Stability of nanosuspensions in drug delivery: mechanisms, characterization strategies, and advanced stabilization...

Poorly soluble drug delivery is a long-standing core challenge in the pharmaceutical field. With a drug loading capacity close to 100% and no requirement for carrier materials, nanosuspensions offer an ideal solution for delivering poorly soluble drugs. By reducing the drugs particle size to 100-500 nm, the nanosuspensions exhibited satisfied surface area and dissolution kinetics improvement. However, nanocrystals possess inherent thermodynamic and kinetic instability, driven by their high surface energy. The main stability problem is Ostwald ripening, aggregation, sedimentation, polymorphic transition, and chemical degradation. This instability has become a critical bottleneck limiting their industrialization and clinical translation. Compared with traditional trial-and-error methods, we systematically summarizes the core role of nanosuspensions stability in formulation development. It deeply analyzes the manifestations and intrinsic mechanisms of instability, and comprehensively outlines both traditional strategies and innovative technologies for improving stability. We focuses on the application progress of artificial intelligence, specifically in stability prediction, stabilizer screening, and process optimization. Novel stabilizer types, their action mechanisms, and research status are discussed in detail. At last, we reviewed current research challenges and prospects future development directions under the integration of multiple disciplines. This review delivers systematic theoretical support and practical guidance for the field. We hope these insights can help drive large-scale adoption of nanosuspension technology for poorly soluble drug delivery.