SNEDDS containing bioenhancers for improvement of dissolution and oral absorption of lacidipine. I: Development and optimization

The aim of this study was to develop and optimize SNEDDS formulations containing surfactants reported to be bioenhancers for improvement of dissolution and oral absorption of lacidipine (LCDP). Preliminary screening was carried out to select proper components combination. D-optimal mixture experimental design was applied to optimize a SNEDDS that contains a minimum amount of surfactant, a maximum amount of lipid, and possesses enhanced emulsification and dissolution rates. Three formulation variables; the oil phase X1 (a mixture of Labrafil®/Capmul®), the surfactant X2 (a mixture of Cremophor®/Tween® 80) and the co-surfactant X3, were included in the design. The systems were assessed for droplet size, light absorbance, optical clarity, drug release and emulsification efficiency. Following optimization, the values of formulation components (X1, X2, and X3) were 34.20%, 40.41% and 25.39%, respectively. There is a good correlation between light absorbance and droplet size analysis of diluted SNEDDS (R2=0.883). Transmission electron microscopy demonstrated spherical droplet morphology. The stability of the optimized formulation was retained after storage at 40°C/75% RH for three months. The optimized formulation of LCDP showed a significant increase in dissolution rate compared to the drug suspension under the same conditions. Our results proposed that the optimized SNEDDS formulation, containing bioenhancing surfactants, could be promising to improve oral absorption of LCDP. © 2010 Elsevier B.V.