Oxycodone hydrochloride having less than 25 PPM 14-hydroxycodeinone

• US 20070179169A1
• Filed: 03/29/2007
• Published: 08/02/2007
• Est. Priority Date: 03/30/2004
• Status: Active Grant

• Current Assignee: Purdue Pharma L.P.
• Original Assignee: Euroceltique SA
• Inventors: Hong, Qi, Kyle, Donald, Chapman, Robert, Kupper, Robert, Rider, Lonn
• Granted Patent: US 7,674,800 B2
• Time in Patent Office: Days
• US Class Current: 514/282
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 9/14 Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles microspheres A61K9/16; microcapsules A61K9/50; nanocapsules, nanoparticles of the matrix type A61K9/51
• CPC Class Codes: A61K 9/20 Pills, tablets, discs, rods A61K9/0004, A61K9/0007, A61K9/0056, A61K9/0065 take precedence; for reconstitution of a drink A61K9/0095
• CPC Class Codes: A61K 9/2095 Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing mechanical aspects A61J3/00
• CPC Class Codes: A61K 9/48 Preparations in capsules, e.g. of gelatin, of chocolate A61K9/0004 takes precedence; bite capsules A61K9/0056
• CPC Class Codes: A61K 9/4833 Encapsulating processes; Filling of capsules mechanical aspects A61J3/07
• 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]
• CPC Class Codes: C07D 489/02 with oxygen atoms attached in positions 3 and 6, e.g. morphine, morphinone
• CPC Class Codes: C07D 489/04 Salts; Organic complexes
• CPC Class Codes: C07D 489/08 Oxygen atom

Abstract

In certain embodiments the invention is directed to a process for preparing an oxycodone hydrochloride composition having less than 25 ppm of 14-hydroxycodeinone.

Claims

1-70. -70. (canceled)

71. An oxycodone hydrochloride composition having less than 25 ppm 14-hydroxycodeinone,

the oxycodone hydrochloride composition prepared by a process comprising:

hydrogenating an oxycodone hydrochloride composition having at least 100 ppm 14-hydroxycodeinone in a suitable solvent to produce the oxycodone hydrochloride composition having less than 25 ppm 14-hydroxycodeinone.

72. The oxycodone hydrochloride composition of claim 71, wherein the hydrogenation is performed with a hydrogen donor and a catalyst.

73. The oxycodone hydrochloride composition of claim 71, wherein the hydrogenation is performed under reflux.

74. The oxycodone hydrochloride composition of claim 71, wherein the solvent is an alcohol.

75. The oxycodone hydrochloride composition of claim 74, wherein the alcohol is selected from the group consisting of methanol, ethanol and isopropanol.

76. The oxycodone hydrochloride composition of claim 71, wherein the process further comprises recovering the oxycodone hydrochloride composition having less than 25 ppm 14-hydroxycodeinone from the solvent.

77. The oxycodone hydrochloride composition of claim 76, wherein the recovery step of the process comprises crystallizing the oxycodone hydrochloride composition having less than 25 ppm 14-hydroxycodeinone and filtering the crystallized composition from the solvent.

78. The oxycodone hydrochloride composition of claim 76, wherein the process comprises further hydrogenating the oxycodone hydrochloride composition having less than 25 ppm 14-hydroxycodeinone.

79. The oxycodone hydrochloride composition of claim 76, wherein the oxycodone hydrochloride composition has a 14-hydroxycodeinone level of less than 15 ppm.

80. The oxycodone hydrochloride composition of claim 72, wherein the hydrogenation is performed with a hydrogen donor.

81. The oxycodone hydrochloride composition of claim 80, wherein the hydrogenation is further performed with a catalyst.

82. The oxycodone hydrochloride composition of claim 80, wherein the hydrogen donor is selected from the group consisting of hydrogen gas, formic acid, indoline, cyclohexene, sodium borohydride, tetrahydroquinoline, 2,5-dihydrofuran, phosphoric acid, and combinations thereof.

83. The oxycodone hydrochloride composition of claim 71, having a 14-hydroxycodeinone level of less than 15 ppm, wherein the hydrogenation produces an oxycodone hydrochloride composition having a 14-hydroxycodeinone level of less than 15 ppm.

84. The oxycodone hydrochloride composition of claim 71, having a 14-hydroxycodeinone level of less than 10 ppm, wherein the hydrogenation produces an oxycodone hydrochloride composition having a 14-hydroxycodeinone level of less than 10 ppm.

85. The oxycodone hydrochloride composition of claim 71, having a 14-hydroxycodeinone level of less than 5 ppm, wherein the hydrogenation produces an oxycodone hydrochloride composition having a 14-hydroxycodeinone level of less than 5 ppm.

86. The oxycodone hydrochloride composition of claim 71, having a 14-hydroxycodeinone level of less than 10 ppm, wherein the hydrogenation produces an oxycodone composition having a 14-hydroxycodeinone level of between 15 ppm and 25 ppm, and the process further comprises additional hydrogenation to produce an oxycodone hydrochloride composition comprising 14-hydroxycodeinone in an amount less than 10 ppm.

87. The oxycodone hydrochloride composition of claim 71, having a 14-hydroxycodeinone level of less than 5 ppm, wherein the hydrogenation produces an oxycodone composition having a 14-hydroxycodeinone level of between 10 ppm and 25 ppm, and the process further comprises additional hydrogenation to produce an oxycodone hydrochloride composition comprising 14-hydroxycodeinone in an amount less than 5 ppm.

88. The oxycodone hydrochloride composition of claim 71, wherein the hydrogenation step is performed without a hydrogen gas feed.