Fentanyl suspension-based silicone adhesive formulations and devices for transdermal delivery of fentanyl

Abstract

Silicone adhesive formulations are provided, in which fentanyl particles are suspended one or more a solvated silicone adhesives. The formulations can be used for manufacturing improved, matrix-type transdermal devices for administering fentanyl.

1 - 18 . (canceled) 
     
     
         19 . A method for making a monolithic suspension-blend transdermal patch comprising:
 (a) contacting at least a portion of an inner surface of a backing layer having inner and outer surfaces and being substantially impervious to fentanyl with a first surface of a first adhesive layer, the adhesive layer comprising a uniform suspension of a therapeutically-effective amount of fentanyl particles suspended in a silicone adhesive, the fentanyl particles consisting essentially of non-recrystallized fentanyl; and   (b) contacting a removable release liner with a second surface of the adhesive layer; wherein the silicone adhesive comprises a heptane solvent fully-solvated silicone adhesive from which the heptane solvent is substantially removed.   
     
     
         20 . The method of  claim 19 , wherein the adhesive comprises a pressure sensitive adhesive. 
     
     
         21 . The method of  claim 19 , wherein the adhesive layer comprises about 1% to about 15% w/w fentanyl. 
     
     
         22 . The method of  claim 19 , wherein the adhesive layer further comprises up to 25% w/w silicone fluid. 
     
     
         23 . The method of  claim 22 , wherein the silicone fluid comprises polydimethylsiloxane. 
     
     
         24 . The method of  claim 19 , further comprising contacting a second adhesive layer with the backing layer and the first adhesive layer; the second adhesive layer extending at least partially beyond the first adhesive layer. 
     
     
         25 . The method of  claim 19 , wherein the adhesive layer further comprises a flux enhancer. 
     
     
         26 . A method for making a monolithic suspension-blend transdermal patch comprising:
 (a) contacting an inner layer of a backing layer having inner and outer surfaces and being substantially impervious to fentanyl with first surface of a first adhesive layer, the adhesive layer comprising a uniform suspension of a 72 to 168 hour period therapeutically-effective amount of fentanyl particles suspended in a silicone adhesive, the fentanyl particles consisting essentially of non-recrystallized fentanyl, the silicone adhesive comprising heptane solvent fully-solvated silicone adhesive from which the heptane solvent is substantially removed, the heptane solvated adhesive being incapable of dissolving greater than 1% w/w of said fentanyl particles; and   (b) contacting a second surface of the adhesive layer with a removable release liner; wherein the fentanyl load of the suspension-based patch ranges from about 1 to about 15% w/w (dry weight) based upon the weight of the fentanyl silicone adhesive suspension; whereby when the suspension-blend patch is administered to a subject in need thereof, the adhesive layer delivers from about 5 μg/hr to about 250 μg/hr of the fentanyl to the subject for the period.