Thermodynamics of solutions. II. Flurbiprofen and diflunisal as models for studying solvation of drug substances.

Three independent methods (sublimation, solubility and solution calorimetry) were used to study the dissolution and solvation processes of diflunisal (DIF) and flurbiprofen (FBP). Thermodynamic functions for the sublimation of DIF and FBP were obtained. Concentrations of saturated solutions and standard solution enthalpies of DIF and FBP in aliphatic alcohols and individual organic solvents were measured. Correlation analysis between: (a) the thermodynamic functions for a substance in various solvents, and (b) the same functions for different compounds was carried out. The investigated substances can be arranged with increasing Gibbs energy of solvation as follows: benzoic acid<DIF<FBP. Enthalpy is found to be the major driving force of the solvation process for all the studied compounds. The ratio of specific and nonspecific solute-solvent interaction in terms of enthalpies (epsilon (H)) and in terms of entropies (epsilon (S)) was analyzed. Based on the experimental data, a compensation effect of thermodynamic solubility functions of the investigated substances both in alcohols and in organic solvents was found.