Recent progress in supersaturation-based SNEDDS: Formulation, mechanism, and biopharmaceutical performance

This review highlights supersaturation-based SNEDDS (self-nanoemulsifying drug delivery systems), focusing on formulation strategies, supersaturation generation, stabilization mechanisms, and their impact on drug release, permeation, and bioavailability. The discussion is based on articles from reputable databases published between 2020 and 2025. Supersaturation-based SNEDDS are classified into supersaturable and supersaturated types, differing in the onset of supersaturation and approaches to precipitation inhibition. Widely developed for BCS Class II and IV drugs, these systems increase thermodynamic activity and enhance drug absorption in the gastrointestinal tract. Although metastable and prone to precipitation, precipitation inhibitors (PIs) such as HPMC or PVP can stabilize the supersaturated state, suppressing nucleation and crystal growth. Proper screening is essential to identify the most suitable PIs for each formulation. Supersaturable and supersaturated SNEDDS have improved drug release and intestinal permeation, enhancing bioavailability compared to pure drugs, conventional SNEDDS, or marketed formulations.