Extended Hildebrand solubility approach: solubility of tolbutamide, acetohexamide, and sulfisomidine in binary solvent mixtures.

The extended Hildebrand approach for predicting solubilities of crystalline compounds in solvent mixtures was tested using tolbutamide, acetohexamide, and sulfisomidine in mixed solvents consisting of hexane-absolute ethanol and 95% (v/v) ethyl alcohol-aqueous buffer. The solubility of these drugs was determined at 25 +/- 0.2 degrees and then back-calculated using the adhesive energy term, W, to account for solute-solvent interaction. Solubilities were predicted within 13% for tolbutamide, 31% for acetohexamide, and 43% for sulfisomidine, and with considerably better accuracy in most solvent mixtures.