Extended Hildebrand solubility approach: solubility of theophylline in polar binary solvents

A quantitative approach is presented for predicting solubilities of crystalline compounds in binary solvent systems. The solubility of theophylline in mixed solvents consisting of dioxane and water was determined at 25 +/- 0.1 degrees. The solubilities across this range of polar solvents were back-calculated using a technique involving an interaction energy term, W. This parameter is regressed against a polynomial expression in delta 1, the solubility parameter for the mixed solvents. Except for the end-points, solubilities were predicted within less than 12% and with considerably better accuracy in most cases. The new approach modifies the well-known Hildebrand solubility equation to make it applicable to polar systems. Although the method may be used with solutes in pure solvents, its greatest application appears to be the prediction of drug solubility in binary solvent mixtures.