Design and optimization of self-nanoemulsifying drug delivery systems of clove oil for efficacy enhancement in fish anesthesia

Self-nanoemulsifying drug delivery system (SNEDDS) is an efficient system for delivering water-insoluble compounds. The aim of this study was to develop SNEDDS containing clove oil (C-SNEDDS) to increase clove oil aqueous miscibility and for fish anesthesia. C-SNEDDS was prepared using different lipids and surfactants. An axial extended design was used to select suitable components. The effects of components on dispersing time, droplet size, and size distribution of the dispersed C-SNEDDS were investigated. D-optimal experimental design, multiple linear regression, and partial least squares regression were employed to optimize the formulation variables, X1 (clove oil), X2 (lipid), and X3 (surfactant) for preparing high clove oil loading C-SNEDDS. Clove oil and surfactant showed a significant effect on the droplet size. Spherical droplets could be observed under cryogenic transmission electron microscopy from the small-size dispersed C-SNEDDS. C-SNEDDS using 1:1 ratio of Captex-Capmul and Kolliphor EL showed high clove oil loading of 35–36%. The droplet size demonstrated a high impact on the induction time to anesthesia but not on the recovery time. The dispersed C-SNEDDS with an average droplet size of 58.2 ± 0.9 nm significantly showed a fast induction time of approximately 2.5 min, 2-fold significantly faster than MS-222.