Amorphous Solid Dispersions for Poorly Water-Soluble Drugs:Formulation Strategies, Stabilisation Mechanisms and Recent Advances

Abstract

 Amorphous solid dispersions (ASDs) remain one of the most versatile and clinically validated formulation strategies for overcoming the poor aqueous solubility that affects a large proportion of new chemical entities and marketed drugs. By dispersing an active pharmaceutical ingredient at the molecular or colloidal level within a polymeric or, increasingly, mesoporous or co-amorphous carrier, ASDs generate a metastable, high-energy drug state capable of producing transient supersaturation and enhanced dissolution relative to the crystalline form. This review synthesises the literature published broadly between 2011 and 2022 on ASD formulation strategies, drug–polymer selection criteria, manufacturing technologies (spray drying, hot-melt extrusion, supercritical-fluid processing and electrospinning), stabilisation mechanisms, and characterisation approaches, with particular attention to recent advances in high-drug-loading systems, co-amorphous formulations, mesoporous-silica-based amorphisation, and artificial-intelligence-assisted formulation and stability prediction. Six comparative tables and four schematic figures consolidate key mechanistic and practical concepts, and the review concludes with a discussion of regulatory, Quality-by-Design and commercial considerations shaping the continued translation of ASD technology.