The solubility of metronidazole was determined in various aqueous-cosolvent and in aqueous-water soluble vitamin systems at 30 (+)(,-) 0.1 degree C. The aqueous-cosolvent system consisted of water and one of the following cosolvents

N,N-dimethyl acetamide, 1, 4-dioxane, ethanol, glycerin, glycofurol, polyethylene glycol and propylene glycol. It was found that the solubility of metronidazole increase with the concen trations of cosolvents, except in glycerin-water system where the solubility decrease with the concentrations of glycerin. Regular solution theory, the extended Hildebrand solubility approach and the log-linear solubility equations were compared to the experimental solubility data in order to find a mean of predicting solubilities of metronidazole and other drugs in these mixed solvents. These theoretical and semiempirical approaches are also useful in calculating the amount of cosolvent required. A large deviation from regular solution-theory was observed in all cosolvent systems. By using extended Hildebrand solubility approach, the interaction energy, W, of each mixed solvent is regressed against a polynomial equation expressed as a function of the solubility parameter, (...). The solubilities were back-calculated within < 20% (except in propylene glycol system) and with considerably better accuracy in most cases. The solubility parameter of metronidazole as determined from the peak solubility in mixed solvents varied from 10-15. It is suggested that the drug may have multiple orientations in mixed solvents. In general, the logarithmic increases in solubility (expressed as the ratio of the solubility in mixed solution, S, and in water, Sw) with increasing volume fraction of cosolvent, f, was observed. The experimental solubility data were fitted to a log-linear solubility equation, log S/Sw = (..), which gave a good linear fit up to 70% of cosolvent in all aqueous cosolvent systems. The solubility of metronidazole in aqueous-water soluble vitamins containing ranging concentrations of ascorbic acid, nicotinamide and pyridoxine hydrochloride were also increased with concentration of the vitamins. The hydrotophic effect may play an important role in enhancing aqueors sloubility of metronidazole. The parenteral dosage level of 50 mg/ml may be achieved by the use of 58% v/v dimethyl acetamide, 42% v/v 1, 4-dioxane, 67% v/v ethanol, 67% v/v glycofurol and 34% w/v nicotinamide. However, these concentrations are considerably high for parenteral use. Further investigation on multicosolvent systems is needed in order to find a system with lower concentration of cosolvents. The safety of these mixed solvents and each complete formula must be evaluated in animals and human before use.