Transdermal delivery system

Abstract

A transdermal delivery system comprising a composition comprising a physiologically active agent and a penetration enhancer wherein the penetration enhancer comprises a combination of (i) an ester of salicylic acid, preferably selected from the C 6 to C 30 aliphatic ester of salicylic acid and (ii) polyethylene glycol (PEG) of average molecular weight no more than 300.

1 .- 22 . (canceled) 
     
     
         23 . A transdermal delivery system comprising a composition comprising:
 (a) a non-steroidal antiinflammatory agent;   (b) a penetration enhancer comprising a combination of (i) a C6 to C12 alkyl ester of salicylic acid in an amount from 0.1% to 10% by weight of the composition and (ii) a polyethylene glycol having an average molecular weight of no more than 300 in an amount from 0.5% to 20% by weight of the composition, wherein the weight ratio of the C6 to C12 alkyl ester of salicylic acid to the polyethylene glycol is from 10:1 to 1:10; and   (c) a volatile solvent selected from the group consisting of C2 to C4 alkanols in an amount from 40% to 95% by weight of the composition.   
     
     
         24 . A transdermal delivery system according to  claim 23 , wherein the non-steroidal antiinflammatory agent is selected from the group consisting of ibuprofen, flurbiprofen, ketoprofen, aclofenac, diclofenac, aloxiprin, aproxen, aspirin, diflunisal, fenoprofen, indomethacin, mefenamic acid, naproxen, phenylbutazone, piroxicam, salicylamide, salicylic acid, sulindac, desoxysulindac, tenoxicam, tramadol and ketoralac; salicylamide, salicylic acid, flufenisal, salsalate, triethanolamine salicylate, aminopyrine, antipyrine, oxyphenbutazone, apazone, cintazone, flufenamic acid, clonixeril, clonixin, meclofenamic acid, flunixin, colchicine, demecolcine, allopurinol, oxypurinol, benzydamine hydrochloride, dimefadane, indoxole, intrazole, mimbane hydrochloride, paranylene hydrochloride, tetrydamine, benzindopyrine hydrochloide, fluprofen, ibufenac, naproxol, fenbufen, cinchophen, diflumidone sodium, fenamole, flutiazin, metazamide, letimide hydrochloride, nexeridine hydrochloride, octazamide, molinazole, neocinchophen, nimazole, proxazole citrate, tesicam, tesimide, tolmetin, triflumidate, in racemic agent individual enantiomeric form. 
     
     
         25 . A transdermal delivery system according to  claim 23 , wherein the non-steroidal antiinflammatory agent is selected from the group consisting of ibuprofen, flurbiprofen, ketoprofen, aclofenac, diclofenac, aloxiprin, aproxen, aspirin, diflunisal, fenoprofen, indomethacin, mefanamic acid, naproxen, phenylbutazone, piroxicam, salicylamide, salicylic acid, sulindac, desoxysulindac, tenoxicam, tramadol, and ketorolac. 
     
     
         26 . A transdermal delivery system according to  claim 23 , wherein the non-steroidal antiinflammatory agent is selected from the group consisting of ibuprofen, diclofenac, ketoprofen, and naproxen. 
     
     
         27 . A transdermal system according to  claim 23 , wherein the non-steroidal anti-inflammatory agent is ibuprofen or diclofenac. 
     
     
         28 . A transdermal delivery system according to  claim 23 , wherein the volatile solvent is selected from the group consisting of ethanol, isopropanol, and mixtures thereof. 
     
     
         29 . A transdermal delivery system according to  claim 23 , wherein the volatile solvent is present in an amount in the range of from 60% to 95% by weight of the composition. 
     
     
         30 . A transdermal delivery system according to  claim 23 , wherein the composition further comprises a thickener. 
     
     
         31 . A transdermal delivery system according to  claim 23 , wherein the thickener is selected from the group consisting of polyacrylic acids, acrylic acid copolymers, agar, carrageenan, food starch, gelatins, gum Arabic, guargum, hydroxyethylcellulose, hydroxypropylmethyl cellulose, protein, and polyvinyl pyrrolidone. 
     
     
         32 . A transdermal delivery system according to  claim 30 , wherein the thickener is present in an amount of up to 5% by weight of the composition. 
     
     
         33 . A transdermal delivery composition according to  claim 23 , comprising from 5% to 45% by weight water. 
     
     
         34 . A transdermal delivery composition according to  claim 23 , comprising no more than 20% by weight water. 
     
     
         35 . A transdermal delivery system according to  claim 23 , wherein the C6 to C12 alkyl ester of salicylic acid is the ethylhexyl ester of salicylic acid. 
     
     
         36 . A transdermal delivery system according to  claim 23 , which is non-occlusive. 
     
     
         37 . A transdermal delivery system according to  claim 23 , wherein the PEG has an average molecular weight of 200. 
     
     
         38 . A transdermal delivery system according to  claim 23 , wherein the PEG has the formula H—[OCH2CH2]n-OH, wherein n is 4. 
     
     
         39 . A transdermal delivery system comprising a composition comprising:
 (a) a non-steroidal antiinflammatory agent selected from the group consisting of ibuprofen and diclofenac;   (b) a penetration enhancer comprising a combination of (i) a C6 to C12 alkyl ester of salicylic acid in an amount from 0.1% to 10% by weight of the composition and (ii) a polyethylene glycol having an average molecular weight of no more than 300 in an amount from 0.5% to 20% by weight of the composition, wherein the weight ratio of the C6 to C12 alkyl ester of salicylic acid to the polyethylene glycol is from 10:1 to 1:10; and   (c) a volatile solvent selected from the group consisting of ethanol, isopropanol and mixtures thereof in an amount from 50% to 95% by weight of the composition.   
     
     
         40 . A transdermal delivery system according to  claim 39 , wherein the PEG is PEG 200 or has the formula H—[OCH2CH2]n-OH, wherein n is 4. 
     
     
         41 . A transdermal delivery system according to  claim 40 , wherein the C6 to C12 alkyl ester of salicylic acid is the ethylhexyl ester of salicylic acid. 
     
     
         42 . A transdermal delivery system according to  claim 41 , wherein the weight ratio of ester of salicylic acid to polyethylene glycol of molecular weight no more than 300 is in the range of from 1:5 to 2:1. 
     
     
         43 . A transdermal delivery composition according to  claim 42 , wherein the PEG of molecular weight no more than 300 is present in an amount of from 0.5% to 10% by weight of the composition. 
     
     
         44 . A transdermal delivery system according to  claim 43 , wherein the ester of salicylic acid is present in an amount of from 0.5% to 5% by weight of the composition. 
     
     
         45 . A transdermal delivery system according to  claim 44 , wherein the C6 to C12 ester of salicylic acid is present in an amount in the range of from 0.5% to 5% by weight of the composition. 
     
     
         46 . A transdermal delivery system according to  claim 45 , wherein the volatile solvent comprises isopropanol. 
     
     
         47 . A transdermal delivery system according to  claim 45 , wherein the composition further comprises a thickener. 
     
     
         48 . A transdermal delivery system according to  claim 47 , wherein the thickener is selected from the group consisting of polyacrylic acids, acrylic acid copolymers, agar, carrageenan, food starch, gelatins, gum Arabic, guargum, hydroxyethylcellulose, hydroxypropylmethyl cellulose, protein and polyvinyl pyrrolidone 
     
     
         49 . A transdermal delivery system according to  claim 47 , wherein the thickener is present in an amount of up to 5% by weight of the composition.