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

Purpose Amorphous solid dispersions (ASDs) have been widely used in the pharmaceutical industry for solubility enhancement of 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. Methods In this review, we intend to summarize the physical stability of ASDs from a physicochemical perspective whereby factors that can influence the physical stability are classified into thermodynamic, kinetic and environmental aspects. Results The drug-polymer miscibility and solubility are considered as the main thermo dynamic factors which may determine the spontaneity of the occurrence of the physical instability of ASDs. Glass-transition temperature, molecular mobility, manufacturing process, physical stability of amorphous drugs, and drug-polymer interactions are considered as the kinetic factors which are associated with the kinetic stability of ASDs on aging. Storage conditions including temperature and humidity could significantly affect the thermodynamic and kineticstability of ASDs. Conclusion When designing amorphous solid dispersions, it is recommended that these thermodynamic, kinetic and environmental aspects should be completely investigated and compared to establish rationale formulations for amorphous solid dispersions with high physical stability.