Decoding excipients in lipid-based self-emulsifying drug delivery systems: Insights into physicochemical properties...

Enhancing the oral delivery of poorly water-soluble drugs remains a key challenge in pharmaceutical development. Lipid-based self-emulsifying drug delivery systems (SEDDS) offer a promising approach by improving drug solubilization, absorption, and bioavailability. Central to their performance is the physicochemical profile of excipients - such as lipids, surfactants, and cosurfactants - which govern critical aspects of formulation behavior. Parameters like hydrophilic-lipophilic balance (HLB), polarity, viscosity, and interfacial tension directly influence drug loading, self-emulsification capacity, droplet size, and colloidal stability. These properties also dictate intermolecular interactions at the oil-water interface, impacting thermodynamic stability and emulsification kinetics. Understanding these physicochemical interactions is indispensable for rational system design and successful translation to clinical outcomes. This review integrates and analyzes recent findings on how specific excipient characteristics modulate the structure, dynamics, and performance of SEDDS. Advances such as supersaturable SEDDS and mucoadhesive systems, along with solidification technologies (e.g., spray drying, adsorption, 3D printing), expand the applicability and stability of these formulations. By consolidating knowledge on excipient-function relationships, this review provides a strategic framework for the selection and combination of excipients tailored to drug properties and therapeutic goals. A deep understanding of these physicochemical parameters and their synergistic interactions is crucial for optimizing self-emulsifying formulations that are stable, efficient, and clinically effective.