodone is oxycodone hydrochloride.

31. The dosage form of claim 23, wherein said oxycodone or pharmaceutically acceptable salt thereof is in an amount of from about 5 to about 640 mg.

32. The dosage form of claim 23, which provides a mean T_max of oxycodone which occurs at about 12 to about 16 hours after administration at steady state to said patients.

33. The dosage form of claim 23, which provides a mean C₂₄/C_max ratio of 0.7 to 0.99 after administration at steady state to said patients.

34. The dosage form of claim 23, which provides a mean C₂₄/C_max ratio of 0.8 to 0.95 after administration at steady state to said patients.

35. The dosage form of claim 23, which provides an in-vitro release rate, of oxycodone or a pharmaceutically acceptable salt thereof, when measured by the USP Basket Method at 100 rpm in 900 ml aqueous buffer at a pH of between 1.6 and 7.2 at 37°

C. of from 0% to about 40% at 1 hour, from about 8% to about 70% at 4 hours, from about 20% to about 80% at 8 hours, from about 30% to about 95% at 12 hours, from about 35% to about 95% at 18 hrs, and greater than about 50% at 24 hours.

72. The dosage form of claim 23, which is overcoated with an additional amount of oxycodone or a pharmaceutically acceptable salt thereof in an immediate release form.

36. A method of treating pain in patients comprising:

orally administering to human patients a sustained release oral dosage form comprising

(a) a bilayer core comprising;

(i) a drug layer comprising an analgesically effective amount of oxycodone or a pharmaceutically acceptable salt thereof; and

(ii) a displacement layer comprising an osmopolymer; and

(b) a semipermeable wall surrounding the bilayer core having a passageway disposed therein for the release of said oxycodone or pharmaceutically acceptable salt thereof;

to provide an analgesic effect at least about 24 hours after oral administration at steady state to human patients; and

to provide a mean C₂₄/C_max oxycodone ratio of 0.6 to 1.0 after oral administration at steady state to said patients.

37. The method of claim 36, which provides a mean T_max of oxycodone at about 2 to about 17 hours after administration at steady state to said patients.

38. The method of claim 36, which provides a mean T_max of oxycodone at about 8 to about 16 hours after administration at steady state to said patients.

39. The method of claim 36, which provides a W₅₀ of the oxycodone of between 4 and 24 hours after administration at steady state to said patients.

40. The method of claim 39, which provides a W₅₀ of the oxycodone of at least 12 hours after administration at steady state to said patients.

41. The method of claim 36, which provides a mean C₂₄/C_max ratio of 0.7 to 0.99 after administration at steady state to said patients.

42. The method of claim 36, which provides a mean C₂₄/C_max ratio of 0.8 to 0.95 after administration at steady state to said patients.

43. The method of claim 36, wherein said dosage form provides an in-vitro release rate of oxycodone or a pharmaceutically acceptable salt thereof, when measured by the USP Basket Method at 100 rpm in 900 ml aqueous buffer at a pH of between 1.6 and 7.2 at 37°

C. of from 0% to about 40% at 1 hour, from about 8% to about 70% at 4 hours, from about 20% to about 80% at 8 hours, from about 30% to about 95% at 12 hours, from about 35% to about 95% at 18 hrs, and greater than about 50% at 24 hours.

44-71. -71. (canceled)

73. An osmotic dosage form comprising

a homogeneous core comprising oxycodone or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable polymer;

and

a semipermeable membrane having a passageway, the semipermeable membrane surrounding the homogeneous core;

wherein the dosage form provides an analgesic effect for at least about 24 hours and a mean C₂₄/C_max oxycodone ratio of 0.7 to 1 after steady-state oral administration to human patients.

74. The dosage form of claim 73, which is overcoated with additional oxycodone and pharmaceutically acceptable salt thereof in an immediate release form.

75. The dosage form of claim 73, wherein the pharmaceutically acceptable polymer is polyethylene oxide.

76. The dosage form of claim 73, further comprising a disintegrant.

77. The dosage form of claim 73, further comprising an absorption enhancer.

78. The dosage form of claim 73, wherein the semipermeable membrane comprises a poly(cellulose) with a number-average molecular weight of 20,000 to 7,500,000.

79. The dosage form of claim 78, wherein the poly(cellulose) is selected from the group consisting of a cellulose ester polymer, a cellulose ether polymer and cellulose ester-ether polymer.

80. An osmotic dosage form comprising:

1 to 640 mg of oxycodone or a pharmaceutically acceptable salt thereof,

25 to 500 mg of poly(alkylene oxide having a 150,000 to 500,000 average molecular weight,

1 to 50 mg of polyvinylpyrrolidone) having a 40,000 average molecular weight, and

0 to about 7.5 mg of a lubricant,

wherein the dosage form provides an analgesic effect for at least about 24 hours and a mean C₂₄/C_max oxycodone ratio of 0.7 to 1 after steady-state oral administration to human patients.