Transdermal delivery systems

Abstract

Disclosed are bupivacaine transdermal delivery systems, and related methods.

1 . A pressure sensitive adhesive composition, capable of being incorporated into a transdermal delivery system, comprising:
 one or more rheology and surface energy modifying agents present in an amount effective to reduce a peel force of the transdermal delivery system by at least 10% compared to the peel force of the transdermal delivery system comprising a pressure sensitive adhesive composition that does not comprise the one or more rheology and surface energy modifying agents.   
     
     
         2 . The pressure sensitive adhesive composition of  claim 1 , wherein the one or more rheology and surface energy modifying agents comprises sucrose acetate isobutyrate, 1,6-hexanediol lactate glycolate, 1,6-hexanediol lactate caproate, glycerol lactate caproate, glycerol lactate glycolate, glycerol lactate glycolate with succinic anhydride, glycolic acid lactate glycolate, or lactic acid lactate glycolate. 
     
     
         3 . The pressure sensitive adhesive composition of  claim 1 , wherein the one or more rheology and surface energy modifying agents comprises sucrose acetate isobutyrate. 
     
     
         4 . The pressure sensitive adhesive composition of  claim 1 , wherein the one or more rheology and surface energy modifying agents is present in an amount effective to reduce a peel force of the transdermal delivery system by at least 30% compared to the peel force of the transdermal delivery system comprising the pressure sensitive adhesive composition that does not comprise the one or more rheology and surface energy modifying agents. 
     
     
         5 .- 8 . (canceled) 
     
     
         9 . A transdermal delivery system comprising:
 a backing layer, and   a reservoir laminated to the backing layer that comprises bupivacaine; 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 9 , 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 transdermal delivery system that comprises bupivacaine;   transdermally delivering the bupivacaine from the transdermal delivery system such that the following mean in vitro bupivacaine fluxes are achieved:   a mean in vitro bupivacaine flux ranging from about 0.1 to about 8 microgram/cm 2 /hr at about 12 hours after initiation of the transdermal delivery; and   a mean in vitro bupivacaine flux ranging from about 0.25 to about 6 microgram/cm 2 /hr at about 24 hours after initiation of the transdermal delivery.   
     
     
         24 . The method of  claim 23 , wherein the following mean in vitro bupivacaine flux is further achieved: a mean in vitro bupivacaine flux ranging from about 0.25 to about 6 microgramicm 2 /hr at about 48 hours after initiation of the transdermal delivery. 
     
     
         25 . The method of  claim 23 , wherein the following mean in vitro bupivacaine flux is further achieved: a mean in vitro bupivacaine flux ranging from about 0.25 to about 5 microgram/cm 2 /hr at about 72 hours after initiation of the transdermal delivery.