Liquid-liquid phase separation drug aggregate: Merit for oral delivery of amorphous solid dispersions

Abstract

As a promising strategy, amorphous solid dispersion has been extensively employed in improving the oral bioavailability of insoluble drugs. Despite the numerous advantages, the problems associated with supersaturation stability limit its further application. Recently, the formation and stability of the liquid-liquid phase separation drug aggregate (LLPS-DA) have been found to be vital for supersaturation maintenance. An in-depth review of LLPS-DA was required to further explore the supersaturation maintenance mechanism in vivo. Hence, this study aimed to present a short review to introduce the LLPS-DA, highlight the in vivo advantages for oral administration, and discuss the prospects to help understand the in vivo behavior of LLPS-DA.

Keywords: Amorphous solid dispersion; Drug aggregate; Liquid–liquid phase separation; Oral drug delivery; Permeability enhancement; Unstirred water layer.