Oxycodone hydrochloride having less than 25 ppm 14-hydroxycodeinone

• US 7,674,799 B2
• Filed: 01/16/2007
• Issued: 03/09/2010
• Est. Priority Date: 03/30/2004
• Status: Active Grant

• Current Assignee: Purdue Pharma L.P.
• Original Assignee: Purdue Pharma L.P.
• Inventors: Hong, Qi, Kyle, Donald, Chapman, Robert, Kupper, Robert, Rider, Lonn S.
• Primary Examiner(s): AULAKH, CHARANJIT
• Application Number:
  US11/653,531
• Publication Number:
  US 20070117831A1
• Time in Patent Office: 1,148 Days
• Field of Search: 514/282, 546/45, 546/44
• US Class Current: 514/282
• 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. An oral dosage form comprising particles, the particles comprising from about 5 mg to about 320 mg oxycodone hydrochloride active pharmaceutical ingredient having less than 25 ppm 14-hydroxycodeinone, wherein at least a portion of the 14-hydroxycodeinone is derived from 8α

,14-dihydroxy-7,8-dihydrocodeinone during conversion of oxycodone free base to oxycodone hydrochloride, said particles being coated with an amount of hydrophobic material effective to provide a sustained release of the oxycodone hydrochloride when the coated particles are exposed to an aqueous solution.

4. The oral dosage form of claim 1, wherein the 14-hydroxycodeinone is derived solely from 8α

,14-dihydroxy-7,8-dihydrocodeinone.

8. The oral dosage form of claim 1, wherein the oxycodone hydrochloride active pharmaceutical ingredient has a lower limit of the 14-hydroxycodeinone of 0.25 ppm, 0.5 ppm, 1 ppm, 2 ppm or 5 ppm.

10. The oral dosage form of claim 8, which is a tablet or a capsule.

11. The oral dosage form of claim 8 comprising about 5 mg, about 10 mg, about 15 mg, about 20 mg, about 30 mg, about 40 mg, about 50 mg, about 60 mg, about 80 mg, about 100 mg, about 160 mg or about 320 mg of the oxycodone hydrochloride active pharmaceutical ingredient.

12. The oral dosage form of claim 8, comprising 10 mg, 15 mg, 20 mg, 30 mg, 40 mg, 60 mg, 80 mg or 160 mg of the oxycodone hydrochloride active pharmaceutical ingredient.

2. An oral dosage form comprising (i) from about 5 mg to about 320 mg of oxycodone hydrochloride active pharmaceutical ingredient having less than 25 ppm 14-hydroxycodeinone, wherein at least a portion of the 14-hydroxycodeinone is derived from 8α

,14-dihydroxy-7,8-dihydrocodeinone during conversion of oxycodone free base to oxycodone hydrochloride; and

(ii) a sustained release material, wherein the sustained release material is film coated onto said oxycodone hydrochloride active pharmaceutical ingredient.

5. The oral dosage form of claim 2, wherein the 14-hydroxycodeinone is derived solely from 8α

,14-dihydroxy-7,8-dihydrocodeinone.

9. The oral dosage form of claim 2, wherein the oxycodone hydrochloride active pharmaceutical ingredient has a lower limit of the 14-hydroxycodeinone is of 0.25 ppm, 0.5 ppm, 1 ppm, 2 ppm or 5 ppm.

13. The oral dosage form of claim 9, which is a tablet or a capsule.

14. The oral dosage form of claim 9 comprising about 5 mg, about 10 mg, about 15 mg, about 20 mg, about 30 mg, about 40 mg, about 50 mg, about 60 mg, about 80 mg, about 100 mg, about 160 mg or about 320 mg of the oxycodone hydrochloride active pharmaceutical ingredient.

15. The oral dosage form of claim 9 comprising 10 mg, 15 mg, 20 mg, 30 mg, 40 mg, 60 mg, 80 mg or 160 mg of the oxycodone hydrochloride active pharmaceutical ingredient.

3. An oral dosage form comprising:

(i) from about 5 mg to about 320 mg of oxycodone hydrochloride active pharmaceutical ingredient having less than 25 ppm 14-hydroxycodeinone, wherein at least a portion of the 14-hydroxycodeinone is derived from 8α

,14-dihydroxy-7,8-dihydrocodeinone during conversion of oxycodone free base to oxycodone hydrochloride; and

(ii) a pharmaceutically acceptable excipient.

6. The oral dosage form of claim 3, wherein the oxycodone hydrochloride active pharmaceutical ingredient has a lower limit of the 14-hydroxycodeinone of 0.25 ppm, 0.5 ppm, 1 ppm, 2 ppm or 5 ppm.

7. The oral dosage form of claim 3, wherein the 14-hydroxycodeinone is derived solely from 8α

,14-dihydroxy-7,8-dihydrocodeinone.

16. The oral dosage form of claim 6, which is a tablet or a capsule.

17. The oral dosage form of claim 6 comprising about 5 mg, about 10 mg, about 15 mg, about 20 mg, about 30 mg, about 40 mg, about 50 mg, about 60 mg, about 80 mg, about 100 mg, about 160 mg or about 320 mg of the oxycodone hydrochloride active pharmaceutical ingredient.

18. The oral dosage form of claim 6 comprising 10 mg, 15 mg, 20 mg, 30 mg, 40 mg, 60 mg, 80 mg or 160 mg of the oxycodone hydrochloride active pharmaceutical ingredient.

19. The oral dosage form of claim 3, wherein the pharmaceutically acceptable excipient comprises a sustained release carrier.