Effects of Heparin on Topical Use of Plasters Containing a Non-Steroidal Anti-Inflammatory Drug

Abstract

The present invention provides for a method of improving the release of non-steroidal anti-inflammatory drugs (NSAIDs) from a plaster or bandage comprising an adhesive layer with a pharmaceutically acceptable NSAID together with heparin or a heparinoid. The invention also provides for methods of reducing muscle hyperalgesia in subjects without spontaneous pain.

11 . A method of administering diclofenac from a transdermal patch containing diclofenac and heparin, the method comprising:
 topically applying a treatment transdermal patch containing diclofenac and heparin to the skin of a subject for no more than 24 hours,   wherein prior to the topical application, the treatment transdermal patch had been identified as having release characteristics comprising:
   (i) retention of all of the heparin after releasing diclofenac; and   (ii) release of a higher amount of diclofenac compared to a transdermal patch comprising diclofenac but not heparin,   
   
       by assessing an equivalent test transdermal patch containing diclofenac and heparin using an in vivo method that quantifies the relative release of diclofenac and heparin to demonstrate the release characteristics of the patches;
 wherein the treatment transdermal patch and the test transdermal patches each comprise:
 a substrate layer; 
 an adhesive layer in the form of a polymeric hydrogel matrix, the adhesive layer comprising:
 an effective amount of diclofenac or a pharmaceutically acceptable salt thereof, 
 sodium ethylenediamine tetraacetate, 
 heparin, 
 at least one thickening agent, 
 at least one wetting agent, and 
 at least one cross-linking agent; and 
 
 a protective film which can be removed at the moment of use; 
 
 wherein the in vivo method of quantifying the relative release of diclofenac and heparin from a transdermal patch comprises the steps:
 a) topically applying the test transdermal patch to the skin of a test subject for no more than 24 hours; 
 b) measuring residual content of diclofenac in the test transdermal patch after topical application to determine the amount of diclofenac released from the test transdermal patch; 
 c) measuring residual content of heparin in the test transdermal patch after topical application to determine the amount of heparin retained in the test transdermal patch; and 
 d) comparing the amount of diclofenac released with the amount of heparin retained in said transdermal patch. 
 
 
     
     
         12 . The method of  claim 11 , wherein the diclofenac or pharmaceutically acceptable salt thereof is diclofenac epolamine. 
     
     
         13 . The method of  claim 12 , wherein the effective amount of the diclofenac epolamine is between 0.1 and 5 wt % with respect to the hydrogel matrix. 
     
     
         14 . The method of  claim 13 , wherein the effective amount of the diclofenac epolamine is between 0.3 and 3 wt % with respect to the hydrogel matrix. 
     
     
         15 . The method of  claim 11 , wherein the concentration of the heparin is between 0.05 and 1 wt % with respect to the hydrogel matrix. 
     
     
         16 . The method of  claim 11 , wherein the subject has a minor soft tissue injury. 
     
     
         17 . The method of  claim 11 , wherein the subject has a minor strain, sprain, or contusion. 
     
     
         18 . The method of  claim 11 , wherein the amount of diclofenac or pharmaceutically acceptable salt thereof released from the test transdermal patch after 24 hours of topical application was determined to be about 3.6%. 
     
     
         19 . The method of  claim 11 , wherein the residual content of the heparin in the test transdermal patch was determined to be unchanged after 24 hours of topical application.