Process for preparing oxycodone compositions

• US 10,407,434 B2
• Filed: 01/30/2019
• Issued: 09/10/2019
• Est. Priority Date: 03/30/2004
• Status: Active Grant

• Current Assignee: Purdue Pharma L.P.
• Original Assignee: Purdue Pharma L.P.
• Inventors: Chapman, Robert, Rider, Lonn S., Hong, Qi, Kyle, Donald, Kupper, Robert
• Primary Examiner(s): Aulakh, Charanjit
• Application Number:
  US16/262,683
• Publication Number:
  US 20190161492A1
• Time in Patent Office: 223 Days
• Field of Search: 546 45, 546 44
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 9/14 Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles microspheres A61K9/16; microcapsules A61K9/50; nanocapsules, nanoparticles of the matrix type A61K9/51
• CPC Class Codes: A61K 9/20 Pills, tablets, discs, rods A61K9/0004, A61K9/0007, A61K9/0056, A61K9/0065 take precedence; for reconstitution of a drink A61K9/0095
• CPC Class Codes: A61K 9/2095 Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing mechanical aspects A61J3/00
• CPC Class Codes: A61K 9/48 Preparations in capsules, e.g. of gelatin, of chocolate A61K9/0004 takes precedence; bite capsules A61K9/0056
• CPC Class Codes: A61K 9/4833 Encapsulating processes; Filling of capsules mechanical aspects A61J3/07
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: C07D 489/02 with oxygen atoms attached in positions 3 and 6, e.g. morphine, morphinone
• CPC Class Codes: C07D 489/04 Salts; Organic complexes
• CPC Class Codes: C07D 489/08 Oxygen atom

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.

Claims

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.