Hot "Dissolving" Extrusion of Lurasidone with Natural Liquid Small Molecule for Amorphous Solid Dispersion Based Self-Assembled Submicron Emulsion.

Nowadays, about 90% of new drug candidates under development are poorly bioavailable due to their low solubility and/or permeability. Herein, w e introduce a natural liquid small molecule trans-anethole (TA) into drug-polymer system lurasidone (LUS)-poly (1-vinylpyrrolidone-co-vinyl acetate) (VA64), notably improving the compatibility of components for the successful preparation of amorphous solid dispersion (ASD) and facilitating the formation of self-emulsifying drug delivery system (SEDDS) during dissolution. LUS-TA-VA64 ASD shows enhanced supersaturation with a long maintenance time for at least 24 h over pure LUS. The strong non-covalent force between VA64 (as emulsifier) and TA (as oil phase)/ water promotes the self-assembly of submicron emulsion and ensures its stability for at least 10 h. Compared to the commercial salt form of LUS, the ASD shows 2-fold increase in peak plasma concentration (C max ) and area under plasma concentration-time profiles (AUC), 1.5-fold increase in peak time (T max ) and 2-fold decrease in AUC-based coefficient of variation (59%→26%) after single oral dose to rabbit. This article is protected by copyright. All rights reserved.