Physicochemical characterization and pharmacological evaluation of ezetimibe-PVP K30 solid dispersions in hyperlipidemic rats

摘要

The aim of this study was to improve the physicochemical properties as well as therapeutic efficacy of ezetimibe (EZT), through preparation of the solid dispersion (SD). SDs were formulated using polyvinylpyrrolidone K30 (PVP) via solvent method. The physicochemical properties along with in vitro drug release patterns of the prepared SDs were examined. To estimate the therapeutic efficiency of prepared SDs, in vivo studies including measurement of serum lipid levels, liver index and histological analysis of the liver tissue in hyperlipidemic rats were performed. Differential scanning calorimetry (DSC) and powder X-ray diffractometery (PXRD) showed that the drug crystallinity was remarkably decreased during preparation process. Faster drug release pattern of SDs was proved by in vitro dissolution test. Administration the SD of EZT led to a significant decrease in serum total cholesterol (TC) and LDL-C level as well as liver index in hyperlipidemic rats (P<0.05) compared to the PM. Furthermore, histological analysis of the liver tissue confirmed the improved efficacy of the SDs on the liver steatosis. In the present study, we demonstrated that the SDs of EZT with improved physicochemical characteristics had favorable effects on liver steatosis, liver index and serum lipid levels in the high fat diet-induced hyperlipidemic rats. (C) 2015 Elsevier B.V. All rights reserved.