Solid dispersions: a review on instability, improvement methods, and future development directions

To systematically review the structural characteristics, release mechanisms, and stability challenges of solid dispersions (SDs), identifying key determinants of physical instability and summarizing emerging stabilization strategies.

This review compares various stabilization approaches, highlighting their optimal applications and limitations to support broader SD market translation.

The generational evolution, structural features, and characterization techniques of SDs are outlined, along with the spring-parachute dissolution mechanism. Four major drivers of physical instability are identified: preparation-related parameters, humidity-induced phase separation, kinetic factors, and thermodynamic factors. Recent stabilization strategies-including ternary SD systems, drug loading control, and in vivo performance enhancement-are discussed. Emerging physicochemical descriptors and predictive models for rational formulation design are also summarized.

SD technology remains critical for improving bioavailability of poorly water-soluble drugs, but broader translation is limited by system-dependent stability, inefficient excipient screening, high-dose formulation challenges, and limited predictive dissolution models. Future progress requires integrating formulation design, process engineering, and predictive modeling, including multifunctional polymers, advanced manufacturing (e.g. hot-melt extrusion), and digital tools based on molecular simulation and AI. Establishing biorelevant evaluation systems and robust in vitro-in vivo correlation (IVIVC) models is essential to bridge laboratory research and clinical application.