Implications of Solution-Phase Phenomena and Nanodroplet Formation Upon Dissolution of Amorphous Dispersions in Aspirated Human Intestinal Fluids

Amorphous solid dispersions (ASDs) are supersaturating formulations that enhance both the apparent solubility, and the bioavailability of poorly water-soluble drugs following oral administration. Upon dissolution, ASDs can generate nano-sized amorphous droplets of ∼100-200 nm, when the concentration of the molecularly dissolved drug exceeds the amorphous solubility, thereby maximizing membrane transport rates during the supersaturation window, which can be observed in aspirated intestinal fluids similarly to simulated intestinal fluids.