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.