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 providing enhanced uptake of buprenorphine to a subject by direct transmucosal delivery of buprenorphine, the method comprising:
 administering buprenorphine to a subject by application of a mucoadhesive bioerodable drug delivery device to an oral mucosal surface of the subject, the device comprising:
 a bioerodable mucoadhesive layer comprising an effective amount of buprenorphine disposed in a polymeric diffusion environment, wherein the polymeric diffusion environment is a buffered environment having a pH of between about 4 and about 6; and 
 a barrier layer comprising a polymeric barrier environment disposed adjacent to the mucoadhesive layer to provide a unidirectional gradient upon application to a mucosal surface for the rapid and efficient delivery of buprenorphine, 
   wherein the unidirectional gradient delivers buprenorphine across the buffered polymeric diffusion environment upon application to the mucosal surface,   
     
     
         2 . The method of  claim 1 , wherein the pH of the polymeric diffusion environment is between about 4.5 and about 5.5. 
     
     
         3 . The method of  claim 1 , wherein the pH of the polymeric diffusion environment is between about 4.5 and about 5. 
     
     
         4 . The method of  claim 1 , wherein a first quantifiable plasma concentration of buprenorphine is observed at about 45 minutes. 
     
     
         5 . The method of  claim 1 , wherein an effective plasma concentration of buprenorphine is maintained for at least 4 hours. 
     
     
         6 . The method of  claim 1 , wherein the device further comprises an opioid antagonist selected from the group consisting of naloxone, naltrexone, nalmefene, nalide, nalmexone, nalorphine, naluphine, cyclazocine, levallorphan and combinations thereof. 
     
     
         7 . The method of  claim 6 , wherein the opioid antagonist is naloxone. 
     
     
         8 . A mucoadhesive bioerodable drug delivery device suitable for direct transmucosal administration of buprenorphine to a subject, the mucoadhesive bioerodable drug delivery device comprising:
 a bioerodable mucoadhesive layer comprising an effective amount of buprenorphine disposed in a polymeric diffusion environment, wherein the polymeric diffusion environment is a buffered environment having a pH between about 4 and about 6; and   a barrier layer comprising a polymeric barrier environment disposed adjacent to the mucoadhesive layer to provide a unidirectional gradient upon application to a mucosal surface for the rapid and efficient delivery of buprenorphine,   wherein the unidirectional gradient delivers buprenorphine across the buffered polymeric diffusion environment.   
     
     
         9 . The device of  claim 8 , wherein the pH of the polymeric diffusion environment is between about 4.5 and about 5.5. 
     
     
         10 . The device of  claim 8 , wherein the pH of the polymeric diffusion environment is between about 4.5 and about 5. 
     
     
         11 . The device of  claim 8 , wherein the device further comprises an opioid antagonist selected from the group consisting of naloxone, naltrexone, nalmefene, nalide, nalmexone, nalorphine, naluphine, cyclazocine, levallorphan and combinations thereof. 
     
     
         12 . The device of  claim 11 , wherein the opioid antagonist is naloxone.