Pharmaceutical formulation containing bittering agent

• US 7,141,250 B2
• Filed: 08/06/2002
• Issued: 11/28/2006
• Est. Priority Date: 08/06/2001
• Status: Expired due to Term

• Current Assignee: Purdue Pharma L.P.
• Original Assignee: Euroceltique SA
• Inventors: Wright, Curtis, Oshlack, Benjamin, Breder, Christopher, Colucci, Robert
• Primary Examiner(s): TRAN, SUSAN T
• Application Number:
  US10/213,920
• Publication Number:
  US 20030064099A1
• Time in Patent Office: 1,575 Days
• Field of Search: 424/451, 424/452, 424/464, 424/465, 424/468, 424/484, 424/489
• US Class Current: 424/490
• CPC Class Codes: A61K 9/2013 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/205 Polysaccharides, e.g. alginate, gums; Cyclodextrin
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose

Abstract

Disclosed in certain embodiments is an oral dosage form comprising a therapeutically effective amount of a drug susceptible to abuse; and an effective amount of a bittering agent to impart a bitter taste to an abuser upon administration of said dosage form after tampering.

Claims

1. An oral dosage form comprising:

a therapeutically effective amount of an opioid analgesic; and

a sequestered bittering agent, which bittering agent is substantially released only upon tampering of the dosage form in an amount sufficient to impart a bitter taste to an abuser upon oral administration of said tampered dosage form wherein said sequestered bittering agent is present in multiparticulates individually coated with a material that prevents release of the bittering agent.

2. The oral dosage form of claim 1, wherein the bittering agent is selected from the group consisting of flavor oils;

flavoring aromatics;

oleoresins;

extracts derived from plants;

sucrose derivatives;

chlorosucrose derivatives;

quinine sulphate;

denatonium benzoate; and

combinations thereof.

3. The oral dosage form of claim 1, wherein the bittering agent is a flavor oil selected from the group consisting of spearmint oil, peppermint oil, eucalyptus oil, oil of nutmeg, allspice, mace, oil of bitter almonds, menthol and combinations thereof.

4. The oral dosage form of claim 1, wherein the bittering agent is a fruit flavor selected from the group consisting of lemon, orange, lime, grapefruit, and mixtures thereof.

5. The oral dosage form of claim 1, wherein the bittering agent is denatonium benzoate.

6. The oral dosage form of claim 1, wherein said opioid analgesic is morphine, codeine, tramadol or a pharmaceutically acceptable salt thereof.

7. The oral dosage form of claim 1, wherein said opioid analgesic is hydromorphone or a pharmaceutically acceptable salt thereof.

8. The oral dosage form of claim 1, wherein said opioid analgesic is hydrocodone or a pharmaceutically acceptable salt thereof.

9. The oral dosage form of claim 1, wherein said opioid analgesic is oxycodone or a pharmaceutically acceptable salt thereof.

10. The oral dosage form of claim 1, wherein said bittering agent is in an amount of less than about 50% by weight of the dosage form.

11. The oral dosage form of claim 1, wherein said bittering agent is in an amount of less than about 10% by weight of the dosage form.

12. The oral dosage form of claim 1, wherein said bittering agent is in an amount of less than about 5% by weight of the dosage form.

13. The oral dosage form of claim 1, wherein said bittering agent is in an amount of from about 0.1 to 1.0 percent by weight of the dosage form.

14. The oral dosage form of claim 1, further comprising a pharmaceutically acceptable excipient.

15. The oral dosage forms of claim 14 wherein said excipient is a sustained release excipient.

16. The oral dosage form of claim 1, said dosage form providing an analgesic effect for at least about 12 hours after oral administration to a human patient.

17. The oral dosage form of claim 1 wherein said bittering agent is at least partially interdispersed with the opioid analgesic.

18. A method of treating pain comprising administering to a patient an oral dosage form of claim 1.

19. A method of preparing a pharmaceutical dosage form comprising combining a therapeutically effective amount of an opioid analgesic with a bittering agent into an oral dosage form, which bittering agent is substantially released from the oral dosage form only upon tampering of the dosage form in an amount sufficient to impart a bitter taste to a subject upon oral administration of said tampered dosage form wherein said sequestered bittering agent is present in multiparticulates individually coated with a material that substantially prevents release of the bittering agent.

20. A method of preparing a pharmaceutical dosage form comprising combining a therapeutically effective amount of an opioid analgesic with a sequestered bittering agent into an oral dosage form, which bittering agent is substantially released from the oral dosage form only upon tampering of the dosage form in an amount sufficient to impart a bitter taste to a subject upon oral administration of said tampered dosage form, wherein said sequestered bittering agent is dispersed in a matrix comprising a sequestering material that substantially prevents the release of said bittering agent.

21. An oral dosage form comprising:

a therapeutically effective amount of an opioid analgesic; and

sequestered bittering agent, which bittering agent is substantially released only upon tampering of the dosage form in an amount sufficient to impart a bitter taste to an abuser upon oral administration of said tampered dosage form, wherein said sequestered bittering agent is dispersed in a matrix comprising a sequestering material that substantially prevents the release of said bittering agent.

22. The oral dosage form of claim 21, wherein the bittering agent is selected from the group consisting of flavor oils;

flavoring aromatics;

oleoresins;

extracts derived from plants, leaves, flowers;

fruit flavors;

sucrose derivatives;

chlorosucrose derivatives;

quinine sulphate;

denatonium benzoate; and

combinations thereof.

23. The oral dosage form of claim 21, wherein the bittering agent is a flavor oil selected from the group consisting of spearmint oil, peppermint oil, eucalyptus oil, oil of nutmeg, allspice, mace, oil of bitter almonds, menthol and combinations thereof.

24. The oral dosage form of claim 21, wherein the bittering agent is a fruit flavor selected from the group consisting of lemon, orange, lime, grapefruit, and mixtures thereof.

25. The oral dosage form of claim 21, wherein the bittering agent is denatonium benzoate.

26. The oral dosage form of claim 21, wherein said opioid analgesic is morphine, codeine, tramadol or pharmaceutically acceptable salt thereof.

27. The oral dosage form of claim 21, wherein said opioid analgesic is hydromorphone or a pharmaceutically acceptable salt thereof.

28. The oral dosage form of claim 21, wherein said opioid analgesic is hydrocodone or a pharmaceutically acceptable salt thereof.

29. The oral dosage form of claim 21, wherein said opioid analgesic is oxycodone or a pharmaceutically acceptable salt thereof.

30. The oral dosage form of claim 21, wherein said bittering agent is in an amount of less than about 50% by weight of the dosage form.

31. The oral dosage form of claim 21, wherein said bittering agent is in an amount of less than about 10% by weight of the dosage form.

32. The oral dosage form of claim 21, wherein said bittering agent is in an amount of less than about 5% by weight of the dosage form.

33. The oral dosage form of claim 21, wherein said bittering agent is in an amount of from about 0.1 to 1.0% by weight of the dosage form.

34. The oral dosage forms of claim 21, further comprising a pharmaceutically acceptable excipient.

35. The oral dosage form of claim 34, wherein said excipient is a sustained release excipient.

36. The oral dosage form of claim 21, wherein said dosage form provides an analgesic effect for at least about 12 hours after oral administration to a human patient.

37. The oral dosage form of claim 21, wherein said irritant is at least partially interdispersed with the opioid analgesic.

38. A method of treating pain comprising administering to a patient an oral dosage form of claim 21.