Transmucosal delivery devices with enhanced uptake

Abstract

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)