Physical Stability of Amorphous Solid Dispersions: a Physicochemical Perspective with Thermodynamic, Kinetic and Environmental Aspects.

Abstract

Amorphous solid dispersions (ASDs) have been widely used in the pharmaceutical industry for solubility enhancementof poorly water-soluble drugs. The physical stability, however, remainsone of the most challenging issues for the formulation development.Many factors can affect the physical stability via different mechanisms, and therefore an in-depth understanding on these factors isrequired. In this review, we intend to summarize the physical stability of ASDsfrom a physicochemical perspective whereby factors that can influence the physical stability areclassified into thermodynamic, kinetic and environmental aspects. The drug-polymer miscibility and solubility are consideredas the main thermodynamicfactors which may determine the spontaneity of the occurrence of the physical instabilityof ASDs. Glass-transition temperature,molecular mobility, manufacturing process,physical stabilityof amorphous drugs, and drug-polymerinteractionsareconsideredas the kinetic factors which areassociated with the kinetic stability of ASDs on aging. Storage conditions including temperature and humidity could significantly affect the thermodynamicand kineticstabilityof ASDs. When designing amorphous solid dispersions, it isrecommended that these thermodynamic, kinetic and environmental aspects should be completely investigatedand compared to establish rationale formulations for amorphous solid dispersions with high physical stability.