Multiple solubility maxima of oxolinic acid in mixed solvents and a new extension of Hildebrand solubility approach

A new extension of the Hildebrand solubility approach which describes drug solubility in solvent mixtures showing multiple solubility peaks, the chame leonic effect, is proposed. The experimental solubilities of oxolinic acid were measured at 25 OC in solvent mixtures of ethanol-water and ethanol-eth yl acetate, A plot of the mole fraction of the drug against the solubility parameter (delta) of the solvent mixtures displays two peaks at delta=30.78 MPa1/2 (80% v/v of ethanol in water) and at delta=20.90 MPa1/2 (30% v/v of ethanol in ethyl acetate), The new extension proposed reproduces two solub ility peaks. The thermograms of the solid phase before and after equilibrat ion with the solvent mixtures did not show significant changes, The new ext ension was also tested with experimental data previously reported for drugs showing two solubility peaks of different height, The accuracy of other pu blished models for describing two solubility maxima is also compared.