Co-crystals of ezetimibe: design, formulation and evaluation

Abstract

Crystallization is a very promising approach to design solid-state properties with desired physicochemical properties. The objective of the present research work was to design, formulate and evaluate Ezetimibe cocrystals. In the present study, Cocrystals of Biopharmaceutics Classification System (BCS) Class II drug, Ezetimibe using 3-pyridine carboxamide as coformer were prepared. 3-pyridine carboxamide was selected as suitable coformer from initial screening. Cocrystals of Ezetimibe with 3-pyridine carboxamide were obtained in 1:1 ratio by solution crystallization method. Hot stage microscopy indicated interaction among drug and coformer. Differential scanning calorimetry spectra of formulated cocrystals reflected shift in endotherm corresponding to melting point in comparison to Ezetimibe, coformer and physical mixture. Fourier transform infrared (FTIR) spectra indicated towards shifting in specific bands characteristic of Ezetimibe. X-Ray Powder Diffraction pattern pointed towards crystallinity and difference in 2θ values of characteristic peaks. The cocrystals showed faster dissolution rate in comparison to Ezetimibe and marketed sample. Pharmacodynamic investigation reveals that cocrystals reduced lipid levels in serum in comparison to pure drug. Pharmaceutical Cocrystals of Ezetimibe with 3-pyridine carboxamide represented a promising approach to improve bioavailability of Ezetimibe drug.