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 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.