Effect of Polymer Type and Drug Loading on the Mechanism of Nano-Species Generation During Dissolution of Amorphous Solid Dispersions of Aprepitant

Dissolution of ASDs involves complex set of events, at the dissolving solid interface and dissolution medium. In situ nano-species formation during dissolution has attracted significant attention in recent years. ASDs of aprepitant, with two polymers - PVPVA and Eudragit L100 55, were generated at different drug loadings (DLs) of 5, 20 and 40%. PVPVA based ASDs demonstrated appearance of nano-species at 5 and 20% DL, due to ''amorphous amorphous phase separation'' (AAPS). Eudragit based ASDs at 5 and 20% DL also demonstrated nano-species formation primarily due to (i) Liquid Liquid Phase Separation (LLPS) in ''unstirred water layer' and secondarily, due to ion-pair complexation. The presentation highlights the 'switch-over' in the mechanism of nano-species formation from ASDs of aprepitant made using two different polymers. The outcomes shall help in designing ASDs with enhanced biopharmaceutical advantage.