Process for preparing oxycodone compositions

Abstract

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.