Amorphous Solid Dispersions (ASDs) are mixtures of active pharmaceutical ingredients (APIs) and polymers aiming to increase API aqueous solubility and bioavailability. ASDs are often produced using solvent-based manufacturing, such as spray drying. Due to solubility or miscibility limitations in one solvent, solvent mixtures are frequently used for this purpose. Drying solvents or solvent mixtures from polymer-based products like ASDs is an energy-intensive and time-consuming process. Designing and optimising this drying process requires knowledge of the sorption isotherms of the solvent(s) in these polymer-based products. In this work, we developed a novel approach for measuring the simultaneous absorption/desorption of two solvents in a polymer. Combining classical dynamic vapour sorption (DVS) measurements with Raman spectroscopy, this innovative approach provides a more detailed and accurate measurement of the sorption isotherms than common methods. Moreover, we developed an approach for precisely predicting the sorption equilibria in three-component systems just based on sorption data of the corresponding binary subsystems. Our modelling approach combines the Perturbed-Chain Statistical Associating Fluid Theory (PC-SAFT) with the Non-Equilibrium Thermodynamics of Glassy Polymers (NET-GP). Building on the description of the sorption isotherms of either water or ethanol in poly(vinylpyrrolidone-co-vinyl acetate) (PVPVA64) and in indomethacin (IND), we were able to quantitatively predict the simultaneous sorption of water and ethanol in PVPVA64 and the one of ethanol in an IND/PVPVA64 ASD.
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