Formulation strategies for the development of high drug-loaded amorphous solid dispersions

Abstract

Amorphous solid dispersions (ASD) have gained tremendous attention over the past two decades as one of the most promising techniques for enhancing the solubility of poorly water-soluble drugs. However, low drug loading is one of the major challenges of ASD technology that limits its commercialization to only a few drug candidates. Increasing the drug loading increases the risk of recrystallization during storage (solid state) and/or during dissolution (solution state). Various formulation and process-related strategies have been explored that open the possibility of formulating high drug-loaded ASDs without the risk of recrystallization. Here, we review various formulation approaches, such as the use of surfactants, mesoporous silicas, polymer combinations, in situ thermal crosslinking, structural modification of polymeric carriers, and surface nanocoating using minerals. We also discuss the mechanisms by which these approaches inhibit solid state and/or solution state recrystallization.

Keywords: amorphous solid dispersions; high drug loading; mesoporous silicas; polymeric salts; recrystallization; surfactants.