Abuse resistant transmucosal drug delivery device

• US 20070148097A1
• Filed: 12/13/2006
• Published: 06/28/2007
• Est. Priority Date: 12/13/2005
• Status: Active Grant

• Current Assignee: Biodelivery Sciences International Incorporated
• Original Assignee: Biodelivery Sciences International Incorporated
• Inventors: Finn, Andrew, Vasisht, Niraj
• Granted Patent: US 9,522,188 B2
• Time in Patent Office: Days
• US Class Current: 424/10.200
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/4468 having a nitrogen directly attached in position 4, e.g. clebopride, fentanyl
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0014 Skin, i.e. galenical aspects of topical compositions non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00
• CPC Class Codes: A61K 9/006 Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
• CPC Class Codes: A61K 9/7007 Drug-containing films, membranes or sheets A61K9/0041, A61K9/0043, A61K9/006, A61K9/0063 take precedence
• CPC Class Codes: A61K 9/7038 Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer
• CPC Class Codes: A61K 9/7092 Transdermal patches having multiple drug layers or reservoirs, e.g. for obtaining a specific release pattern, or for combining different drugs
• CPC Class Codes: A61P 25/30 for treating abuse or dependence

Abstract

The present invention relates to a solid pharmaceutical dosage form for abusable drug delivery with reduced illicit abuse potential. The dosage form is presented as a bioerodable transmucosal delivery device that includes an abusable drug and an antagonist to the abusable drug associated with an abuse-resistant matrix. The devices of the invention may be in the form of a layered film or a tablet. Upon application in a non-abusive manner, the device adheres to the mucosal surface, providing transmucosal drug delivery of the drug with minimal absorption of the antagonist into systemic circulation.

Claims

1. A bioerodable abuse-resistant drug delivery device comprising:

a transmucosal delivery composition comprising an abusable drug; and

an abuse-resistant matrix comprising an antagonist to the abusable drug.

2. The delivery device of claim 1, wherein the antagonist is substantially transmucosally unavailable.

4. The delivery device of claim 1, wherein the device is a mucoadhesive drug delivery device.

12. The delivery device of claim 1, comprising a mucoadhesive layer.

13. The delivery device of claim 12, wherein either or both of the abusable drug and the abuse-resistant matrix are incorporated into the mucoadhesive layer.

14. The drug delivery device of claim 1, comprising a mucoadhesive layer and a non-adhesive backing layer.

15. The delivery device of claim 14, wherein the abusable drug is incorporated into a third layer disposed between the mucoadhesive layer and the backing layer.

16. The delivery device of claim 14, wherein the abuse-resistant matrix is incorporated into in a third layer disposed between the mucoadhesive layer and the backing layer.

17. The delivery device of claim 14, wherein the abuse-resistant matrix is a third layer disposed between the mucoadhesive layer and the backing layer.

18. The delivery device of claim 14, wherein the abuse-resistant matrix is incorporated into the mucoadhesive layer and/or the backing layer.

19. The delivery device of claim 14, wherein the abusable drug is incorporated into the mucoadhesive layer and the abuse-resistant matrix is incorporated into the backing layer.

20. The delivery device of claim 15, wherein the abuse-resistant matrix erodes at a slower rate than the backing layer, the mucoadhesive layer, the third layer, or any combination thereof.

21. The delivery device according to claim 1, wherein the abusable drug is selected from the group consisting of opiates and opioids.

22. The delivery device according to claim 1 any of the foregoing, wherein the device comprises at least one abusable drug selected from the group consisting of:

alfentanil, allylprodine, alphaprodine, apomorphine, anileridine, apocodeine, benzylmorphine, bezitramide, buprenorphine, butorphanol, clonitazene, codeine, cyclorphan, cyprenorphine, desomorphine, dextromoramide, dextropropoxyphene, dezocine, diampromide, diamorphone, dihydrocodeine, dihydromorphine, dimenoxadol, eptazocine, ethylmorphine, etonitazene, etorphine, fentanyl, fencamfamine, fenethylline, hydrocodone, hydromorphone, hydroxymethylmorphinan, hydroxypethidine, isomethadone, levomethadone, levophenacylmorphan, levorphanol, lofentanil, mazindol, meperidine, metazocine, methadone, methylmorphine, modafinil, morphine, nalbuphene, necomorphine, normethadone, normorphine, opium, oxycodone, oxymorphone, pholcodine, profadol remifentanil, sufentanil, tramadol, corresponding derivatives, physiologically acceptable compounds, salts and bases.

23. The delivery device according to claim 1, wherein the antagonist comprises at least one opiate or opioid antagonist selected from the group consisting of naloxone, naltrexone, nalmefene, nalide, nalmexone, nalorphine, naluphine, cyclazocine, levallorphan and physiologically acceptable salts and solvates thereof.

27. The abuse-resistant drug delivery device of claim 1, wherein the antagonist and the abusable drug are released at substantially the same rate when abusively dissolved.

28. The abuse-resistant drug delivery device of claim 1, wherein the antagonist and the abusable drug are released at substantially the same rate when dissolved in water.

29. The abuse-resistant drug delivery device of claim 27, wherein the ratio of released antagonist to released abusable drug is not less than about 1:

20.

30. A method for treating pain in a subject comprising administering a device according to claim 1 such that pain is treated.

31. The method of claim 30, wherein the extent of the absorption into systemic circulation of the antagonist by the subject is less than about 15% by weight.

32. The method of claim 30, wherein the dosage of the abusable drug is between about 50 μ

g and about 10 mg.

3. (canceled)

5-11. -11. (canceled)

24-26. -26. (canceled)

33. A bioerodable abuse-resistant drug delivery device comprising:

a layered film having

at least one bioerodable, mucoadhesive layer to be placed in contact with a mucosal surface, and

at least one bioerodable nonadhesive backing layer,

wherein at least one abusable drug is incorporated in at least the mucoadhesive layer, and an abuse-resistant matrix comprising an antagonist to the abusable drug is incorporated in any or all of the layers.