Transmucosal delivery devices with enhanced uptake
The present invention provides methods for enhancing transmucosal uptake of a medicament, e.g., fentanyl or buprenorphine, to a subject and related devices. The method includes administering to a subject a transmucosal drug delivery device comprising the medicament. Also provided are devices suitable for transmucosal administration of a medicament to a subject and methods of their administration and use. The devices include a medicament disposed in a mucoadhesive polymeric diffusion environment and a barrier environment.
1. A method for delivering fentanyl to a human comprising:
administering a mucoadhesive biodegradable drug delivery device for transmucosal delivery to the oral mucosa of said human, the device comprising:
a biodegradable mucoadhesive layer comprising fentanyl disposed in a polymeric diffusion environment, wherein the polymeric diffusion environment has a pH of between about 6 and about 8.5; and
a polymeric barrier environment disposed adjacent to the mucoadhesive layer, wherein a unidirectional diffusion gradient of fentanyl is provided upon application to a buccal surface,
wherein the overall bioavailability of fentanyl is at least about 60%; and
wherein the fentanyl is delivered in less than about 30 minutes.
2. The method of claim 1 , wherein the overall bioavailability of fentanyl is at least about 70%.
3. The method of claim 1 , wherein the polymeric diffusion environment comprises at least one film-forming water-erodible adhesive polymer and at least one bioadhesive polymer.
4. The method of claim 1 , wherein said polymeric barrier environment comprises at least one film-forming water-erodible polymer.
5. The method of claim 1 , wherein the polymeric diffusion environment has a pH of between about 7 to about 7.5.
6. The method of claim 1 , wherein the mucoadhesive biodegradable drug delivery device further comprises an opioid antagonist.
7. The method of claim 1 , wherein the biodegradable drug delivery device further comprises a third layer or coating.
8. The method of claim 1 , wherein the polymeric diffusion environment has a pH buffered to between about 6 and about 8.5.
9. The method of claim 1 , wherein the polymeric diffusion environment has a pH buffered to between about 7 to about 7.5.
10. The method of claim 8 , wherein the overall bioavailability of fentanyl is at least about 70%.
11. The method of claim 8 , wherein the polymeric diffusion environment comprises at least one film-forming water-erodible adhesive polymer and at least one bioadhesive polymer.
12. The method of claim 8 , wherein said polymeric barrier environment comprises at least one film-forming water-erodible polymer.
13. The method of claim 8 , wherein the mucoadhesive biodegradable drug delivery device further comprises an opioid antagonist.
14. The method of claim 8 , wherein the biodegradable drug delivery device further comprises a third layer or coating.
15. A device for delivering fentanyl to a human, the device comprising:
a biodegradable mucoadhesive layer comprising fentanyl disposed in a polymeric diffusion environment, wherein the polymeric diffusion environment has a pH of between about 6 and about 8.5; and
a polymeric barrier environment disposed adjacent to the mucoadhesive layer, wherein a unidirectional diffusion gradient of fentanyl is provided upon application to a buccal surface of a subject,
wherein upon application to a buccal surface, the overall bioavailability of fentanyl is at least about 60%; and
wherein the fentanyl is delivered in less than about 30 minutes.
16. The device of claim 15 , wherein the overall bioavailability of fentanyl is at least about 70%.
17. The device of claim 15 , wherein the polymeric diffusion environment comprises at least one film-forming water-erodible adhesive polymer and at least one bioadhesive polymer.
18. The device of claim 15 , wherein said polymeric barrier environment comprises at least one film-forming water-erodible polymer.
19. The device of claim 15 , wherein the polymeric diffusion environment has a pH of between about 7 to about 7.5.
20. The device of claim 15 , wherein the mucoadhesive biodegradable drug delivery device further comprises an opioid antagonist.
21. The device of claim 15 , wherein the biodegradable drug delivery device further comprises a third layer or coating.
22. The device of claim 15 , wherein the polymeric diffusion environment has a pH buffered to between about 6 and about 8.5.
23. The device of claim 15 , wherein the polymeric diffusion environment has a pH buffered to between about 7 to about 7.5.
24. The device of claim 22 , wherein the overall bioavailability of fentanyl is at least about 70%.
25. The device of claim 22 , wherein the polymeric diffusion environment comprises at least one film-forming water-erodible adhesive polymer and at least one bioadhesive polymer.
26. The device of claim 22 , wherein said polymeric barrier environment comprises at least one film-forming water-erodible polymer.
27. The device of claim 22 , wherein the mucoadhesive biodegradable drug delivery device further comprises an opioid antagonist.
28. The device of claim 27 , wherein said opioid antagonist is naloxone.
29. The device of claim 22 , wherein the biodegradable drug delivery device further comprises a third layer or coating.
30. A method for treating pain, the method comprising:
adhering a mucoadhesive biodegradable drug delivery device to a buccal surface of a human, the device comprising:
a biodegradable mucoadhesive layer comprising a therapeutically effective amount of fentanyl for treating pain disposed in a polymeric diffusion environment, wherein the polymeric diffusion environment has a pH buffered to between about 6 and about 8.5; and
a polymeric barrier environment disposed adjacent to the mucoadhesive layer wherein a unidirectional diffusion gradient of fentanyl is provided upon application to the buccal surface,
wherein the transmucosal delivery of fentanyl is at least about 50% by direct buccal absorption,
wherein the overall bioavailability of fentanyl is at least about 70%; and
wherein the fentanyl is delivered in less than about 30 minutes.