PROCESS FOR PREPARING OXYCODONE COMPOSITIONS
In certain embodiments the invention is directed to a process for preparing an oxycodone hydrochloride composition having less than 25 ppm of 14-hydroxycodeinone.
1 - 79 . (canceled)
80 . A process for preparing an oxycodone salt composition, which process comprises:
combining (i) an oxycodone free base composition comprising a first amount of 14-hydroxycodeinone and (ii) an acid under conditions to provide an oxycodone salt composition comprising a second amount of 14-hydroxycodeinone, the second amount of 14-hydroxycodeinone being lower than the first amount of 14-hydroxycodeinone.
81 . The process of claim 80 , wherein the oxycodone free base composition comprises 8α,14-dihydroxy-7,8-dihydrocodeinone.
82 . The process of claim 81 , wherein the conditions reduce the rate of dehydration of the 8α,14-dihydroxy-7,8-dihydrocodeinone to 14-hydroxycodeinone.
83 . The process of claim 82 , wherein at least some of the 8α,14-dihydroxy-7,8-dihydrocodeinone is dehydrated to the 14-hydroxycodeinone during the process.
84 . The process of claim 80 , wherein the conditions comprise a temperature of from about 20° C. to about 100° C.
85 . The process of claim 80 , wherein the conditions comprise a hydrogen pressure from about 40 PSIG to about 60 PSIG.
86 . The process of claim 80 , wherein the oxycodone free base composition and the acid are combined in a solvent.
87 . The process of claim 86 , wherein the solvent comprises an alcohol.
88 . The process of claim 80 , wherein the acid is hydrochloric acid.
89 . The process of claim 80 , wherein the process is for preparing an oxycodone hydrochloride salt composition.
90 . The process of claim 89 , wherein the oxycodone hydrochloride salt composition comprises less than 100 ppm of 14-hydroxycodeinone.
91 . The process of claim 90 , wherein the oxycodone hydrochloride salt composition comprises 1 ppm or more 14-hydroxycodeinone.
92 . A process for preparing an oxycodone composition, which process comprises steps of:
(a) preparing a mixture comprising a first oxycodone composition and an acid, the first oxycodone composition comprising a first amount of 14-hydroxycodeinone; and
(b) incubating the mixture to provide a second oxycodone composition comprising a second amount of 14-hydroxycodeinone, the second amount of 14-hydroxycodeinone being lower than the first amount of 14-hydroxycodeinone.
93 . The process of claim 92 , wherein the first oxycodone composition comprises 8α,14-dihydroxy-7,8-dihydrocodeinone.
94 . The process of claim 93 , wherein the mixture is incubated under conditions which promote an acid catalyzed dehydration consisting of conversion of the 8α,14-dihydroxy-7,8-dihydrocodeinone to 14-hydroxycodeinone.
95 . The process of claim 93 , wherein at least some of the 8α,14-dihydroxy-7,8-dihydrocodeinone is dehydrated to the 14-hydroxycodeinone during the process.
96 . The process of claim 92 , wherein the mixture further comprises a solvent.
97 . The process of claim 96 , wherein the solvent comprises an alcohol.
98 . The process of claim 92 , wherein step (b) is conducted at a temperature of from about 20° C. to about 100° C.
99 . The process of claim 92 , wherein the process is for preparing an oxycodone hydrochloride salt composition.
100 . The process of claim 99 , wherein the second oxycodone composition comprises less than 100 ppm of 14-hydroxycodeinone.
101 . The process of claim 100 , wherein the oxycodone salt composition comprises 1 ppm or more 14-hydroxycodeinone.
102 . The process of claim 92 , wherein the second oxycodone composition is an oxycodone salt composition.
103 . The process of claim 102 , wherein the oxycodone salt composition is an oxycodone hydrochloride salt composition.
104 . A process for preparing an oxycodone composition, which process comprises steps of:
(a) providing a solution comprising a first oxycodone composition comprising 8α,14-dihydroxy-7,8-dihydrocodeinone and a first amount of 14-hydroxycodeinone;
(b) controlling an acid catalyzed dehydration consisting of conversion of 8α,14-dihydroxy-7,8-dihydrocodeinone to 14-hydroxycodeinone in the solution to provide a second oxycodone composition comprising a second amount of 14-hydroxycodeinone, the second amount of 14-hydroxycodeinone being lower than the first amount of 14-hydroxycodeinone; and
(c) isolating the second oxycodone composition comprising the second amount of 14-hydroxycodeinone.
105 . The process of claim 104 , wherein at least some of the 8α,14-dihydroxy-7,8-dihydrocodeinone is dehydrated to 14-hydroxycodeinone during the process.
106 . The process of claim 103 , wherein the second oxycodone composition is substantially free of 14-hydroxycodeinone.
107 . The process of claim 106 , wherein the second oxycodone composition comprises less than 100 ppm 14-hydroxycodeinone.
108 . A process for preparing an oxycodone salt composition, which process comprises:
combining (i) an oxycodone free base composition comprising 8α,14-dihydroxy-7,8-dihydrocodeinone and an amount of 14-hydroxycodeinone and (ii) an acid under conditions to provide an oxycodone salt composition comprising a decreased amount of 14-hydroxycodeinone.
109 . The process of claim 108 , wherein the decreased amount of 14-hydroxycodeinone is less than 100 ppm.