Potential Investigation of Peceol for formulation of Ezetimibe self nano emulsifyingDrug Delivery Systems

Abstract

The present work was aimed at formulating and physicochemical characterization SNEDDS (self Nano emulsifying drug delivery system) of ezetimibe and evaluating its in vitro and in vivo potential. The solubility of both drugs was determined in excipient screening studies. Pseudoternary phase diagrams were used to evaluate the Nano emulsification existence area, composed of different surfactants, co surfactants, and oils at different surfactant to-cosurfactant (S/CoS) ratios, and the system exhibiting the largest percentage area of the self-Nano emulsifying region was selected and optimum oil ratio in the SNEDDS was selected by evaluating the clarity, precipitation and mean droplet size of the resultant Nanoemulsions. The release rate of ezetimibe was investigated using an in vitro dissolution test. In vitro dissolution studies showed that the SNEDDS composed of Peceol (20% wt/wt), Tween 80 (30% wt/wt), Ethanol (30% wt/wt), and ezetimibe (20% wt/wt) had higher initial dissolution rates for both drugs when compared with plain EZT. More importantly, EZT SNEDDS had a significantly increased dissolution profile in distilled water and pH 4.0 acetate buffer, implying enhanced bioavailability. The underlying mechanism of the loading capacity of EZT was elucidated by measurement of the zeta potential analysis. The results implied that EZT was located both in the Nanoemulsion core and the surfactant–cosurfactant layer. Comparative pharmacokinetic evaluation of EZT SNEDDS was investigated in terms of C max, tmax and AUC using rats. The SNEDDS formulation significantly increases pharmacokinetics parameter as compared with plain ezetimibe. The optimized formulation was then subjected to stability studies and was found to be stable over 6 months. Thus, the study confirmed that the SNEDDS formulation can be used as a possible alternative to traditional oral formulations of ezetimibe to improve its bioavailability