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 composition comprising 8α,14-dihydroxy-7,8-dihydrocodeinone and 14-hydroxycodeinone comprising:
combining an oxycodone free base and an acid to form a mixture,
analyzing a sample of the mixture for the presence of 8α,14-dihydroxy-7,8-dihydrocodeinone and 14-hydroxycodeinone, and
isolating an oxycodone composition comprising 8α,14-dihydroxy-7,8-dihydrocodeinone and 14-hydroxycodeinone from the mixture by crystallization and filtration.
81 . The process of claim 80 , wherein the isolated oxycodone composition is substantially free of 14-hydroxycodeinone.
82 . The process of claim 80 , wherein the isolated composition comprises greater than 100 ppm 14-hydroxycodeinone.
83 . The process of claim 81 , further comprising hydrogenating the isolated oxycodone composition to decrease the level of 14-hydroxycodeinone.
84 . A process for preparing an oxycodone composition comprising 8α,14-dihydroxy-7,8-dihydrocodeinone and 14-hydroxycodeinone comprising:
combining an oxycodone free base and hydrochloric acid to form a mixture, isolating an oxycodone composition from the mixture, and
analyzing a sample of the oxycodone composition for the presence of 8α,14-dihydroxy-7,8-dihydrocodeinone and 14-hydroxycodeinone.
85 . The process of claim 84 , wherein the mixture comprises an alcohol.
86 . The process of claim 84 , wherein the mixture comprises a catalyst.
87 . The process of claim 86 , wherein the catalyst is Pd/C catalyst.
88 . The process of claim 84 , wherein the mixture is heated.
89 . The process of claim 88 , wherein the mixture is heated to 75° C.
90 . The process of claim 84 , wherein the oxycodone hydrochloride active pharmaceutical ingredient is isolated by crystallization and filtration.
91 . The process of claim 84 , further comprising analyzing a sample of the mixture for the presence of 8α,14-dihydroxy-7,8-dihydrocodeinone and 14-hydroxycodeinone.
92 . The process of claim 84 , wherein the sample is analyzed by HPLC.
93 . The process of claim 92 , wherein the level of 14-hydroxycodeinone in the sample is less than 25 ppm.
94 . The process of claim 93 , wherein the level of 14-hydroxycodeinone is less than about 15 ppm.
95 . The process of claim 94 , wherein the level of 14-hydroxycodeinone is less than about 10 ppm.
96 . The process of claim 95 , wherein the level of 14-hydroxycodeinone is less than about 5 ppm.
97 . The process of claim 84 , wherein the level of 14-hydroxycodeinone is greater than 100 ppm 14-hydroxycodeinone.
98 . The process of claim 97 , further comprising hydrogenating the oxycodone composition comprising greater than 100 ppm 14-hydroxycodeinone to decrease the level of 14-hydroxycodeinone.
99 . The process of claim 84 , wherein the process is for preparing an oxycodone salt composition.
100 . The process of claim 99 , wherein the process is for preparing an oxycodone hydrochloride salt composition.
101 . The process of claim 100 , wherein the process is for preparing an oxycodone hydrochloride active pharmaceutical ingredient composition.
102 . A process for preparing an oxycodone hydrochloride composition comprising 8α,14-dihydroxy-7,8-dihydrocodeinone and 14-hydroxycodeinone comprising:
reacting an oxycodone base composition with an acid having a higher pH than hydrochloric acid to form a corresponding acid addition salt of oxycodone, converting the acid addition salt of oxycodone to the oxycodone hydrochloride composition,
and sampling levels of 8α,14-dihydroxy-7,8-dihydrocodeinone and 14-hydroxycodeinone in the oxycodone hydrochloride composition.
103 . The process of claim 102 , wherein the oxycodone hydrochloride composition is substantially free from 14-hydroxycodeinone.
104 . The process of claim 103 , wherein the oxycodone hydrochloride composition comprises less than 100 ppm 14-hydroxycodeinone.
105 . The process of claim 102 , wherein the oxycodone hydrochloride composition comprises greater than 100 ppm 14-hydroxycodeinone.
106 . The process of claim 105 , further comprising hydrogenating the oxycodone hydrochloride composition comprising greater than 100 ppm 14-hydroxycodeinone to decrease the level of 14-hydroxycodeinone.
107 . The process of claim 106 , wherein the oxycodone hydrochloride composition is oxycodone hydrochloride active pharmaceutical ingredient.
108 . The process of claim 102 , wherein the acid having a higher pH than hydrochloric acid is selected from the group consisting of tartaric acid, oxalic acid, fumaric acid, phosphoric acid, sulfuric acid, and mixtures thereof.
109 . The process of claim 104 , wherein the oxycodone hydrochloride composition comprises at least 1 ppm 14-hydroxycodeinone.