Design and characterization of nanocrystal formulations containing ezetimibe

Abstract

Ezetimibe is a lipid-lowering compound that selectively inhibits the absorption of cholesterol and related phytosterols from the intestine. As ezetimibe is almost insoluble in water, its bioavailability is too low to be detected. Thus, the objective of this study was to improve the solubility and dissolution rate of ezetimibe by preparing drug nanocrystals utilizing ball milling, high speed homogenization techniques. Pluronic F127 was chosen as a surface modifier to stabilize the nanocrystal formulations. Nanocrystal formulations of ezetimibe were prepared by using ball milling and high speed homogenization techniques. Additionally, the physicochemical characteristics of ezetimibe and nanocrystal formulations were determined by Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), X-ray analysis and particle size analysis. Tablets were prepared containing ezetimibe nanocrystals formed by high speed homogenization (ultrasonic) and ball milling according to the results of particle size measurements and in vitro dissolution rates of the nanocrystal formulations. As a result of these experiments, it was found that the dissolution rate of the nanocrystal formulations increased and although tablet formulations which did not contain any solubilizing agent like sodium lauryl sulfate (SDS), the dissolution profile of these formulations were found similar to the commercial product. © 2011 Pharmaceutical Society of Japan.