Self-Nanoemulsifying Drug Delivery Systems in Soft Gelatin Capsules: Formulation Advances, Manufacturing Challenges, and Future Perspectives

Poor aqueous solubility remains a major barrier to the successful oral delivery of a large proportion of newly discovered drug candidates, often resulting in low and variable bioavailability. Self-nanoemulsifying drug delivery systems (SNEDDS) have emerged as a robust formulation strategy to address these limitations by forming fine oil-in-water nanoemulsions upon mild agitation in gastrointestinal fluids. When incorporated into soft gelatin capsules, SNEDDS offer additional advantages, including accurate dose delivery, improved patient compliance, and enhanced protection of labile drug substances. This review provides a comprehensive overview of self-nanoemulsifying formulations specifically designed for soft gelatin capsule filling, with emphasis on formulation principles, excipient selection, and critical quality attributes governing performance. Key aspects of SNEDDS characterization, encompassing physicochemical, in vitro, and in vivo evaluation techniques, are discussed in relation to capsule compatibility, stability, and biopharmaceutical behavior. Furthermore, industrial manufacturing considerations, scale-up challenges, and regulatory expectations relevant to SNEDDS-filled soft gelatin capsules are critically examined. Current limitations, such as capsule shell interactions, precipitation risks, and long-term stability concerns, are highlighted alongside emerging technological advances, including supersaturable systems, lipid-based excipient innovations, and predictive in vitro-in vivo correlation approaches. Overall, this review underscores the evolving role of SNEDDS in soft gelatin capsule dosage forms and outlines future prospects for their expanded application in improving the oral delivery of poorly soluble drugs. Keywords: Self-nanoemulsifying drug delivery; Soft gelatin capsules; Nano emulsions; Stability and Regulatory considerations