Transdermal delivery of ketoprofen polar derivates

Abstract

A topical or transdermal composition including a polar derivative of ketoprofen and a pharmaceutically acceptable topical or transdermal carrier, wherein the polar derivative of ketoprofen comprises a polarity that is greater than that of ketoprofen.

1 . A topical or transdermal composition comprising:
 (a) a polar ketoprofen derivative; and   (b) a pharmaceutically acceptable topical or transdermal carrier;   wherein the polar ketoprofen derivative comprises a polarity that is greater than that of ketoprofen.   
     
     
         2 . The composition of  claim 1 , wherein the polar ketoprofen derivative is a polar prodrug of ketoprofen. 
     
     
         3 . The composition of  claim 1 , wherein the polar ketoprofen derivative is an ester of ketoprofen. 
     
     
         4 . The composition of  claim 1 , wherein the polar ketoprofen derivative is represented by formula II: 
       
         
           
           
               
               
           
         
         wherein R is a polar substituent. 
       
     
     
         5 . The composition of  claim 4 , wherein R comprises at least one hydroxyl group. 
     
     
         6 . (canceled) 
     
     
         7 . The composition of  claim 1 , wherein the polar ketoprofen derivative is selected from the group consisting of alpha hydroxy acid ketoprofen derivatives, lactic acid ketoprofen derivatives and glycolic acid ketoprofen derivatives. 
     
     
         8 . (canceled) 
     
     
         9 . The composition of  claim 1 , wherein the polar ketoprofen derivative has a molecular weight that is less than about 1.3 times the molecular weight of ketoprofen. 
     
     
         10 . The composition of  claim 1 , wherein the polar ketoprofen derivative has a K OW  value that is lower than a K OW  value of ketoprofen, when measured under comparable conditions. 
     
     
         11 . The composition of  claim 1 , wherein the composition comprises a therapeutically effective amount of polar ketoprofen derivative. 
     
     
         12 . The composition of  claim 1 , further comprising ketoprofen. 
     
     
         13 . The composition of  claim 12 , comprising an amount of polar ketoprofen derivative that would be therapeutically effective in a corresponding composition comprising only polar ketoprofen derivative as the active ingredient, and an amount of ketoprofen that would be therapeutically effective in a corresponding composition comprising only ketoprofen as the active ingredient. 
     
     
         14 . The composition of  claim 12 , wherein at least one of the polar ketoprofen derivative and ketoprofen is present in an amount that would not be therapeutically effective in a corresponding composition comprising only ketoprofen derivative or ketoprofen as the active ingredient. 
     
     
         15 . The composition of  claim 12 , wherein both the ketoprofen derivative and ketoprofen are present in amounts that would not be therapeutically effective in a corresponding composition comprising only ketoprofen derivative or ketoprofen as the active ingredient. 
     
     
         16 . The composition of  claim 1 , comprising a mixture of polar ketoprofen derivatives. 
     
     
         17 . The composition of  claim 1 , further comprising at least one non-polar ketoprofen derivative. 
     
     
         18 . The composition of  claim 1 , wherein the pharmaceutically acceptable carrier is a topical carrier selected from liquids, creams, lotions, salves, balms, pastes, gels and ointments. 
     
     
         19 . The composition of  claim 1 , wherein the pharmaceutically acceptable carrier is a transdermal carrier comprising an adhesive selected from the group consisting of pressure-sensitive adhesives and bioadhesives. 
     
     
         20 . The composition of  claim 19 , wherein pharmaceutically acceptable carrier comprises an adhesive selected from the group consisting of pressure-sensitive silicone adhesives and pressure-sensitive acrylic adhesives, and mixtures of any two or more thereof. 
     
     
         21 . The composition of  claim 1 , wherein the pharmaceutically acceptable carrier is provided in a transdermal patch. 
     
     
         22 . The composition of  claim 1 , wherein the composition achieves a transdermal delivery rate of ketoprofen derivative that is at least about 20% of the delivery rate achieved by a corresponding composition comprising an equivalent amount of ketoprofen, when assessed under comparable conditions. 
     
     
         23 . A method of providing ketoprofen therapy comprising administering to a patient in need thereof a topical or transdermal composition comprising:
 (a) a polar ketoprofen derivative; and   (b) a pharmaceutically acceptable topical or transdermal carrier;   wherein the polar ketoprofen derivative comprises a polarity that is greater than that of ketoprofen.   
     
     
         24 . The method of  claim 23 , wherein the composition further comprises ketoprofen. 
     
     
         25 . The method of  claim 23 , wherein the composition further comprises a non-polar ketoprofen derivative.