Methods and compositions for increasing solubility of azole drug compounds that are poorly soluble in water

Abstract

The combination of any two of a polyol, a polyol ether, and a low carbon organic alcohol provides a synergistic effect on the solubility of azole compounds, such as metronidazole, in aqueous fluid.

1 . (canceled) 
     
     
         2 . A pharmaceutical composition comprising:
 water;   an imidazole; and   at least two of a polyol, a polyol ether, and a low carbon organic alcohol.   
     
     
         3 . The pharmaceutical composition of  claim 2 , wherein the imidazole is metronidazole. 
     
     
         4 . The pharmaceutical composition of  claim 3 , wherein the pharmaceutical composition comprises metronidazole in an amount from about 1.25% (w/w) to about 1.5% (w/w). 
     
     
         5 . The pharmaceutical composition of  claim 2 , wherein the polyol is propylene glycol. 
     
     
         6 . The pharmaceutical composition of  claim 2 , wherein the polyol ether is diethylene glycol monoethyl ether. 
     
     
         7 . The pharmaceutical composition of  claim 2 , wherein the polyol ether is an ether of an alkylene glycol. 
     
     
         8 . The pharmaceutical composition of  claim 7 , wherein the ether of the alkyene glycol is polyethylene glycol. 
     
     
         9 . The pharmaceutical composition of  claim 8 , wherein the polyethylene glycol is polyethylene glycol 400 (“PEG 400”). 
     
     
         10 . The pharmaceutical composition of  claim 2 , wherein the low carbon organic alcohol is benzyl alcohol. 
     
     
         11 . The pharmaceutical composition of  claim 10 , wherein the pharmaceutical composition comprises benzyl alcohol in an amount of about 1% (w/w). 
     
     
         12 . The pharmaceutical composition of  claim 10 , wherein the pharmaceutical composition comprises benzyl alcohol in an amount of about 2% (w/w). 
     
     
         13 . The pharmaceutical composition of  claim 2 , wherein the pharmaceutical composition comprises water in an amount of at least about 55% (w/w). 
     
     
         14 . The pharmaceutical composition of  claim 2 , wherein the pharmaceutical composition comprises each of a polyol, a polyol ether, and a low carbon organic alcohol. 
     
     
         15 . The pharmaceutical composition of  claim 14 , wherein the polyol is propylene glycol, the polyol ether is diethylene glycol monoethyl ether, and the low carbon organic alcohol is benzyl alcohol. 
     
     
         16 . A method of treating a dermatologic or mucosal disorder that is responsive to treatment with an imidazole compound, the method comprising applying to an area of skin or mucosa of an individual having the dermatologic or mucosal disorder the pharmaceutical composition of  claim 2 .