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 steps of:
(a) hydrogenating a 14-hydroxycodeinone composition to obtain an oxycodone free base composition comprising 8α,14-dihydroxy-7,8-dihydrocodeinone;
(b) converting the oxycodone free base composition comprising 8α,14-dihydroxy-7,8-dihydrocodeinone to a first oxycodone salt composition comprising a first amount of 14-hydroxycodeinone; and
(c) hydrogenating the first oxycodone salt composition comprising the first amount of 14-hydroxycodeinone to a second oxycodone salt composition comprising a second amount of 14-hydroxycodeinone;
wherein the second amount of 14-hydroxycodeinone is lower than the first amount of 14-hydroxycodeinone.
81 . The process of claim 80 , wherein the process is for preparing an oxycodone hydrochloride salt composition.
82 . The process of claim 80 , wherein in step (b) the mixture is exposed to hydrogenation reagents for at least about 4 hours.
83 . The process of claim 82 , wherein in step (b) the mixture is exposed to the hydrogenation reagents for at least about 5 hours.
84 . The process of claim 83 , wherein in step (b) the mixture is exposed to the hydrogenation reagents for about 21 hours.
85 . The process of claim 80 , wherein the second oxycodone salt composition contains less than about 25 ppm 14-hydroxycodeinone.
86 . The process of claim 85 , wherein the second oxycodone salt composition contains less than about 15 ppm 14-hydroxycodeinone.
87 . The process of claim 86 , wherein the second oxycodone salt composition contains less than about 10 ppm 14-hydroxycodeinone.
88 . The process of claim 87 , wherein the second oxycodone salt composition contains less than about 5 ppm 14-hydroxycodeinone.
89 . The process of claim 80 , wherein at least some of 8α,14-dihydroxy-7,8-dihydrocodeinone in the oxycodone free base composition is converted to 14-hydroxycodeinone by an acid catalyzed dehydration consisting of conversion of 8α,14-dihydroxy-7,8-dihydrocodeinone to 14-hydroxycodeinone during step (b).
90 . The process of claim 80 , comprising preferentially removing 14-hydroxycodeinone from the first oxycodone salt composition or the second oxycodone salt composition.
91 . The process of claim 90 , wherein the 14-hydroxycodeinone is preferentially removed by exposing the first oxycodone salt composition or the second oxycodone salt composition to a substance that preferentially removes the 14-hydroxycodeinone compared to the oxycodone.
92 . The process of claim 91 , wherein the substance is a gel.
93 . The process of claim 91 , wherein the first oxycodone salt composition is passed through the substance that preferentially removes the 14-hydroxycodeinone.
94 . The process of claim 91 , wherein a slurry is formed with the oxycodone salt and the substance that preferentially removes the 14-hydroxycodeinone.
95 . The process of claim 91 , wherein step (c) is carried out at a temperature between about 40° C. to about 85° C.
96 . The process of claim 80 , comprising incubating the oxycodone free base composition comprising 8α,14-dihydroxy-7,8-dihydrocodeinone under conditions suitable to convert the oxycodone free base to the first oxycodone salt composition, wherein said conditions promote an acid catalyzed dehydration consisting of conversion of the 8α,14-dihydroxy-7,8-dihydrocodeinone to 14-hydroxycodeinone.
97 . The process of claim 80 , comprising isolating the second oxycodone salt composition.
98 . The process of claim 80 , wherein the second oxycodone salt composition comprises less than 100 ppm 14-hydroxycodeinone.
100 . The process of claim 98 , wherein the second oxycodone composition comprises less than 25 ppm of 14-hydroxycodeinone.
100 . The process of claim 100 , wherein the second oxycodone composition comprises less than 10 ppm of 14-hydroxycodeinone.
101 . The process of claim 98 , wherein the oxycodone salt composition comprises 1 ppm or more 14-hydroxycodeinone.
102 . A process for preparing an oxycodone salt composition, which process comprises steps of:
(a) hydrogenating a 14-hydroxycodeinone composition to obtain an oxycodone free base composition comprising 8α,14-dihydroxy-7,8-dihydrocodeinone;
(b) converting the oxycodone free base composition comprising 8α,14-dihydroxy-7,8-dihydrocodeinone to an oxycodone salt composition comprising an amount of 14-hydroxycodeinone; and
(c) hydrogenating the first oxycodone salt composition to a second oxycodone salt composition comprising a decreased amount of 14-hydroxycodeinone.
103 . The process of claim 102 , wherein the decreased amount is less than 100 ppm.
104 . The process of claim 103 , wherein the decreased amount is less than 25 ppm.
105 . The process of claim 104 , wherein the decreased amount is less than 10 ppm.
106 . The process of claim 103 , wherein the second oxycodone salt composition comprises 1 ppm or more 14-hydroxycodeinone.
107 . The process of claim 102 , comprising isolating the second oxycodone salt composition.
108 . The process of claim 102 , wherein the process is for preparing an oxycodone hydrochloride salt composition comprising less than 25 ppm 14-hydroxycodeinone.
109 . The process of claim 108 , wherein the oxycodone salt composition comprises 1 ppm or more 14-hydroxycodeinone.