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

Area of Science:

• Pharmaceutical Sciences
• Materials Science

Background:

• Solid dispersions (SDs) are crucial for improving the bioavailability of poorly water-soluble drugs.
• Physical instability remains a significant barrier to the broader market translation of SD technology.

Purpose of the Study:

• To systematically review the structural characteristics, release mechanisms, and stability challenges of SDs.
• To identify key determinants of physical instability and summarize emerging stabilization strategies.
• To compare various stabilization approaches for optimal application and limitations.

Main Methods:

• Literature review of generational evolution, structural features, and characterization techniques of SDs.
• Analysis of the spring-parachute dissolution mechanism.
• Identification of four major drivers of physical instability: preparation parameters, humidity, kinetics, and thermodynamics.
• Discussion of recent stabilization strategies: ternary SD systems, drug loading control, and in vivo performance enhancement.
• Summary of emerging physicochemical descriptors and predictive models for formulation design.

Main Results:

• Four primary drivers of physical instability in solid dispersions were identified.
• Recent advancements include ternary SD systems, controlled drug loading, and enhanced in vivo performance.
• Emerging physicochemical descriptors and predictive models aid in rational formulation design.

Conclusions:

• Broader translation of SD technology is hindered by stability, excipient screening, high-dose formulation, and predictive dissolution models.
• Future progress necessitates integration of formulation design, process engineering, and predictive modeling (multifunctional polymers, advanced manufacturing, AI).
• Establishing biorelevant evaluation systems and robust in vitro-in vivo correlation (IVIVC) models is essential for clinical application.