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 comprising less than 100 ppm 14-hydroxycodeinone, which process comprises steps of:
(a) titrating an oxycodone base composition comprising 8α,14-dihydroxy-7,8-dihydrocodeinone with an acid under conditions sufficient to provide an oxycodone salt composition comprising less than 100 ppm 14-hydroxycodeinone; and
(b) isolating the oxycodone salt composition comprising less than 100 ppm 14-hydroxycodeinone.
81 . The process of claim 80 , wherein the conditions affect acid catalyzed dehydration consisting of conversion of the 8α,14-dihydroxy-7,8-dihydrocodeinone to 14-hydroxycodeinone.
82 . The process of claim 81 , wherein the conditions reduce the rate of dehydration of the 8α,14-dihydroxy-7,8-dihydrocodeinone to the 14-hydroxycodeinone.
83 . The process of claim 80 , wherein at least some of the 8α,14-dihydroxy-7,8-dihydrocodeinone is dehydrated to 14-hydroxycodeinone during the process.
84 . The process of claim 82 , comprising preferentially removing at least some of the 14-hydroxycodeinone.
85 . The process of claim 80 , wherein the acid comprises hydrochloric acid.
86 . The process of claim 80 , wherein step (a) is performed under reducing conditions.
87 . The process of claim 80 , wherein the process is for preparing an oxycodone hydrochloride salt composition.
88 . The process of claim 80 , wherein the process is for preparing an oxycodone hydrochloride active pharmaceutical ingredient composition.
89 . The process of claim 80 , wherein the oxycodone salt composition is isolated by a process comprising crystallization.
90 . The process of claim 80 , wherein the oxycodone salt composition in step (a) comprises 0.25 ppm or more 14-hydroxycodeinone.
91 . The process of claim 80 , wherein the oxycodone salt composition in step (a) comprises 1 ppm or more 14-hydroxycodeinone.
92 . The process of claim 80 , wherein the oxycodone salt composition in step (a) comprises 5 ppm or more 14-hydroxycodeinone.
93 . A process for preparing an oxycodone salt composition, which process comprises steps of:
(a) titrating an oxycodone base composition comprising 8α,14-dihydroxy-7,8-dihydrocodeinone with an acid under conditions sufficient to provide an oxycodone salt composition that is substantially free of 14-hydroxycodeinone; and
(b) isolating the oxycodone salt composition that is substantially free of 14-hydroxycodeinone.
94 . The process of claim 93 , wherein the conditions affect acid catalyzed dehydration consisting of conversion of the 8α,14-dihydroxy-7,8-dihydrocodeinone to 14-hydroxycodeinone.
95 . The process of claim 94 , wherein the conditions reduce the rate of dehydration of the 8α,14-dihydroxy-7,8-dihydrocodeinone to the 14-hydroxycodeinone.
96 . The process of claim 93 , wherein at least some of the 8α,14-dihydroxy-7,8-dihydrocodeinone is dehydrated to 14-hydroxycodeinone during the process.
97 . The process of claim 96 , comprising preferentially removing at least some of the 14-hydroxycodeinone.
98 . The process of claim 93 , wherein the acid comprises hydrochloric acid.
99 . The process of claim 93 , wherein step (a) is performed under reducing conditions.
100 . The process of claim 93 , wherein the process is for preparing an oxycodone hydrochloride salt composition.
101 . The process of claim 93 , wherein the process is for preparing an oxycodone hydrochloride active pharmaceutical ingredient composition.
102 . The process of claim 93 , wherein the oxycodone salt composition is isolated by a process comprising crystallization.
103 . The process of claim 93 , wherein the isolated oxycodone salt composition comprises less than 25 ppm 14-hydroxycodeinone.
104 . The process of claim 103 , wherein the isolated oxycodone salt composition comprises less than 15 ppm 14-hydroxycodeinone.
105 . The process of claim 104 , wherein the isolated oxycodone salt composition comprises less than 10 ppm 14-hydroxycodeinone.
106 . The process of claim 93 , wherein the isolated oxycodone salt composition comprises 0.25 ppm or more 14-hydroxycodeinone.
107 . The process of claim 106 , wherein the oxycodone salt composition comprises 0.5 ppm or more 14-hydroxycodeinone.
108 . The process of claim 107 , wherein the oxycodone salt composition comprises 1 ppm or more 14-hydroxycodeinone.
109 . The process of claim 108 , wherein the oxycodone salt composition comprises 5 ppm or more 14-hydroxycodeinone.