The utility of amorphization of drug molecules, such as enhanced solubility, dissolution rate and oral bioavailability, has been well exemplified in the literature. Yet, the application of this technique is often hindered by the crystallization liability of the drug. Amorphous solid dispersions (ASD), in which polymers are mixed with the amorphous drug, are often utilized to maintain the amorphous form. Several approaches have been illustrated in the literature to quantify the degree of mixing of drug and polymer. Although successful quantification has been demonstrated, all of these approaches probe the mixing energies at temperatures close to the melting temperature and, thus, require an extrapolation to room/storage temperature. Hence, an approach to directly estimate the drug-polymer extent of mixing at room temperature would enable a more accurate prediction of the physical stabilities. Herein, solution calorimetry was used to determine enthalpies of mixing of drug and polymer dispersions. These are necessary for the estimation of the Flory-Huggins interaction parameter, and associated free energy of mixing function. The estimated free energy of mixing, in turn, enabled the calculation of the drug solubility in the polymer system, which is a critical thermodynamic parameter in predicting the physical stability of an ASD. (C) 2017 Published by Elsevier Ltd.