Transdermal Delivery Systems for Sufentanil

Abstract

Transdermal delivery systems for administering sufentanil through the skin are provided. The systems contain a sufficient amount of sufentanil to induce and maintain a constant state of analgesia when applied to a subject. The systems are characterized as having one or more features including a high degree of dosage form rate control over flux of sufentanil from the system, a high net flux of sufentanil from the system through the skin, lack of a permeation enhancer, an adhesive member demonstrating superior shear time, a low coefficient of variation in the net flux of sufentanil from the system, a high delivery efficiency, and a substantially constant steady state net flux of sufentanil from the system. Methods of using the transdermal delivery systems to administer a sufficient amount of sufentanil to induce and maintain analgesia for extended periods when applied to a subject are also provided.

1 .- 111 . (canceled) 
     
     
         112 . A transdermal delivery system, comprising a pressure-sensitive adhesive matrix comprising:
 both dissolved and undissolved sufentanil, and   a blend of high molecular weight polyisobutylene and low molecular weight polyisobutylene, the high molecular weight polyisobutylene having a viscosity average molecular weight of about 450,000 to 2,100,000, the low molecular weight polyisobutylene having a viscosity average molecular weight of about 1,000 to 450,000.   
     
     
         113 . The system of  claim 112 , wherein the matrix has a solubility for sufentanil of about 1 wt % to about 2 wt %. 
     
     
         114 . The system of  claim 112 , wherein the sufentanil is present in the system in an amount of about 1 wt % to about 20 wt % relative to the total system. 
     
     
         115 . The system of  claim 112 , wherein the low molecular weight polyisobutylene has a viscosity average molecular weight of about 50,000 to 55,000. 
     
     
         116 . The system of  claim 112 , wherein the high molecular weight polyisobutylene has a viscosity average molecular weight of about 1,100,000. 
     
     
         117 . The system of  claim 112 , further comprising plasticizer. 
     
     
         118 . The system of  claim 112 , further comprising polybutene. 
     
     
         119 . The system of  claim 112 , further comprising filler. 
     
     
         120 . The system of  claim 112 , further comprising silicon dioxide. 
     
     
         121 . The system of  claim 112 , further comprising a backing. 
     
     
         122 . The system of  claim 112 , further comprising an occlusive backing. 
     
     
         123 . The system of  claim 112 , further comprising a release liner. 
     
     
         124 . The system of  claim 112 , wherein the system does not comprise a rate controlling membrane. 
     
     
         125 . The system of  claim 112 , wherein the system does not comprise permeation enhancer. 
     
     
         126 . The system of  claim 112 , wherein the system, when applied to a subject as a single patch, provides delivery of sufentanil over a single application administration period of 7 days sufficient to establish and maintain a plasma sufentanil concentration having a maximum to minimum ratio of about 1.8 or less over the administration period. 
     
     
         127 . The system of  claim 112 , wherein the system provides substantially zero order delivery rate of sufentanil over a single application administration period of at least about 48 hours. 
     
     
         128 . The system of  claim 112 , wherein the system, when applied to a subject over a single application administration period, provides sustained analgesia in the subject for 3 or more days by delivery of sufentanil from the system with a coefficient of variation (ΔJ N /J N ) of about 50% or less. 
     
     
         129 . The system of  claim 112 , wherein the system provides dosage form rate control (J N /J D ) over flux of sufentanil from the system of at least about 50%. 
     
     
         130 . The system of  claim 112 , wherein the delivery rate at steady state is at least about 1 μg/hour. 
     
     
         131 . The system of  claim 112 , wherein net flux from the system through the skin is at least about 1 μg/cm 2 /hour.