Solubilizing of metronidazole

Abstract

Metronidazole is solubilized in an aqueous phase, by mixing same with niacinamide and at least two glycolic cosolvents; the resulting solutions and pharmaceutical compositions comprised thereof are useful for the treatment of dermatological conditions/afflictions, notably rosacea.

1 . A process for solubilizing metronidazole, the process comprising intimately admixing, in an aqueous phase, said metronidazole with niacinamide or salt thereof and at least two glycolic cosolvents, in the absence of cyclodextrin. 
   
   
       2 . The solubilization process as defined by  claim 1 , wherein the proportion of metronidazole, by mass relative to the total mass of the resulting solution, is greater than or equal to 0.75%. 
   
   
       3 . The solubilization process as defined by  claim 2 , wherein the proportion of metronidazole, by mass relative to the total mass of the resulting solution, is greater than or equal to 1%. 
   
   
       4 . A process for solubilizing metronidazole, the process comprising intimately admixing, in an aqueous phase, said metronidazole with niacinamide or salt thereof and at least two glycolic cosolvents, in the absence of cyclodextrin wherein the niacinamide/metronidazole molar ratio is less than 9. 
   
   
       5 . The solubilization process as defined by  claim 4 , wherein the niacinamide/metronidazole molar ratio is less than or equal to 5.5. 
   
   
       6 . The solubilization process as defined by  claim 1 , said glycolic cosolvents comprising propylene glycol and at least one polyethylene glycol. 
   
   
       7 . The solubilization process as defined by  claim 6 , said at least one polyethylene glycol comprising PEG 400. 
   
   
       8 . The solubilization process as defined by  claim 1 , wherein two glycolic cosolvents are admixed. 
   
   
       9 . The solubilization process as defined by  claim 8 , wherein said glycolic cosolvents are present in a ratio by mass of 1:1. 
   
   
       10 . A process for solubilizing metronidazole, the process comprising intimately admixing, in an aqueous phase, said metronidazole with niacinamide or salt thereof and at least two glycolic cosolvents, in the absence of cyclodextrin the process further comprising the following steps:
 a) preparing a solution of niacinamide in water, until complete dissolution of the niacinamide is attained,   b) introducing the glycolic cosolvents into the solution obtained in a),   c) homogenizing the solution obtained in b), and then adding a defined amount of metronidazole; and   d) after complete dissolution of the metronidazole, filtering the solution obtained.   
   
   
       11 - 21 . (canceled)