Transdermal Delivery Systems

Abstract

Disclosed are bupivacaine transdermal delivery systems, and related methods.

1 . A transdermal delivery system, comprising:
 a backing layer; and   a pressure sensitive adhesive composition, comprising:
 bupivacaine; and 
 sucrose acetate isobutyrate present in an amount effective to reduce a peel force of the transdermal delivery system compared to a peel force of a transdermal delivery system comprising an otherwise identical pressure sensitive adhesive composition that does not comprise sucrose acetate isobutyrate. 
   
     
     
         2 .- 8 . (canceled) 
     
     
         9 . A transdermal delivery system comprising:
 a backing layer, and   a reservoir laminated to the backing layer that comprises bupivacaine in an amount ranging from about 0.1 to about 0.5 mg/cm 2 ; and   wherein the reservoir is adapted to transdermally deliver the bupivacaine from the transdermal delivery system to a subject for a period such that the following mean plasma concentrations are achieved:   a mean plasma concentration, normalized to an initial loading of the transdermal delivery system, ranging from about 0.0003 to about 0.7 cm 2 /L at about 12 hours after initiation of the transdermal delivery; and   a mean plasma concentration, normalized to an initial loading of the transdermal delivery system, ranging from about 0.0014 to about 0.4 cm 2 /L at about 24 hours after initiation of the transdermal delivery.   
     
     
         10 . The transdermal delivery system of  claim 9 , wherein the reservoir is further adapted to transdermally deliver the bupivacaine from the transdermal delivery system to a subject for a three day period such that the following mean plasma concentrations are achieved: a mean plasma concentration, normalized to an initial loading of the transdermal delivery system, ranging from about 0.0013 to 0.3 cm 2 /L at about 48 hours after initiation of the transdermal delivery. 
     
     
         11 . The transdermal delivery system of  claim 9 , wherein the reservoir is further adapted to transdermally deliver the bupivacaine from the transdermal delivery system to a subject for a three day period such that the following mean plasma concentrations are achieved: a mean plasma concentration, normalized to an initial loading of the transdermal delivery system, ranging from about 0.001 to 0.31 cm 2 /L at about 72 hours after initiation of the transdermal delivery. 
     
     
         12 . The transdermal delivery system of  claim 9 , wherein the reservoir is further adapted to transdermally deliver the bupivacaine from the transdermal delivery system to a subject for a period such that the following mean plasma concentrations are achieved:
 a mean plasma concentration, normalized to an initial loading of the transdermal delivery system, ranging from about 0.003 to about 0.07 cm 2 /L at about 12 hours after initiation of the transdermal delivery; and   a mean plasma concentration, normalized to an initial loading of the transdermal delivery system, ranging from about 0.014 to about 0.04 cm 2 /L at about 24 hours after initiation of the transdermal delivery.   
     
     
         13 . The transdermal delivery system of  claim 12 , wherein the reservoir is further adapted to transdermally deliver the bupivacaine from the transdermal delivery system to a subject for the period such that the following mean plasma concentrations are achieved: a mean plasma concentration, normalized to an initial loading of the transdermal delivery system, ranging from about 0.013 to 0.03 cm 2 /L at about 48 hours after initiation of the transdermal delivery. 
     
     
         14 . The transdermal delivery system of  claim 12 , wherein the reservoir is further adapted to transdermally deliver the bupivacaine from the transdermal delivery system to a subject for the period such that the following mean plasma concentrations are achieved: a mean plasma concentration, normalized to an initial loading of the transdermal delivery system, ranging from about 0.01 to 0.031 cm 2 /L at about 72 hours after initiation of the transdermal delivery. 
     
     
         15 . The transdermal delivery system of  claim 9 , wherein the period is about two days. 
     
     
         16 . The transdermal delivery system of  claim 15 , wherein the reservoir is further adapted to provide a residual amount of bupivacaine in the transdermal delivery system following the two day period of use ranging from about 20 wt % to about 85 wt %, based on the total weight of bupivacaine in the transdermal delivery system prior to transdermal delivery. 
     
     
         17 . The transdermal delivery system of  claim 16 , wherein the reservoir is further adapted to provide a residual amount of bupivacaine in the transdermal delivery system following the two day period of use ranging from about 30 wt % to about 75 wt % based on the total weight of bupivacaine in the transdermal delivery system prior to transdermal delivery. 
     
     
         18 . The transdermal delivery system of  claim 17 , wherein the reservoir is further adapted to provide a residual amount of bupivacaine in the transdermal delivery system following the two day period of use ranging from about 40 wt % to about 60 wt % based on the total weight of bupivacaine in the transdermal delivery system prior to transdermal delivery. 
     
     
         19 . The transdermal delivery system of  claim 9 , wherein the period is about 3 days. 
     
     
         20 . The transdermal delivery system of  claim 19 , wherein the reservoir is further adapted to provide a residual amount of bupivacaine in the transdermal delivery system following the three day period of use ranging from about 20 wt % to about 85 wt %, based on the total weight of bupivacaine in the transdermal delivery system prior to transdermal delivery. 
     
     
         21 . The transdermal delivery system of  claim 20 , wherein the reservoir is further adapted to provide a residual amount of bupivacaine in the transdermal delivery system following the three day period of use ranging from about 30 wt % to about 75 wt % based on the total weight of bupivacaine in the transdermal delivery system prior to transdermal delivery. 
     
     
         22 . (canceled) 
     
     
         23 . A method comprising:
 applying to a subject the transdermal delivery system of  claim 9 ; and   transdermally delivering the bupivacaine from the transdermal delivery system to the subject.   
     
     
         24 .- 25 . (canceled) 
     
     
         26 . The transdermal delivery system of  claim 9 , wherein the reservoir comprises pressure sensitive adhesive material, and wherein the reservoir has a solubility for the bupivacaine ranging from about 1 wt % to about 25 wt % of total weight of the pressure sensitive adhesive material. 
     
     
         27 . The method of  claim 23 , wherein the reservoir comprises pressure sensitive adhesive material, and wherein the reservoir has a solubility for the bupivacaine ranging from about 1 wt % to about 25 wt % of total weight of the pressure sensitive adhesive material. 
     
     
         28 . The transdermal delivery system of  claim 9 , wherein the reservoir comprises at least one member selected from polyacrylate, polysiloxane, polyisobutylene, polyisoprene, polybutadiene, and styrenic block polymer. 
     
     
         29 . The transdermal delivery system of  claim 26 , wherein the reservoir comprises at least one member selected from polyacrylate, polysiloxane, polyisobutylene, polyisoprene, polybutadiene, and styrenic block polymer. 
     
     
         30 . The method of  claim 23 , wherein the reservoir comprises at least one member selected from polyacrylate, polysiloxane, polyisobutylene, polyisoprene, polybutadiene, and styrenic block polymer.