Abstract

Ezetimibe is a poorly water-soluble drug with varying bioavailability. The main objective of present work was to develop self nanoemulsifying drug delivery system (SNEDDS) for enhancing solubility and bioavailability of ezetimibe, which is widely used in treatment of homozygous familial hypercholesterolemia and homozygous sitosterolemia. The formulation of ezetimibe SNEDDS was optimized by simplex lattice design, multiple regression analysis and ternary contour plot. The optimal formulation of SNEDDS comprised of 7.058% oil (Oleic acid), 82.94% surfactant (Tween-80) and 10.0% co-surfactant (PEG-400). Pseudo-ternary phase diagrams were constructed to identify the efficient self-emulsification region. The average globule size of SNEDDS containing ezetimibe was about 90.63 nm when diluted with water. No significant variations in globule size and ezetimibe content in SNEDDS were observed over a period of 3 months at 40 ± 2° C/75 ± 5% RH and 25 ± 3° C (room temperature). In vitro diffusion studies showed remarkable increase in diffusion of drug. In vivo studies (in rats) showed significant increase in absorption of drug as compared to plain drug and marketed formulation. The data suggested use of SNEDDS to provide great potential as alternative to traditional oral formulations of ezetimibe.

Keywords: Ezetimibe, Self nanoemulsifying drug delivery system (SNEDDS), Simplex lattice design, globule size, Hyperlipidemia, Oleic acid, Tween-80, Polyethylene glycol-400, Zeta potential, In vivo pharmacokinetic