SEDDS and SMEDDS — Self-Emulsifying Systems
Self-Emulsifying Drug Delivery Systems, abbreviated SEDDS, and their finer-droplet variant, Self-Microemulsifying Drug Delivery Systems, abbreviated SMEDDS,...
Self-Emulsifying Drug Delivery Systems, abbreviated SEDDS, and their finer-droplet variant, Self-Microemulsifying Drug Delivery Systems, abbreviated SMEDDS, are isotropic mixtures of oil, surfactant, and co-surfactant or co-solvent that, upon exposure to aqueous gastrointestinal fluids under the gentle agitation provided by normal gut motility, spontaneously self-emulsify to form a fine oil-in-water emulsion, with resulting droplet sizes in the range of 100 to 300 nanometres for conventional SEDDS and below 100 nanometres for the more finely dispersed SMEDDS. These systems find their primary pharmaceutical application in the oral delivery of BCS Class II and Class IV drugs, where they can produce dramatic improvements in oral bioavailability by presenting the drug already in a solubilised, molecularly dispersed state at the point of intestinal absorption, circumventing the dissolution step that otherwise rate-limits absorption for poorly soluble compounds.
The rational design of a SEDDS formulation proceeds through the systematic screening of three component classes. Oil phase selection prioritises components offering high drug solubilising capacity, such as Labrafil M 1944CS, Labrafac PG, Cremophor EL, Labrasol, or oleic acid, since the oil serves as the primary drug reservoir within the formulation. Surfactant selection favours agents with a Hydrophile-Lipophile Balance value exceeding twelve, such as Tween 80, Cremophor RH40, or Labrasol, since these hydrophilic surfactants provide the principal thermodynamic driving force for spontaneous emulsification upon aqueous dilution. Co-surfactants or co-solvents, including Transcutol P, polyethylene glycol 400, propylene glycol, or ethanol, are incorporated to further reduce interfacial tension and droplet size, enhancing the overall efficiency and speed of the self-emulsification process.
Optimisation of SEDDS and SMEDDS formulations is conventionally guided by construction of a pseudo-ternary phase diagram, in which the relative proportions of oil, surfactant, and aqueous phase are systematically varied and the resulting phase behaviour recorded, allowing identification of the self-emulsification region — the zone of composition space within which spontaneous, clear microemulsion formation occurs upon aqueous dilution. Formulations selected from within this self-emulsification region are subsequently evaluated for droplet size, emulsification time, robustness to dilution, and drug loading capacity, before progressing to encapsulation, typically within a soft or hard gelatin capsule shell, for oral administration.