Process for preparing oxycodone compositions
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. A process of purifying oxycodone free base or oxycodone HCl that contains 8α,14-dihydroxy-7,8-dihydrocodeinone or HCl salt thereof, said process comprising:
(i) reducing the amount of 8α,14-dihydroxy-7,8-dihydrocodeinone or HCl salt thereof in the oxycodone free base or oxycodone HCl;
(ii) dissolving the resultant oxycodone free base or oxycodone HCl from step (i) in a suitable recrystallization solvent;
(iii) cooling the recrystallization solvent to precipitate purified oxycodone free base or oxycodone HCl; and
(iv) recovering the purified oxycodone free base or oxycodone HCl.
2. The process of claim 1 , wherein the ratio of 8α,14-dihydroxy-7,8-dihydrocodeinone or HCl salt thereof to oxycodone free base or oxycodone HCl following step (i) is 0.04% or less as measured by HPLC.
3. The process of claim 1 , wherein at least 1 kg of the oxycodone free base or oxycodone HCl is purified.
4. The process of claim 1 , wherein step (i) is carried out by hydrogenation.
5. The process of claim 4 , wherein the hydrogenation is carried out one or more times at a temperature between 40° C. and 85° C.
6. The process of claim 5 , wherein the hydrogenation step reduces the amount of 14-hydroxycodeinone in the oxycodone free base or oxycodone HCl.
7. The process of claim 6 , wherein less than 10 ppm of 14-hydroxycodeinone is present following step (iv).
8. The process of claim 6 , wherein no 14-hydroxycodeinone are present following step (iii).
9. The process of claim 4 , wherein step (i) is carried out in a solvent suitable for hydrogenation.
10. The process of claim 9 , wherein the hydrogenation reaction is carried out at a pH lower than 1.0.
11. The process of claim 10 , further comprising raising the pH of the reaction following step (i) or step (ii).
12. The process of claim 1 , wherein the hydrogenation is carried out for a time between 4 hours and 36 hours.
13. The process of claim 1 , wherein the starting oxycodone free base or oxycodone HCl was formed by hydrogenation of 14-hydoxycodienone.
14. The process of claim 2 , wherein the starting oxycodone free base or oxycodone HCl was formed by hydrogenation of 14-hydoxycodienone.
15. The process of claim 1 , wherein the process comprises purifying oxycodone free base.
16. The process of claim 1 , wherein the process comprises purifying oxycodone HCl.
17. The process of claim 2 , wherein the process comprises purifying oxycodone free base.
18. The process of claim 2 , wherein the process comprises purifying oxycodone HCl.
19. Purified oxycodone free base prepared according to the process of claim 2 , wherein the ratio of 8 α, 14-dihydroxy-7,8-dihydrocodeinone to oxycodone free base is 0.04% or less as measured by HPLC.
20. Purified oxycodone HCl prepared according to the process of claim 2 , wherein the ratio of 8 α, 14-dihydroxy-7,8-dihydrocodeinone HCl salt to oxycodone HCl is 0.04% or less as measured by HPLC.