Aqueous compositions containing metronidazole

Abstract

An aqueous solution of metronidazole in which the concentration of metronidazole is higher than 0.7%. The solution contains a combination of solubility-enhancing agents, one of which is niacinamide. Methods of manufacture and therapeutic use of the solution are disclosed.

1 . A method for increasing the solubility of metronidazole in an aqueous fluid comprising combining in the aqueous fluid metronidazole, a first metronidazole solubility enhancer, and a second metronidazole solubility enhancer, wherein the concentration of metronidazole that is combined in the aqueous fluid is higher than the saturated dissolved soluble concentration of metronidazole in the aqueous fluid in the absence of the first and/or second solubility enhancers, wherein the concentration of the first solubility enhancer in the aqueous fluid is higher than its saturated dissolved soluble concentration in the aqueous fluid in the absence of the second solubility enhancer, and wherein the second solubility enhancer is niacinamide at a concentration that is sufficient, in combination with the first solubility enhancer, to increase the dissolved concentration of metronidazole in the aqueous fluid above the saturated dissolved concentration of metronidazole in the absence of the first and second solubility enhancer and that is sufficient to increase the solubility of the first solubility enhancer in the aqueous solution above its solubility in the aqueous fluid in the absence of niacinamide. 
     
     
         2 . The method of  claim 1  wherein the aqueous fluid is at a temperature of 5 degrees celsius. 
     
     
         3 . The method of  claim 2  wherein the dissolved concentration of metronidazole in the aqueous fluid is between 0.7% and 1.0% w/w. 
     
     
         4 . The method of  claim 1  wherein the concentration of metronidazole that is dissolved in the aqueous fluid is higher than that which is dissolvable in the aqueous fluid in the absence of either the first or the second solubility enhancers. 
     
     
         5 . The method of  claim 1  wherein the first solubility enhancer is betacyclodextrin. 
     
     
         6 . A pharmaceutical composition comprising an aqueous solution comprising an aqueous fluid, metronidazole, a first solubility enhancer, and a second solubility enhancer which is niacinamide, wherein the concentration of metronidazole in the aqueous solution is higher than the saturated solubility of metronidazole in the aqueous fluid in the absence of either or both of the first and second solubility enhancers, wherein the concentration of the first solubility enhancer in the aqueous fluid is higher than its saturated solubility in the aqueous solution in the absence of the second solubility enhancer, and wherein the concentration of the second solubility enhancer is sufficient to increase the solubility of the first solubility enhancer in the aqueous fluid above its saturated solubility in the absence of the second solubility enhancer. 
     
     
         7 . The pharmaceutical composition of  claim 5  which is at a temperature of 5 degrees celsius. 
     
     
         8 . The pharmaceutical composition of  claim 5  wherein the first solubility enhancer is betacyclodextrin.