Research on Solubility Measurement, Solvent Effects, Preferential Solvation, and Model Correlation of Sofosbuvir Form A in Different Pure and Binary Solvents

Solubility property is crucial to pharmaceutical development, form screening, and the production control of drugs. In this work, the equilibrium of sofosbuvir form A in different solvents was established, and the solubility was determined using isothermal saturation methods. The solvent effect, preferential solvation, and model correlation were investigated. The mole fraction solubility of sofosbuvir form A enhanced as the temperature increased. The mole fraction solubility was arranged in the following order acetone > ethanol > 1-butanol > acetonitrile > ethyl acetate > water > toluene > cyclohexane. The solvent effect results indicated that the hydrogen bond interactions were vital to dissolution of sofosbuvir form A. For mixture systems, the solubility enhanced with the increase of the acetone/ethanol composition. The preferential solvation was evaluated using a dimensionless parameter (delta) and the equilibrium constant of the solvent exchange process (K-ps). The results indicated that acetone or ethanol dissolved sofosbuvir preferentially. Besides, Apelblat, lambda h, Wilson, Jouyban-Acree, and Apelblat-Jouyban-Acree models were used to correlate the solubility data. The maximum values of relative average deviation and root mean square deviation were calculated to be 2.74% and 9.63 x 10(-4) in monosolvents and 1.38% and 3.47 x 10(-4) in mixed solvents, respectively. These models exhibited good correlation with the solubility results of sofosbuvir form A.