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 active pharmaceutical ingredient comprising:
dissolving an oxycodone composition comprising 8α,14-dihydroxy-7,8-dihydrocodeinone and a first amount of 14-hydroxycodeinone to form a solution;
exposing the solution to conditions that affect acid catalyzed dehydration consisting of conversion of the 8α,14-dihydroxy-7,8-dihydrocodeinone to 14-hydroxycodeinone; and
isolating an oxycodone active pharmaceutical ingredient comprising a second amount of 14-hydroxycodeinone by a process comprising crystallization, the second amount of 14-hydroxycodeinone being lower than the first amount of 14-hydroxycodeinone.
81 . The process of claim 80 , wherein the conditions reduce the rate of dehydration of the 8α,14-dihydroxy-7,8-dihydrocodeinone to 14-hydroxycodeinone.
82 . The process of claim 81 , wherein at least some of the 8α,14-dihydroxy-7,8-dihydrocodeinone is dehydrated to the 14-hydroxycodeinone during the process.
83 . The process of claim 82 , comprising preferentially removing at least some of the 14-hydroxycodeinone from the solution.
84 . The process of claim 80 , wherein the solution comprises an alcohol.
85 . The process of claim 84 , wherein the alcohol comprises isopropyl alcohol.
86 . The process of claim 84 , wherein the solution comprises a mixture comprising an alcohol and water.
87 . The process of claim 85 , wherein the solution comprises a mixture comprising isopropyl alcohol and water.
88 . The process of claim 80 , wherein the solution comprises an acid.
89 . The process of claim 88 , wherein the acid is formic acid.
90 . The process of claim 80 , wherein the process is for preparing an oxycodone hydrochloride salt active pharmaceutical ingredient.
91 . The process of claim 89 , wherein the oxycodone hydrochloride salt active pharmaceutical ingredient comprises less than 100 ppm of 14-hydroxycodeinone.
92 . The process of claim 91 , wherein the oxycodone hydrochloride salt active pharmaceutical ingredient comprises 1 ppm or more 14-hydroxycodeinone.
93 . A process for preparing an oxycodone active pharmaceutical ingredient comprising:
dissolving an oxycodone composition comprising 8α,14-dihydroxy-7,8-dihydrocodeinone and a first amount of 14-hydroxycodeinone to form a solution;
exposing the solution to conditions that affect acid catalyzed dehydration consisting of conversion of the 8α,14-dihydroxy-7,8-dihydrocodeinone to 14-hydroxycodeinone; and
isolating an oxycodone active pharmaceutical ingredient comprising a decreased amount of 14-hydroxycodeinone by a process comprising crystallization.
94 . The process of claim 93 , wherein the conditions reduce the rate of dehydration of the 8α,14-dihydroxy-7,8-dihydrocodeinone to 14-hydroxycodeinone.
95 . The process of claim 94 , 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 95 , wherein the solution comprises a catalyst.
97 . The process of claim 93 , wherein the solution comprises an alcohol.
98 . The process of claim 93 , wherein the decreased amount is less than 100 ppm.
99 . The process of claim 98 , wherein the alcohol comprises isopropyl alcohol.
100 . The process of claim 93 , wherein the solution comprises an acid.
101 . The process of claim 100 , wherein the acid is formic acid.
102 . The process of claim 93 , wherein the process is for preparing an oxycodone hydrochloride salt active pharmaceutical ingredient.
103 . The process of claim 102 , wherein the oxycodone hydrochloride salt active pharmaceutical ingredient comprises less than 100 ppm of 14-hydroxycodeinone.
104 . The process of claim 103 , wherein the oxycodone hydrochloride salt active pharmaceutical ingredient comprises 1 ppm or more 14-hydroxycodeinone.
105 . A process for preparing an oxycodone active pharmaceutical ingredient comprising:
adding an alcohol to a solution comprising oxycodone, 8α,14-dihydroxy-7,8-dihydrocodeinone and a first amount of 14-hydroxycodeinone; and
crystallizing an oxycodone active pharmaceutical ingredient comprising a second amount of 14-hydroxycodeinone;
wherein the second amount of 14-hydroxycodeinone is lower than the first amount of 14-hydroxycodeinone.
106 . The process of claim 105 , wherein the addition of alcohol affects an acid catalyzed dehydration consisting of conversion of the 8α,14-dihydroxy-7,8-dihydrocodeinone to 14-hydroxycodeinone.
107 . The process of claim 105 , wherein the oxycodone active pharmaceutical ingredient is an oxycodone salt active pharmaceutical ingredient.
108 . The process of claim 107 , wherein the oxycodone salt active pharmaceutical ingredient is an oxycodone hydrochloride salt active pharmaceutical ingredient.
109 . The process of claim 108 , wherein the oxycodone hydrochloride salt active pharmaceutical ingredient comprises less than 100 ppm of 14-hydroxycodeinone.