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 enhancing direct transmucosal delivery of a fentanyl or fentanyl derivative to a subject, said method comprising:
administering a bioerodible drug delivery device to an oral mucosal surface of a subject, the device comprising: a fentanyl or fentanyl derivative disposed in a mucoadhesive polymeric diffusion environment; and a barrier environment disposed relative to the polymeric diffusion environment such that a unidirectional gradient is created upon application to the mucosal surface and the fentanyl or fentanyl derivative is delivered to the subject.
2 . A method for treating pain in a subject comprising transmucosally administering to a subject a therapeutically effective amount of a fentanyl or fentanyl derivative disposed in a mucoadhesive polymeric diffusion environment such that the effective amount of the fentanyl or fentanyl derivative is delivered in less than about 30 minutes.
3 . (canceled)
4 . The method of claim 2 , wherein acute pain is alleviated in the subject.
5 . The method of claim 2 , wherein the pain is breakthrough cancer pain.
6 . A mucoadhesive delivery device suitable for direct transmucosal administration of an effective amount of a fentanyl or fentanyl derivative to a subject, the mucoadhesive device comprising: a fentanyl or fentanyl derivative disposed in a polymeric diffusion environment; and a barrier environment disposed relative to the polymeric diffusion environment such that a unidirectional gradient is upon application to a mucosal surface.
7 . The transmucosal delivery device of claim 6 , wherein the device delivers a fentanyl or fentanyl derivative with at least 50% direct buccal absorption and an absolute bioavailability of at least about 70%.
8 . A transmucosal delivery device that delivers a fentanyl or fentanyl derivative directly to the mucosa to achieve onset of pain relief (T first ) of about 0.20 hours or less and time to peak plasma concentration (T max ) of about 1.6 hours or more.
9 . A device comprising about 800 μg of fentanyl, which exhibits upon transmucosal administration to a subject at least one in vivo plasma profile selected from the group consisting of:
a C max of about 1.10 ng/mL or more;
a T first of about 0.20 hours or less; and
an AUC 0-24 of about 10.00 hr·ng/mL or more.
10 . (canceled)
11 . The device of claim 6 , wherein the pH of the mucoadhesive polymeric diffusion environment is between about 6.5 and about 8.
12 . The device of claim 6 , wherein the pH of the mucoadhesive polymeric diffusion environment is about 7.25.
13 . (canceled)
14 . The device of claim 6 , wherein the device further comprises at least one additional layer that facilitates unidirectional delivery of the fentanyl or fentanyl derivative to the mucosa.
15 - 16 . (canceled)
17 . The device of claim 6 , wherein more than 55% of the fentanyl in the device becomes systemically available.
18 - 26 . (canceled)
27 . The device of claim 6 , wherein the device comprises a pH buffering agent.
28 . The device of claim 6 , wherein the device is adapted for buccal or sublingual administration.
29 - 31 . (canceled)
32 . The device of claim 6 , wherein the device comprises a backing layer disposed adjacent to the mucoadhesive polymeric diffusion environment.
33 . The device of claim 6 , wherein the device further comprises an opioid antagonist.
34 . The device of claim 6 , wherein the device further comprises naloxone.
35 . The device of claim 6 , wherein the device is a layered, flexible device.
36 . The device of claim 6 , wherein the mucoadhesive polymeric diffusion environment has a buffered environment for the transmucosal administration.
37 . (canceled)
38 . The device of claim 6 , wherein there is about a 50% decrease in pain over about 30 minutes.
39 . The device of claim 6 , wherein the polymeric diffusion environment comprises at least one ionic polymer system.
40 . The device of claim 39 , wherein the ionic polymer system is selected from the group consisting of POLYCARBOPHIL, sodium carboxymethylcellulose and mixtures thereof.
41 . The device of claim 6 , wherein the polymeric diffusion environment comprises a buffer system.
42 . The device of claim 41 , wherein the buffer system comprises citric acid, sodium benzoate or mixtures thereof.
43 . (canceled)
44 . The device of claim 6 , wherein the device has a thickness of about 0.25 mm.
45 . (canceled)