Abstract
Improved dissolution and oral absorption of widely known taxane-paclitaxel was accomplished using self emulsification approach and P-glycoprotein (P-gp) modulating excipients. The formulation components i.e., oil, surfactant and co-surfactant were investigated for their interactive effect. Box-Behnken experimental design was employed to optimize the formulation variables, X-1 as oil phase (Propylene glycol monocaprylate and glyceryl monooleate), X-2 as surfactant (Polyoxyethylene 20 sorbitan monooleate and polyoxyl 15 hydroxystearate), and X-3 as cosurfactant (Diethylene glycol monoethyl ether and polyethylene glycol 300). Formulations were assessed for parameters such as solvent capacity, droplet size and in-vitro release. Observations revealed Diethylene glycol monoethyl ether as a good solubilizer for paclitaxel. Surfactant/cosurfactant mass ratio (Km) played a significant influence on formation of self-emulsifying system of nano-dimension. Km value 2 was observed to exert a synergistic effect. A good correlation was observed between percent cumulative drug release of self nanoemusifying system (SNES) and droplet size analysis (R-2 = 0.893). The time course of absorptive transport of drug loaded self emulsifying system across small intestine in everted gut sac study was found to be 11.32 folds high. Confocal laser scanning showed much deeper permeation of the optimized formulation across the intestine. Lactate dehydrogenase (LDH) activity of intestinal tissues treated with formulation and pure drug solution confirmed that the developed formulation is safe and effective carrier for oral delivery of paclitaxel.