Author(s): Vijay Rajaram Mahajan*, Ganesh Dinkar Basarkar, Chandrashekhar Devidas Upasani
The present work was aimed at formulating a SMEDDS self-micro emulsifying drug delivery system) of Ezetimibe and evaluating its in vitro and in vivo activity. Ezetimibe belongs to a new class of lipid-lowering agents that selectivity inhibits the intestinal absorption of cholesterol and related plant sterols. Due to very low solubility in the aqueous media ezetimibe shows low bioavailability. The aim of the present study investigation was to develop a Lipid Based Formulation (LBF) to enhance the dissolution as well as the oral bioavailability of practically water insoluble Ezetimibe. Type I & Type IV LBF formulation was prepared and evaluated. Solubility of the drug in different oils, Surfactant & co-surfactant was determined. On the basis of the solubility of the ezetimibe in different oil, surfactant & co-surfactant. Type I & Type IV formulation was prepared in Capriyol 90 (83 mg/ml), Capmul MCM C8 (73.7783 mg/ml) & Cremophor RH 40 (260 mg/ml), Cremophor EL (148 mg/ml), Acysol K 140 (327 mg/ml), Acrysol EL 135 (138 mg/ml), combination of various surfactants with PEG 400. Lipid based formulation then further evaluated for its percentage transmittance, robustness to dilution, stability and drug content. The optimized formulation of Ezetimibe loaded in Lipid based formulation shows complete in vitro drug release in 20min while drug shows only 25.5% drug release in 90 min. In Vitro study proved that the potential use of Lipid based formulation improves the dissolution rate of poorly water-soluble drug-Ezetimibe. Comparative pharmacodynamic evaluation was investigated in terms of lipid- lowering efficacy, using a Triton WR 1339-induced hypercholesterolemia model in rats. The SMEDDS formulation significantly reduced serum lipid levels in phases I and II of the Triton WR 1339 test, as compared with plain Ezetimibe. The optimized formulation was then subjected to stability studies as per International Conference on Harmonization (ICH) guidelines and was found to be stable over 12 months. Thus, the study confirmed that the SMEDDS formulation can be used as a possible alternative to traditional oral formulations of Ezetimibe to improve its bioavailability.