Process for preparing oxycodone compositions
AssigneesPurdue Pharma L.P., The P.F. Laboratories, Inc., Purdue Pharmaceuticals L.P., Rhodes Technologies
InventorsRobert CHAPMAN, Lonn S. RIDER, Qi HONG, Donald KYLE, Robert KUPPER
Life of this patent
Estimating the term…
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.
Claims70
A process for preparing an oxycodone hydrochloride composition having less than 25 ppm 14-hydroxycodeinone comprising hydrogenating an oxycodone hydrochloride composition having at least 100 ppm 14-hydroxycodeinone in a suitable solvent to produce an oxycodone composition having less than 25 ppm 14-hydroxycodeinone.
A process for preparing an oxycodone hydrochloride composition having less than 25 ppm 14-hydroxycodeinone comprising reacting hydrochloric acid with an oxycodone free base composition in a solvent under conditions to form oxycodone hydrochloride having a 14-hydroxycodeinone level of less than 25 ppm.
A process for preparing an oxycodone hydrochloride composition having a 14-hydroxycodeinone level in an amount of less than 25 ppm comprising reacting in a suitable solvent an oxycodone base composition having an amount of 8,14-dihydroxy-7,8-dihydrocodeinone;
- with hydrochloric acid in an amount greater than 1.0 molar equivalent as compared to the oxycodone base composition to promote the dehydration of the 8,14-dihydroxy-7,8-dihydrocodeinone to 14-hydroxycodeinone to form an oxycodone hydrochloride composition having a 14-hydroxycodeinone level in an amount of less than 25 ppm;
- the reacting step being performed under reducing conditions to promote the conversion of 14-hydroxycodeinone to oxycodone.
A process for preparing an oxycodone hydrochloride composition having less than 25 ppm 14-hydroxycodeinone comprising
- titrating an oxycodone base composition comprising an amount of 8,14-dihydroxy-7,8-dihydrocodeinone with hydrochloric acid in order to reduce the amount of excess hydrochloric acid and minimize the dehydration of 8,14-dihydroxy-7,8-dihydrocodeinone to 14-hydroxycodeinone during formation of the oxycodone hydrochloride composition having less than 25 ppm 14-hydroxycodeinone.
A process for preparing an oxycodone hydrochloride composition having a 14-hydroxycodeinone level in an amount of less than 25 ppm comprising
- reacting in a suitable solvent an oxycodone base composition with hydrochloric acid in an amount greater than 1.0 molar equivalent as compared to the oxycodone base composition, the reacting step being performed under reducing conditions, to form an oxycodone hydrochloride composition having a 14-hydroxycodeinone level in an amount of less than 25 ppm.
A process for preparing an oxycodone hydrochloride composition having less than 25 ppm 14-hydroxycodeinone comprising
- hydrogenating a 14-hydroxycodeinone composition to obtain an oxycodone free base composition;
- converting the oxycodone free base composition to oxycodone hydrochloride;
- and
- hydrogenating the oxycodone hydrochloride to obtain an oxycodone composition having less than 25 ppm 14-hydroxycodeinone.
A process for preparing an oxycodone hydrochloride composition having less than 25 ppm 14-hydroxycodeinone comprising
- hydrogenating a 14-hydroxycodeinone composition to obtain an oxycodone free base composition;
- converting the oxycodone free base composition to oxycodone hydrochloride;
- isolating the oxycodone hydrochloride;
- and
- hydrogenating the oxycodone hydrochloride to obtain an oxycodone composition having less than 25 ppm 14-hydroxycodeinone.
A process for preparing an oxycodone hydrochloride composition having less than 25 ppm 14-hydroxycodeinone comprising
- oxidizing a thebaine composition to form 14-hydroxycodeinone composition, said oxidizing being performed at a suitable pH to minimize or eliminate the production of 8,14-dihydroxy-7,8-dihydrocodeinone in said 14-hydroxycodeinone composition;
- hydrogenating said 14-hydroxycodeinone composition to form an oxycodone base composition;
- and
- converting said oxycodone base composition to an oxycodone hydrochloride composition having less than 25 ppm 14-hydroxycodeinone.
A process for preparing 14-hydroxycodeinone comprising
- oxidizing a thebaine composition to form 14-hydroxycodeinone composition, said oxidizing being performed at a suitable pH to minimize or eliminate the production of 8,14-dihydroxy-7,8-dihydrocodeinone in said 14-hydroxycodeinone composition;
A process for preparing an oxycodone hydrochloride composition 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, and
- converting said acid addition salt of oxycodone to oxycodone hydrochloride.
A process for preparing an oxycodone hydrochloride composition having a 14-hydroxycodeinone level in an amount of less than 25 ppm comprising
- contacting an oxycodone base composition having an amount of 8,14-dihydroxy-7,8-dihydrocodeinone with a substance that preferentially removes the 8,14-dihydroxy-7,8-dihydrocodeinone as compared to the oxycodone base;
- and
- converting said oxycodone base composition to an oxycodone hydrochloride composition having less than 25 ppm 14-hydroxycodeinone.
A process for preparing an oxycodone hydrochloride composition having a 14-hydroxycodeinone level in an amount of less than 25 ppm comprising
- subjecting an oxycodone base composition having an amount of 8,14-dihydroxy-7,8-dihydrocodeinone to chromatographic separation to preferentially removes the 8,14-dihydroxy-7,8-dihydrocodeinone as compared to the oxycodone base;
- and
- converting said oxycodone base composition to an oxycodone hydrochloride composition having less than 25 ppm 14-hydroxycodeinone.
A process for preparing an oxycodone hydrochloride composition having a 14-hydroxycodeinone level in an amount of less than 25 ppm comprising
- contacting an oxycodone hydrochloride composition having an amount of 14-hydroxycodeinone with a substance that preferentially removes the 14-hydroxycodeinone as compared to the oxycodone hydrochloride;
- and
- recovering an oxycodone hydrochloride composition having less than 25 ppm 14-hydroxycodeinone.
A process for preparing an oxycodone hydrochloride composition having a 14-hydroxycodeinone level in an amount of less than 25 ppm comprising
- subjecting an oxycodone hydrochloride composition having an amount of 14-hydroxycodeinone to chromatographic separation to preferentially removes the 14-hydroxycodeinone as compared to the oxycodone hydrochloride;
- and
- recovering oxycodone hydrochloride composition having less than 25 ppm 14-hydroxycodeinone.
A process for preparing an oxycodone hydrochloride composition having a 14-hydroxycodeinone level in an amount of less than 25 ppm comprising
- reacting in a suitable solvent an oxycodone base composition having an amount of 8,14-dihydroxy-7,8-dihydrocodeinone, with boronated polystyrene resin;
- and
- converting said oxycodone base composition to an oxycodone hydrochloride composition having less than 25 ppm 14-hydroxycodeinone.
A process for preparing an oxycodone hydrochloride composition comprising
- reacting in a suitable solvent an oxycodone base composition with boronated polystyrene resin;
- and
- converting said oxycodone base composition to an oxycodone hydrochloride composition.
A process for preparing an oxycodone hydrochloride composition having a 14-hydroxycodeinone level in an amount of less than 25 ppm comprising
- combining hydrochloric acid and an oxycodone base composition having an amount of 8,14-dihydroxy-7,8-dihydrocodeinone in a solvent to form a solution;
- and
- spray drying said solution to generate oxycodone hydrochloride composition having a 14-hydroxycodeinone level in an amount of less than 25 ppm.
A process for preparing an oxycodone hydrochloride composition having a 14-hydroxycodeinone level in an amount of less than 25 ppm comprising
- combining hydrochloric acid and an oxycodone base composition having an amount of 8,14-dihydroxy-7,8-dihydrocodeinone in a solvent to form a solution;
- and
- lyophilizing said solution to generate oxycodone hydrochloride composition having a 14-hydroxycodeinone level in an amount of less than 25 ppm.
A process for preparing an oxycodone hydrochloride composition comprising
- combining hydrochloric acid and an oxycodone base composition in a solvent to form a solution;
- and
- spray drying said solution to generate oxycodone hydrochloride.
A process for preparing an oxycodone hydrochloride composition comprising
- combining hydrochloric acid and an oxycodone base composition in a solvent to form a solution;
- and
- lyophilizing said solution to generate oxycodone hydrochloride.
Dependencies are inferred from the claim text.