Process of preparing low ABUK oxymorphone hydrochloride
View Patent ↗An improved method for the preparation of the low ABUK oxymorphone hydrochloride is provided. The oxymorphone hydrochloride is produced by hydrogenating a starting material comprising oxymorphone base and 14-hydroxymorphinone in a mixture comprising an alcohol, water and an acid, removing some of the water and adding more alcohol to the mixture.
1. A process for preparing an oxymorphone hydrochloride composition having less than 10 ppm of 14-hydroxymorphinone comprising:
(i) hydrogenating an oxymorphone base composition having more than 10 ppm of 14-hydroxymorphinone in a mixture comprising 1-propanol, water and an acid;
(ii) removing a portion of the 1-propanol and water in step (i) to reduce the water content of the mixture; and
(iii) adding alcohol to the mixture.
2. The process of claim 1 , wherein the hydrogenating step includes the use of gaseous hydrogen.
3. The process of claim 1 , wherein the acid is hydrochloric acid.
4. The process of claim 3 , wherein the hydrochloric acid is concentrated hydrochloric acid.
5. The process of claim 3 , wherein the hydrochloric acid is diluted hydrochloric acid.
6. The process of claim 1 , wherein the acid is a solution of hydrogen chloride in an alcohol.
7. The process of claim 1 , wherein the portion of the 1-propanol and water in step (i) is removed by distillation.
8. The process of claim 7 , wherein the distillation is under vacuum.
9. The process of claim 1 , wherein the process occurs at an elevated temperature.
10. The process of claim 7 , wherein the process occurs under reflux.
11. The process of claim 9 , wherein the elevated temperature is about 45° C. to about 65° C.
12. The process of claim 1 , wherein the water content is reduced to about less than 10% by Karl Fischer titration.
13. The process of claim 1 , wherein the oxymorphone hydrochloride is Form I and at least 99.9% pure as measured by HPLC.
14. The process of claim 1 , wherein the oxymorphone hydrochloride is Form II and at least 99.9% pure as measured by HPLC.
15. A pharmaceutical formulation comprising at least one pharmaceutically acceptable excipient and oxymorphone hydrochloride according to claim 1 .
16. The pharmaceutical formulation according to claim 15 , wherein the formulation is a tamper resistant or abuse proof dosage form.
17. The pharmaceutical formulation according to claim 15 , wherein the formulation is an extended release or sustained release dosage form.
18. A method of treating pain comprising administering a pharmaceutical formulation according to claim 15 to a patient in need thereof.
19. A process for preparing an oxymorphone hydrochloride composition having less than 10 ppm of 14-hydroxymorphinone comprising:
(i) hydrogenating an oxymorphone base composition having more than 10 ppm of 14-hydroxymorphinone in a mixture comprising an alcohol, water and an acid;
(ii) removing a portion of the alcohol and water in step (i) to reduce the water content of the mixture; and
(iii) adding 1-propanol to the mixture.