Thermodynamic properties of a hypromellose acetate succinate (HPMCAS-L)-acetone-water system at temperatures below the glass transition temperature of HPMCAS-L were investigated. The solubility of water and acetone in HPMCAS-L is important for the optimization of spray-drying processes used in pharmaceutical manufacturing of solid dispersion formulations. Finite concentration data of each component were obtained separately using gravimetric sorption, differential pressure decay, and capillary column inverse gas chromatography. Results of thermodynamic properties were compared with prediction models based on the UNIQUAC functional-group activity coefficients (UNIFAC) method as well as the correlation model of Flory-Huggins. UNIFAC interaction parameters, modified to account for the interactions of water with the monosaccharide type groups in HPMCAS-L, had to be used in order to generate reasonable predictions. Overall, the Flory-Huggins model provided the best representation for both binary systems. (C) 2016 Elsevier B.V. All rights reserved.