Diclofenac topical formulation

Abstract

The present invention provides a gel formulation comprising diclofenac sodium which has superior transdermal flux properties, which may be used for the topical treatment of pain, such as in osteoarthritis.

1 . A topical composition, said topical composition comprising:
 (i) a non-steroidal anti-inflammatory drug (NSAID) or pharmaceutically acceptable salt thereof;   (ii) DMSO;   (iii) ethanol;   (iv) propylene glycol;   (v) optionally glycerol;   (vi) a thickening agent, wherein said thickening agent is selected from the group consisting of cellulose polymers, carbomer polymers, a carbomer derivative, a cellulose derivative, polyvinyl alcohol, poloxamers, polysaccharides, and mixtures thereof; and (vii) water.   
     
     
         2 . The topical composition of  claim 1 , wherein said NSAID or pharmaceutically acceptable salt thereof is present at 1-5% w/w; DMSO is present at 30-60% w/w; ethanol is present at 1-50% w/w; propylene glycol is present at 1-15% w/w; a thickener is present; and water is added to make 100% w/w, wherein said composition has a viscosity of 10-50,000 centipoise. 
     
     
         3 . The topical composition of  claim 2 , wherein said NSAID or pharmaceutically acceptable salt thereof is present at 2% w/w; DMSO is present at 45.5% w/w; ethanol is present at 23-29% w/w; propylene glycol is present at 11% w/w; the thickening agent is hydroxypropylcellulose and water is added to make 100% w/w, wherein said topical composition has a viscosity of about 500-5000 centipoise. 
     
     
         4 . The topical composition of  claim 1 , wherein said topical composition when applied to the skin has both a drying rate and transdermal flux greater than a comparative liquid formulation. 
     
     
         5 . The topical composition of  claim 4 , wherein said drying rate results in a residue of at most 50% of a starting amount after 24 hours and said transdermal flux is 1.5 greater than the comparative liquid formulation as determined by a Franz cell procedure. 
     
     
         6 . The topical composition of  claim 5 , wherein said Franz cell procedure is performed at finite dosing. 
     
     
         7 . The topical composition of  claim 5 , wherein said Franz cell procedure is performed at infinite dosing. 
     
     
         8 . The topical composition of  claim 1 , wherein said NSAID or pharmaceutically acceptable salt thereof degrades by less than 0.04% over the course of 6 months. 
     
     
         9 . The topical composition of  claim 1 , wherein said topical composition has a pH of 6.0-10.0. 
     
     
         10 . The topical composition of  claim 1 , wherein said topical composition when applied topically provides a reduction of pain over 12 weeks. 
     
     
         11 . The topical composition of  claim 10 , wherein said topical composition is applied twice daily. 
     
     
         12 . The topical composition of  claim 10 , wherein said pain is due to osteoarthritis. 
     
     
         13 . A method of treating pain, said method comprising the topical administration to said subject of a therapeutically effective amount of a topical composition comprising:
 (i) a non-steroidal anti-inflammatory drug (NSAID) or pharmaceutically acceptable salt thereof;   (ii) DMSO;   (iii) ethanol;   (iv) propylene glycol;   (v) optionally glycerol;   (vi) a thickening agent, wherein said thickening agent is selected from the group consisting of cellulose polymers, carbomer polymers, a carbomer derivative, a cellulose derivative, polyvinyl alcohol, poloxamers, polysaccharides, and mixtures thereof; and   (vi) water, to thereby treat pain.   
     
     
         14 . The method of  claim 13 , wherein said NSAID or pharmaceutically acceptable salt thereof is present at 1-5% w/w; DMSO is present at 30-60% w/w; ethanol is present at 1-50% w/w; propylene glycol is present at 1-15% w/w; a thickener is present; and water is added to make 100% w/w, wherein said topical composition has a viscosity of 10-50,000 centipoise. 
     
     
         15 . The method of  claim 14 , wherein said NSAID or pharmaceutically acceptable salt thereof is present at 2% w/w; DMSO is present at 45.5% w/w; ethanol is present at 23-29% w/w; propylene glycol is present at 11% w/w; the thickening agent is hydroxypropylcellulose; and water is added to 100% w/w, wherein said topical composition has a viscosity of about 500-5000 centipoise. 
     
     
         16 . The method of  claim 13 , wherein said topical composition when applied to the skin has both a drying rate and transdermal flux greater than a comparative liquid formulation. 
     
     
         17 . The method of  claim 16 , wherein said drying rate results in a residue of at most 50% of a starting amount after 24 hours and said transdermal flux is 1.5 or greater than the comparative liquid formulation as determined by a Franz cell procedure. 
     
     
         18 . The method of  claim 17 , wherein said Franz cell procedure is performed at finite dosing. 
     
     
         19 . The method of  claim 17 , wherein said Franz cell procedure is performed at infinite dosing. 
     
     
         20 . The method of  claim 13 , wherein said NSAID or pharmaceutically acceptable salt thereof degrades by less than 0.04% over the course of 6 months. 
     
     
         21 . The method of  claim 13 , wherein said topical composition has a pH of 6.0-10.0. 
     
     
         22 . The method of  claim 13 , wherein said topical administration provides a reduction of pain over 12 weeks. 
     
     
         23 . The method of  claim 22 , wherein said topical composition is applied twice daily. 
     
     
         24 - 37 . (canceled)