Water-Assisted Drying of PVPVA-Based Amorphous Solid Dispersions

Drying amorphous solid dispersions (ASDs) often requires a secondary drying step, as after the first drying step, residual solvent usually remains in the ASD. Enhancing the secondary drying step of ASDs is a critical task, as it is essential to ensure that the residual solvent content meets regulatory limits. The challenge lies in the slow drying of the glassy ASD at very low solvent contents. This study performs a water-assisted drying approach that (1) accelerates residual solvent removal and (2) reduces the solvent content in the final ASD. The proposed approach involves maintaining a constant relative humidity (RH) during ASD drying, in contrast to conventional drying, which applies dry air or vacuum. We employed dynamic vapor sorption with integrated Raman spectroscopy as an analytic method to measure the water-assisted secondary-drying kinetics of ASDs at low residual solvent contents. An ASD of indomethacin and poly vinylpyrrolidone-<i>co</i>-vinyl acetate (PVPVA) containing residual amounts of ethanol was dried at 30 °C using both water-assisted and conventional drying approaches. Compared to the conventional drying, where 3.5 wt % ethanol remained in the ASD even after 1500 min, water-assisted drying at RH = 0.8 could completely remove the ethanol from the ASD in the same time frame. Modeling the ASD solution in advance using PC-SAFT (perturbed-chain statistical associating fluid theory) enabled the selection of starting compositions, preventing water-induced phase separation during the drying process. Moreover, applying the nonequilibrium (NE) version, NE-PC-SAFT, we accurately predicted the composition of the ASD solution during drying. Furthermore, we were able to predict the RH at which the residual ethanol content could be entirely removed from the ASD in a given time frame.