Formulation of self-emulsifying drug delivery systems

Abstract

Self-emulsifying drug delivery systems (SEDDS) are mixtures of oils and surfactants, ideally isotropic, sometimes including cosolvents, which emulsify under conditions of gentle agitation, similar to those which would be encountered in the gastro-intestinal tract. Hydrophobic drugs can often be dissolved in SEDDS allowing them to be encapsulated as unit dosage forms for peroral administration. When such a formulation is released into the lumen of the gut it disperses to form a fine emulsion, so that the drug remains in solution in the gut, avoiding the dissolution step which frequently limits the rate of absorption of hydrophobic drugs from the crystalline state. Generally this can lead to improved bioavailability, and/or a more consistent temporal profile of absorption from the gut. Ultra-low oil-water interfacial tension and/or substantial interfacial disruption are required to achieve self-emulsification. SEDDS are usually formulated with triglyceride oils and ethoxylated nonionic surfactants, usually at surfactant concentrations greater than 25%. In practice, disruption of the oil-water interface is caused by penetration of water into the formulation or diffusion of cosolvents away from the formulation. Both of these phenomena can be studied using equilibrium phase diagrams, which in combination with particle size measurements allow the optimisation of performance of SEDDS. The precise mechanisms of emulsification remain the subject of speculation but there is an empirical link between self-emulsification, liquid crystal formation, oil-water phase-inversion temperature and enhanced solubilization of water by oily formulations, and these phenomena are indicators of the efficiency of emulsification. This article describes strategies used for formulation of SEDDS, methods used for assessment of efficiency of emulsification and practical considerations regarding the use of SEDDS for enhancement of the bioavailability of drugs from the gastro-intestinal tract.