CONTROLLED RELEASE HYDROCODONE FORMULATIONS

• US 20160151292A1
• Filed: 02/09/2016
• Published: 06/02/2016
• Est. Priority Date: 10/30/2000
• Status: Active Grant

• Current Assignee: Purdue Pharma L.P.
• Original Assignee: Purdue Pharma L.P.
• Inventors: Oshlack, Benjamin, Huang, Hua-pin, Masselink, John K., Tonelli, Alfred
• Granted Patent: US 9,572,804 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 31/194 having two or more carboxyl groups, e.g. succinic, maleic or phthalic acid
• CPC Class Codes: A61K 31/46 8-Azabicyclo [3.2.1] octane; Derivatives thereof, e.g. atropine, cocaine
• 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 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61K 9/141 Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers (co) spray-dried products A61K9/16, (co) lyophilised products A61K9/19; the carrier being chemically bound to the active ingredient A61K47/50
• CPC Class Codes: A61K 9/2009 Inorganic compounds
• CPC Class Codes: A61K 9/2013 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/2018 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 9/205 Polysaccharides, e.g. alginate, gums; Cyclodextrin
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/2072 characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms A61K9/0004, A61K9/0056, A61K9/0065 take precedence
• CPC Class Codes: A61K 9/2077 Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
• 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
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Abstract

A solid oral controlled-release dosage form of hydrocodone is disclosed, the dosage form comprising an analgesically effective amount of hydrocodone or a pharmaceutically acceptable salt thereof, and controlled release material.

Claims

1-38. -38. (canceled)

39. A solid oral controlled-release dosage form of hydrocodone, the dosage form comprising a matrix comprising hydrocodone or a pharmaceutically acceptable salt thereof and a cellulose ether, such that the dosage form provides a ratio of a plasma concentration of hydrocodone at the end of a dosing interval to a maximum plasma concentration of hydrocodone during the dosing interval of from 0.55 to 1 and effective pain relief over a period of time of about 12 hours or longer after administration to a human patient, wherein

the dosage form is a tablet, and

the hydrocodone or pharmaceutically acceptable salt thereof is the only active agent in the dosage form.

40. The dosage form of claim 39, wherein the effective pain relief is provided for about 12 hours.

41. The dosage form of claim 40, wherein said administration is first administration.

42. The dosage form of claim 41, wherein the cellulose ether comprises a hydroxyalkylcellulose.

53. The dosage form of claim 39, wherein the dosage form provides a mean C₂₄/C_max hydrocodone ratio of from 0.55 to 1 after administration to a patient population and the dosing interval is 24 hours.

54. The dosage form of claim 39, wherein the dosage form provides a C₂₄/C_max hydrocodone ratio of from 0.55 to 1 after administration to the human patient and the dosing interval is 24 hours.

60. The dosage form of claim 39, wherein the cellulose ether comprises ethylcellulose.

65. The dosage form of claim 39, wherein the matrix comprises a wax.

66. The dosage form of claim 39, wherein the dosage form provides a mean ratio of mean plasma concentrations of hydrocodone at the end of a dosing interval to mean maximum plasma concentrations of hydrocodone during the dosing interval of from 0.55 to 1 after administration to a patient population.

67. The dosage form of claim 66, which provides a C₂₄/C_max hydrocodone ratio of from 0.55 to 1 after said administration and the dosing in.

43. A solid oral controlled-release dosage form of hydrocodone, the dosage form comprising a matrix comprising hydrocodone or a pharmaceutically acceptable salt thereof and a cellulose ether, such that the dosage form provides a W₅₀ of hydrocodone of between 4 and 22 hours and a plasma concentration of hydrocodone within a therapeutic range over a period of time of about 12 hours or longer after administration to a human patient, wherein

the dosage form is a tablet, and

the hydrocodone or pharmaceutically acceptable salt thereof is the only active agent in the dosage form.

44. The dosage form of claim 43, wherein the dosage form provides the plasma concentration of hydrocodone within the therapeutic range over a period of time of about 12 hours after administration to the human patient.

45. The dosage form of claim 44, wherein said administration is first administration.

46. The dosage form of claim 43, wherein said administration is first administration.

47. The dosage form of claim 43, wherein the cellulose ether comprises a hydroxyalkylcellulose.

48. The dosage form of claim 43, wherein the dosage form provides a C₂₄/C_max hydrocodone ratio of from 0.55 to 1.

49. A solid oral controlled-release dosage form of hydrocodone, the dosage form comprising a matrix comprising hydrocodone or a pharmaceutically acceptable salt thereof and a cellulose ether, such that the dosage form provides a T_max of hydrocodone of from about 4 to about 14 hours and a plasma concentration of hydrocodone within a therapeutic range over a period of time of about 12 hours or longer after administration to a human patient, wherein

the dosage form is a tablet, and

the hydrocodone or a pharmaceutically acceptable salt thereof is the only active agent in the dosage form.

50. The dosage form of claim 49, wherein the dosage form provides the plasma concentration of hydrocodone within the therapeutic range over a period of time of about 12 hours after administration to the human patient.

51. The dosage form of claim 50, wherein said administration is first administration.

52. The dosage form of claim 49, wherein said administration is first administration.

55. The dosage form of claim 49, wherein the cellulose ether comprises a hydroxyalkylcellulose.

56. A solid oral controlled-release dosage form of hydrocodone, the dosage form comprising a matrix comprising hydrocodone bitartrate and a cellulose ether, such that the dosage form provides a plasma concentration of hydrocodone within a therapeutic range over a period of time of about 12 hours or longer after administration to a human patient, wherein

the dosage form is a tablet, and

the hydrocodone bitartrate is the only active agent in the dosage form.

57. The dosage form of claim 56, wherein the cellulose ether comprises a hydroxyalkylcellulose.

58. The dosage form of claim 56, wherein the cellulose ether comprises ethylcellulose.

59. The dosage form of claim 56, wherein the dosage form provides a mean C₂₄/C_max hydrocodone ratio of from 0.55 to 1 after administration to a patient population.

61. The dosage form of claim 56, wherein the dosage form provides an in-vitro release of hydrocodone when measured by the USP Basket method at 100 rpm in 700 ml aqueous buffer at a pH of 1.2 at 37°

C. of from 10% to about 45% by weight hydrocodone released at 1 hour.

62. The dosage form of claim 56, wherein the dosage form provides the plasma concentration of hydrocodone within the therapeutic range over a period of time of about 12 hours after administration to the human patient.

63. The dosage form of claim 62, wherein said administration is first administration.

64. The dosage form of claim 56, wherein said administration is first administration.

68. The dosage form of claim 56, wherein the matrix comprises a wax.