Drying kinetics of polymer-based pharmaceutical formulations

Amorphous solid dispersions (ASDs) are a popular method for increasing the oral bioavailability of active pharmaceutical ingredients (APIs) by molecularly dispersing them in a polymer. However, product inhomogeneity is often faced when preparing ASDs using solvent-based manufacturing processes such as spray drying. In this work, we considered the drying of an ASD composed of poly-(vinylpyrrolidone-co-vinyl acetate) (PVPVA64) and indomethacin (IND) from solutions containing both ethanol and water. The Perturbed-Chain Statistical Associated Fluid Theory (PC-SAFT) allowed the prediction of suitable feed compositions, which results in homogeneous solutions during the entire drying process. The predicted drying curves, which show the development of the ASD-solution composition during drying, were found in excellent agreement with the experimental data. As a key outcome, we developed a novel framework that allows us to also model the drying kinetics of two-solvent ASD solutions. This framework was applied to accurately predict the drying kinetics of a polymer and an ASD from solutions containing both water and ethanol starting from various feed solutions just based on single-solvent drying data of the pure polymer.