Pharmaceutical formulation containing opioid agonist, opioid antagonist and bittering agent

• US 20030124185A1
• Filed: 08/06/2002
• Published: 07/03/2003
• Est. Priority Date: 08/06/2001
• Status: Active Grant

• Current Assignee: Purdue Pharma L.P.
• Original Assignee: Purdue Pharma L.P.
• Inventors: Wright, Curtis, Oshlack, Benjamin, Breder, Christopher, Colucci, Robert
• Granted Patent: US 7,144,587 B2
• Time in Patent Office: Days
• US Class Current: 424/465
• CPC Class Codes: A61K 9/1635 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/1647 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61K 9/2013 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/2018 Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
• CPC Class Codes: A61K 9/2027 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/205 Polysaccharides, e.g. alginate, gums; Cyclodextrin
• CPC Class Codes: A61K 9/2081 with microcapsules or coated microparticles according to A61K9/50
• CPC Class Codes: A61K 9/5078 with drug-free core

Abstract

Disclosed in certain embodiments is an oral dosage form comprising a therapeutically effective amount of an opioid analgesic; an opioid antagonist; and a bittering agent in an effective amount to impart a bitter taste to an abuser upon administration of the dosage form after tampering.

Claims

1. A oral dosage form comprising:

a therapeutically effective amount of an opioid analgesic;

an opioid antagonist; and

a bittering agent in an effective amount to impart a bitter taste to an abuser upon administration of said dosage form after tampering.

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, leaves, flowers, fruit flavors;

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.

7. The oral dosage form of claim 1, wherein the antagonist is in a sequestered form.

8. The oral dosage form of claim 1, wherein the antagonist and the bittering agent are both in sequestered forms.

9. 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.

10. 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.

11. 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

12. 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.

13. The oral dosage forms of claim 1, further comprising a pharmaceutically acceptable excipient.

14. The oral dosage forms of claim 13, wherein said excipient is a sustained release excipient.

15. The oral dosage form of claim 13, said dosage form providing an analgesic effect for at least about 12 hours after oral administration to a human patient.

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

17. The dosage form of claim 1 having a ratio of opioid antagonist to opioid agonist that is analgesically effective when the combination is administered orally, but which is aversive in physically dependent human subjects when administered at the same amount or at a higher amount than said therapeutically effective amount.

18. The dosage form of claim 17 wherein said ratio of opioid antagonist to opioid agonist maintains an analgesic effect but does not increase analgesic efficacy of the opioid agonist relative to the same therapeutic amount of opioid analgesic when administered to human patients without said opioid antagonist.

19. The oral dosage form of claim 1, wherein the antagonist is in an amount to attenuate a side effect of said opioid agonist selected from the group consisting of anti-analgesia, hyperalgesia, hyperexcitability, physical dependence, tolerance, and a combination of any of the foregoing.

20. The oral dosage form of claim 1, wherein the amount of antagonist released during the dosing interval enhances the analgesic potency of the opioid agonist.

21. The oral dosage form of claim 1, wherein the amount of the releasable opioid receptor antagonist is about 100 to about 1000 fold less than the amount of the opioid agonist.

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

6. The oral dosage form of clam 1, wherein the bittering agent is in a sequestered form.

23. A method of preparing a pharmaceutical dosage form comprising ombining a therapeutically effective amount of an opioid analgesic;

and an antagonist in a dosage form with an effective amount of a bittering agent to impart a bitter taste to an abuser upon administration of said dosage form after tampering.

24. The method of claim 23, wherein said bittering agent is at least partially interdispersed with the opioid analgesic.

25. A method of preventing abuse of an oral dosage form of an opioid analgesic comprising:

preparing the dosage form with an analgesically effective amount of an opioid analgesic;

an antagonist; and

a bittering agent in an effective amount to impart a bitter taste to an abuser upon administration of said dosage form after tampering.