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 14-hydroxycodeinone, which process comprises steps of:
(a) oxidizing a thebaine composition to form a 14-hydroxycodeinone composition, the oxidizing being performed at a suitable pH to decrease the production of 8α,14-dihydroxy-7,8-dihydrocodeinone in the 14-hydroxycodeinone composition;
(b) hydrogenating the 14-hydroxycodeinone composition to form an oxycodone base composition; and
(c) converting the oxycodone base composition to the oxycodone salt composition comprising 14-hydroxycodeinone.
81 . The process of claim 80 , comprising forming a solution comprising hydrochlorides of oxycodone, 8α,14-dihydroxy-7,8-dihydrocodeinone and 14-hydroxycodeinone during the process.
82 . The process of claim 81 , comprising adding a basic agent to the solution to decrease the rate of dehydration of 8α,14-dihydroxy-7,8-dihydrocodeinone to 14-hydroxycodeinone.
83 . The process of claim 82 , wherein the basic agent is sodium hydroxide.
84 . The process of claim 80 , wherein the oxycodone salt composition is substantially free of 14-hydroxycodeinone.
85 . The process of claim 84 , wherein the oxycodone salt composition comprises less than 100 ppm 14-hydroxycodeinone.
86 . The process of claim 85 , wherein the oxycodone salt composition comprises less than 25 ppm 14-hydroxycodeinone.
87 . The process of claim 86 , wherein the oxycodone salt composition comprises less than 15 ppm 14-hydroxycodeinone.
88 . The process of claim 87 , wherein the oxycodone salt composition comprises less than 10 ppm 14-hydroxycodeinone.
89 . The process of claim 88 , wherein the oxycodone salt composition comprises less than 5 ppm 14-hydroxycodeinone.
90 . The process of claim 85 , wherein the oxycodone salt composition comprises 0.25 ppm or more 14-hydroxycodeinone.
91 . The process of claim 85 , wherein the oxycodone salt composition comprises 1 ppm or more 14-hydroxycodeinone.
92 . The process of claim 85 , wherein the oxycodone salt composition comprises 5 ppm or more 14-hydroxycodeinone.
93 . The process of claim 80 , wherein the oxycodone base composition comprises 8α,14-dihydroxy-7,8-dihydrocodeinone.
94 . The process of claim 93 , wherein at least some of the 8α,14-dihydroxy-7,8-dihydrocodeinone 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 (c).
95 . The process of claim 80 , wherein the process is for preparing an oxycodone hydrochloride salt composition.
96 . The process of claim 80 , wherein the process is for preparing an oxycodone hydrochloride salt active pharmaceutical ingredient composition.
97 . A process for preparing an oxycodone salt composition comprising 14-hydroxycodeinone, which process comprises steps of:
(a) oxidizing a thebaine composition to form a 14-hydroxycodeinone composition, the oxidizing being performed at a suitable pH to minimize or eliminate the production of 8α,14-dihydroxy-7,8-dihydrocodeinone in the 14-hydroxycodeinone composition;
(b) hydrogenating the 14-hydroxycodeinone composition to form an oxycodone base composition;
(c) converting the oxycodone base composition to the oxycodone salt composition, and
(d) analyzing a sample of the oxycodone salt composition for the presence of 14-hydroxycodeinone.
98 . The process of claim 97 , wherein the oxycodone salt composition is substantially free of 14-hydroxycodeinone.
99 . The process of claim 98 , wherein the oxycodone salt composition comprises greater than 100 ppm 14-hydroxycodeinone.
100 . The process of claim 99 , comprising further hydrogenating the oxycodone salt composition comprising greater than 100 ppm 14-hydroxycodeinone to decrease the level of 14-hydroxycodeinone.
101 . The process of claim 100 , wherein the level of 14-hydroxycodeinone is decreased to less than 100 ppm.
102 . The process of claim 101 , wherein the level of 14-hydroxycodeinone is decreased to less than 25 ppm.
103 . The process of claim 102 , wherein the level of 14-hydroxycodeinone is decreased to less than 15 ppm.
104 . The process of claim 103 , wherein the level of 14-hydroxycodeinone is decreased to less than 10 ppm.
105 . The process of claim 99 , wherein the oxycodone salt composition comprises 1 ppm or more 14-hydroxycodeinone.
106 . The process of claim 97 , wherein the oxycodone base composition comprises 8α,14-dihydroxy-7,8-dihydrocodeinone.
107 . The process of claim 106 , wherein at least some of the 8α,14-dihydroxy-7,8-dihydrocodeinone 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 (c).
108 . The process of claim 97 , wherein the process is for preparing an oxycodone hydrochloride salt composition.
109 . The process of claim 97 , wherein the process is for preparing an oxycodone hydrochloride salt active pharmaceutical ingredient composition.