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:
salting an oxycodone free base composition comprising 8α,14-dihydroxy-7,8-dihydrocodeinone and 14-hydroxycodeinone to convert the oxycodone free base composition to an oxycodone salt composition,
promoting dehydration of 8α,14-dihydroxy-7,8-dihydrocodeinone to 14-hydroxycodeinone during the salting by overloading the amount of an acid during the conversion,
providing reducing conditions sufficient for the 14-hydroxycodeinone to be reduced to oxycodone,
isolating the oxycodone salt composition, and
analyzing a sample of the oxycodone salt composition for the presence of 8α,14-dihydroxy-7,8-dihydrocodeinone and 14-hydroxycodeinone.
81 . The process of claim 80 , wherein the reducing conditions sufficient for the 14-hydroxycodeinone to be reduced to oxycodone are provided by a catalyst and a hydrogen donor.
82 . The process of claim 81 , wherein the hydrogen donor is selected from the group consisting of hydrogen gas, formic acid, indoline, cyclohexene, sodium borohydride, tetrahydroquinoline, 2,5-dihydrofuran, phosphoric acid, and combinations thereof.
83 . The process of claim 81 , wherein the catalyst is selected from the group consisting of Raney cobalt, Raney nickel, palladium on carbon, platinum on carbon, palladium on alumina, platinum oxide, ruthenium on alumina, rhodium on alumina, and rhodium on carbon.
84 . The process of claim 81 , wherein the catalyst is a noble metal catalyst.
85 . The process of claim 81 , wherein the catalyst a palladium-carbon catalyst.
86 . The process of claim 80 , wherein the oxycodone salt composition comprises less than 25 ppm of 14-hydroxycodeinone.
87 . The process of claim 86 , wherein the oxycodone salt composition comprises less than 15 ppm of 14-hydroxycodeinone.
88 . The process of claim 87 , wherein the oxycodone salt composition comprises less than 10 ppm of 14-hydroxycodeinone.
89 . The process of claim 80 , wherein the oxycodone salt composition comprises less than 5 ppm of 14-hydroxycodeinone.
90 . The process of claim 80 , wherein the oxycodone salt composition is isolated by a process comprising crystallization.
91 . The process of claim 80 , wherein the acid is hydrochloric acid.
92 . The process of claim 80 , wherein the process is for preparing an oxycodone hydrochloride salt composition.
93 . The process of claim 92 , wherein the process is for preparing an oxycodone hydrochloride active pharmaceutical ingredient composition.
94 . A process for preparing an oxycodone salt composition comprising:
salting an oxycodone free base composition comprising 8α,14-dihydroxy-7,8-dihydrocodeinone and 14-hydroxycodeinone to convert the oxycodone free base composition to an oxycodone salt composition,
promoting dehydration of 8α,14-dihydroxy-7,8-dihydrocodeinone to 14-hydroxycodeinone during the salting by overloading the amount of an acid during the conversion,
providing reducing conditions sufficient for the 14-hydroxycodeinone to be reduced to oxycodone,
isolating the oxycodone salt composition, and
analyzing a sample of the oxycodone salt composition for the presence of 8α,14-dihydroxy-7,8-dihydrocodeinone and 14-hydroxycodeinone,
wherein the sample of the oxycodone salt composition comprises greater than 100 ppm 14-hydroxycodeinone.
95 . The process of claim 94 , further comprising hydrogenating the oxycodone salt composition to decrease the level of 14-hydroxycodeinone.
96 . The process of claim 95 , wherein the level of 14-hydroxycodeinone is decreased to less than 100 pm.
97 . The process of claim 96 , wherein the level of 14-hydroxycodeinone is decreased to less than 25 ppm.
98 . The process of claim 97 , wherein the level of 14-hydroxycodeinone is decreased to less than 10 ppm.
99 . The process of claim 94 , wherein the acid is hydrochloric acid.
100 . The process of claim 94 , wherein the process is for preparing an oxycodone hydrochloride salt composition.
101 . The process of claim 94 , wherein the process is for preparing an oxycodone hydrochloride active pharmaceutical ingredient composition.
102 . The process of claim 94 , wherein the process is for preparing an oxycodone hydrochloride active pharmaceutical ingredient composition comprising less than 25 ppm 14-hydroxycodeinone.
103 . A process for preparing an oxycodone salt composition comprising:
salting an oxycodone free base composition comprising 8α,14-dihydroxy-7,8-dihydrocodeinone and 14-hydroxycodeinone to convert the oxycodone free base composition to an oxycodone salt composition,
promoting dehydration of 8α,14-dihydroxy-7,8-dihydrocodeinone to 14-hydroxycodeinone during the salting by overloading the amount of an acid during the conversion,
providing reducing conditions sufficient for the 14-hydroxycodeinone to be reduced to oxycodone,
isolating the oxycodone salt composition, and
analyzing a sample of the oxycodone salt composition for the presence of 8α,14-dihydroxy-7,8-dihydrocodeinone and 14-hydroxycodeinone,
wherein the oxycodone salt composition is substantially free of 14-hydroxycodeinone.
104 . The process of claim 103 , wherein the oxycodone salt composition comprises less than 100 ppm 14-hydroxycodeinone.
105 . The process of claim 104 , wherein the oxycodone salt composition comprises 0.25 ppm or more 14-hydroxycodeinone.
106 . The process of claim 105 , wherein the oxycodone salt composition comprises 1 ppm or more 14-hydroxycodeinone
107 . The process of claim 103 , wherein the acid is hydrochloric acid.
108 . The process of claim 103 , wherein the process is for preparing an oxycodone hydrochloride salt composition.
109 . The process of claim 103 , wherein the process is for preparing an oxycodone hydrochloride salt active pharmaceutical ingredient composition.