Advances in Self-Nanoemulsifying Drug Delivery Systems: Mechanistic Insights and Formulation Strategies

Solubility enhancement is a significant challenge in oral drug delivery, particularly for Biopharmaceutical Classification System (BCS) Class II and IV drugs, which suffer from poor aqueous solubility. Lipid-based formulations, especially Self-Nanoemulsifying Drug Delivery Systems (SNEDDS), have gained attention as effective solutions to this problem. SNEDDS are isotropic mixtures of oil, surfactant, and co-surfactant/co-solvent that spontaneously form nanoemulsions upon contact with gastrointestinal fluids. This review provides a detailed exploration of the formulation, characterization, and solidification techniques of SNEDDS, emphasizing the roles of lipids, surfactants, and co-surfactants in enhancing drug solubility and bioavailability. The article discusses various evaluation techniques for SNEDDS, including droplet size analysis, in vitro dissolution testing, lipolysis, and permeability studies, which are crucial for assessing their performance. Additionally, the review examines the solidification methods of SNEDDS, including adsorption, spray drying, hot melt extrusion, and lyophilization, which enhance formulation stability and scalability. The review also highlights recent innovations in solid SNEDDS (S-SNEDDS), emphasizing their potential in delivering biologics, personalizing therapy, and improving patient compliance. This article positions SNEDDS as a versatile and robust platform capable of significantly enhancing the oral bioavailability of poorly soluble drugs, making them an attractive and reliable solution for modern drug delivery challenges and therapeutic advancements. Key words: SNEDDS (Self-nanoemulsifying drug delivery system), BCS (Biopharmaceutical Classification System), solubility enhancement, nanoemulsion, solidification techniques, bioavailability, self-emulsification, surfactants, co-surfactants, pseudo-ternary phase diagram.