Granted Patent B2

US 9,777,011 · App. 15/058,420 · Granted Oct 3, 2017

Inventors: Robert Chapman (Downingtown, PA); Lonn S. Rider (Foster, RI); Qi Hong (Sharon, MA); Donald Kyle (Yardley, PA); Robert Kupper (East Greenwich, RI)

Assignees: PURDUE PHARMA L.P.; THE P.F. LABORATORIES, INC.; PURDUE PHARMACEUTICALS L.P.; RHODES TECHNOLOGIES

C07D489/08A61K9/14A61K9/20A61K9/2095A61K9/48A61K9/4833A61K31/485C07D489/02C07D489/04

Abstract

Claims (27)

1. A process for purifying a starting composition comprising: (a) oxycodone free base, oxycodone HCl or a mixture thereof, and (b) 14-hydroxycodeinone, comprising subjecting the composition to a hydrogenation reaction one or more times at a temperature between 40° C. and 100° C., wherein (i) each hydrogenation reaction is carried out for a time from 4 hours to 36 hours, and (ii) the total reaction time of all of the hydrogenation reactions is from 10 hours to 36 hours.

2. A process of claim 1 , wherein the starting composition comprises oxycodone free base and 14-hydroxycodeinone.

3. The process of claim 2 , wherein the starting composition further comprises 8α,14-dihydroxy-7,8-dihydrocodeinone.

4. A process of claim 3 , wherein the starting composition is subjected to conditions that promote an acid catalyzed dehydration of 8α,14-dihydroxy-7,8-dihydrocodeinone to 14-hydroxycodeinone, prior to or during one or more of the hydrogenation reactions.

5. The process of claim 4 , wherein 400 ppm or less of 8α,14-dihydroxy-7,8-dihydrocodeinone is present at the end of all of the hydrogenation reactions.

6. The process of claim 2 , wherein at least one of the hydrogenation reactions is carried out at a temperature from 40° C. to 85° C.

7. The process of claim 2 , wherein at least one of the hydrogenation reactions is carried out at a temperature from 75° C. to 85° C.

8. The process of claim 2 , wherein at least one of the hydrogenation reactions is carried out for a time from 4 hours to 10 hours.

9. The process of claim 2 , wherein at least one of the hydrogenation reactions is carried out for a time from 10 hours to 21.7 hours.

10. The process of claim 9 , wherein the hydrogenation reaction or reactions that are carried out for a time from 10 hours to 21.7 hour are carried out at a temperature from 75° C. to 85° C.

11. The process of claim 2 , wherein at least one of the hydrogenation reactions is carried out for a time from 21.7 hours to 36 hours.

12. The process of claim 2 , wherein the hydrogenation reaction is carried out more than one time.

13. The process of claim 2 , wherein less than 100 ppm of 14-hydroxycodeinone is present at the end of all of the hydrogenation reactions.

14. The process of claim 2 , wherein less than 10 ppm of 14-hydroxycodeinone is present at the end of all of the hydrogenation reactions.

15. A process of claim 1 , wherein the starting composition comprises oxycodone HCl and 14-hydroxycodeinone.

16. The process of claim 15 , wherein the starting composition further comprises 8α,14-dihydroxy-7,8-dihydrocodeinone.

17. The process of claim 16 , wherein 400 ppm or less of 8α,14-dihydroxy-7,8-dihydrocodeinone is present at the end of all of the hydrogenation reactions.

18. The process of claim 15 , wherein at least one of the hydrogenation reactions is carried out at a temperature from 40° C. to 85° C.

19. The process of claim 15 , wherein at least one of the hydrogenation reactions is carried out at a temperature from 75° C. to 85° C.

20. The process of claim 15 , wherein at least one of the hydrogenation reactions is carried out for a time from 4 hours to 10 hours.

21. The process of claim 15 , wherein at least one of the hydrogenation reactions is carried out for a time from 10 hours to 21.7 hours.

22. The process of claim 21 wherein the hydrogenation reaction or reactions that are carried out for a time from 10 hours to 21.7 hour are carried out at a temperature from 75° C. to 85° C.

23. The process of claim 15 , wherein at least one of the hydrogenation reactions is carried out for a time from 21.7 hours to 36 hours.

24. The process of claim 15 , wherein the hydrogenation reaction is carried out more than one time.

25. The process of claim 15 , wherein less than 100 ppm of 14-hydroxycodeinone is present at the end of all of the hydrogenation reactions.

26. The process of claim 15 , wherein less than 10 ppm of 14-hydroxycodeinone is present at the end of all of the hydrogenation reactions.

27. The process of claim 1 , wherein at least 1 kg of the crystalline oxycodone HCl is prepared.

Assignments (4)

Continuity (13)