Dissolution rate enhancement of new co-crystals of ezetimibe with maleic acid and isonicotinamide

Abstract

Ezetimibe (EZT) is a selective cholesterol absorption inhibitor with poor aqueous solubility (0.012mg/ml 23 oC) and low oral bioavailability (about 35-65% for a once 10mg dose). The present study illustrates the preparation and characterization of two new co-crystals of ezetimibe using maleic acid and isonicotinamide as the coformers by solid grinding method. The co-crystal structures were characterized by X-ray powder diffraction (PXRD), differential scanning calorimetry (DSC), infrared spectroscopy (IR) techniques. Crystallinity and surface morphological characteristics of these prepared co-crystals were observed by scanning electron microscope (SEM). Dissolution rate tests demonstrated that both of the new co-crystals showed significant improvement in sodium lauryl sulfate -sodium acetate buffer solution (PH=4.5) at 15min and 20min. This study enriched the types of EZT co-crystals and identified that pharmaceutical co-crystal engineering technique play an important role in the dissolution rate enhancement of ezetimibe.