SNEDDS as a Drug Delivery Carrier for BCS Class III and IV Drugs

Self-Nanoemulsifying Drug Delivery Systems (SNEDDS) are lipid-based systems for drug delivery characterized by poor aqueous solubility and/or limited intestinal permeability, which are overcome by the spontaneous formation of nanosized oil-in-water emulsions upon exposure to gastrointestinal fluids. The progress of SNEDDS over the past years has led to higher levels of solid SNEDDS, supersaturable formulations, and multifunctional platforms incorporating bioenhancers to address both solubility- and permeability-limited absorption, particularly for Biopharmaceutics Classification System (BCS) Class III and IV drugs. This review critically summarizes and synthesizes key developments reported between 2020 and 2025, with emphasis on formulation strategies, mechanistic insights, biorelevant evaluation approaches, and translational considerations. Recent evidence also suggests that optimised SNEDDS may lead to improved drug solubilisation, modification of intestinal membrane permeability, inhibition of efflux transporters, and reduced presystemic metabolism, translating into improved and more consistent oral bioavailability. Preclinical and emerging clinical studies have shown increased systemic exposure, decreased pharmacokinetic variability, and, in some cases, further improved therapeutic outcomes across diverse drug classes. The significance of solidification technologies, digestion-aware formulation design, and quality-by-design frameworks as factors to enhance scalability and achieve reproducibility has also emerged from the review. Nevertheless, despite such great progress, there are still challenges, such as physiological variability in gastrointestinal conditions, surfactant-related tolerability, stability during storage and digestion, regulatory considerations, and the requirement for robust in vitro and in vivo translational models to be established. Taken together, SNEDDS represent a flexible and evolving platform for oral delivery of challenging drug candidates, with continued innovation expected to support their broader clinical translation.