Abuse-resistant mucoadhesive devices for delivery of buprenorphine

Abstract

The present invention provides abuse deterrent mucoadhesive devices for delivery of buprenorphine. Each device comprises a mucoadhesive layer and a backing layer, and the pH in each layer is selected, such that absorption of buprenorphine is maximized.

1 . A mucoadhesive device for use in managing opioid dependence, the device comprising:
 a mucoadhesive layer comprising between about 0.075 mg to about 12 mg of buprenorphine having a pH in a range between about 4 to about 6; and   a backing layer comprising between about 0.0125 mg to about 2 mg of naloxone having a pH lower than said mucoadhesive layer and in a range of up to about half a pH unit below said pH range of said mucoadhesive layer.   
     
     
         2 . The mucoadhesive device of  claim 1 , wherein the mucoadhesive layer and the backing layer comprise different combinations of polymers. 
     
     
         3 . The mucoadhesive device of  claim 1  wherein the mucoadhesive layer is buffered to a pH of between about 4 to about 6 and the a backing is buffered to a pH lower than said mucoadhesive layer and in a range of up to about half a pH unit below said pH range of said mucoadhesive layer. 
     
     
         4 . The mucoadhesive device for use in managing opioid dependence of  claim 1 , wherein the mucoadhesive layer comprises between about 1 mg to about 1.5 mg of buprenorphine having a pH in a range between about 4 and about 6; and
 the backing layer comprising between about 0.145 mg to about 0.2 mg of naloxone having a pH lower than said mucoadhesive layer and in a range of up to about half a pH unit below said pH range of said mucoadhesive layer.   
     
     
         5 . The mucoadhesive device for use in managing opioid dependence of  claim 4 , wherein the mucoadhesive layer and the backing layer comprise different combinations of polymers. 
     
     
         6 . The mucoadhesive device of  claim 4 , wherein the mucoadhesive layer is buffered to a pH of between about 4 to about 6 and the a backing is buffered to a pH lower than said mucoadhesive layer and in a range of up to about half a pH unit below said pH range of said mucoadhesive layer. 
     
     
         7 . The mucoadhesive device for use in managing opioid dependence of  claim 1 , wherein the mucoadhesive layer comprises between about 2 mg to about 2.5 mg of buprenorphine having a pH in a range between about 4 and about 6; and
 the backing layer comprising between about 0.3 mg to about 0.4 mg of naloxone having a pH lower than said mucoadhesive layer and in a range of up to about half a pH unit below said pH range of said mucoadhesive layer.   
     
     
         8 . The mucoadhesive device for use in managing opioid dependence of  claim 7 , wherein the mucoadhesive layer and the backing layer comprise different combinations of polymers. 
     
     
         9 . The mucoadhesive device of  claim 7 , wherein the mucoadhesive layer is buffered to a pH of between about 4 to about 6 and the a backing is buffered to a pH lower than said mucoadhesive layer and in a range of up to about half a pH unit below said pH range of said mucoadhesive layer. 
     
     
         10 . A mucoadhesive device for use in managing opioid dependence, the device comprising:
 a mucoadhesive layer comprises between about 4 mg to about 4.5 mg of buprenorphine having a pH in a range between about 4 and about 6; and   a backing layer comprising between about 0.6 mg to about 0.7 mg of naloxone having a pH lower than said mucoadhesive layer and in a range of up to about half a pH unit below said pH range of said mucoadhesive layer.   
     
     
         11 . The mucoadhesive device of  claim 10 , wherein the mucoadhesive layer and the backing layer comprise different combinations of polymers. 
     
     
         12 . The mucoadhesive device of  claim 10 , wherein the mucoadhesive layer is buffered to a pH of between about 4 to about 6 and the backing layer is buffered to a pH lower than said mucoadhesive layer and in a range of up to about half a pH unit below said pH range of said mucoadhesive layer. 
     
     
         13 . A mucoadhesive device for use in managing opioid dependence, the device comprising:
 a mucoadhesive layer comprises between about 6 mg to about 6.5 mg of buprenorphine having a pH in a range between about 4 and about 6; and   a backing layer comprising between about 1 mg to about 1.1 mg of naloxone having a pH lower than said mucoadhesive layer and in a range of up to about half a pH unit below said pH range of said mucoadhesive layer.   
     
     
         14 . The mucoadhesive device of  claim 13 , wherein the mucoadhesive layer and the backing layer comprise different combinations of polymers. 
     
     
         15 . The mucoadhesive device of  claim 13 , wherein the mucoadhesive layer is buffered to a pH of between about 4 to about 6 and the a backing layer is buffered to a pH lower than said mucoadhesive layer and in a range of up to about half a pH unit below said pH range of said mucoadhesive layer. 
     
     
         16 . A method of managing opioid dependence by administering to a subject in need thereof a device for direct transmucosal delivery of buprenorphine to a buccal surface, the device comprising:
 a mucoadhesive layer comprising between about 0.075 mg to about 12 mg of buprenorphine having a pH in a range of between about 4 and about 6; and   a backing layer comprising between about 0.0125 mg to about 2 mg of naloxone having a pH lower than said mucoadhesive layer and in a range of up to about half a pH unit below said pH range of said mucoadhesive layer.   
     
     
         17 . The method of  claim 16 , wherein the mucoadhesive layer and the backing layer of said device comprise different combinations of polymers. 
     
     
         18 . The mucoadhesive device of  claim 16 , wherein the mucoadhesive layer is buffered to a pH of between about 4 to about 6 and the a backing is buffered to a pH lower than said mucoadhesive layer and in a range of up to about half a pH unit below said pH range of said mucoadhesive layer. 
     
     
         19 . The mucoadhesive device of  claim 1 , wherein the w/w ratio of buprenorphine to naloxone present in the device is 6:1.