Solid Dispersions: A Review on Instability, Improvement Methods and Future Development Directions

OBJECTIVE: 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.Significance: This review compares various stabilization approaches, highlighting their optimal applications and limitations to support broader SD market translation. RESULTS: 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. CONCLUSIONS: 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 IVIVC models is essential to bridge laboratory research and clinical application.