Improvement in physicochemical properties of ezetimibe using a crystal engineering technique

In an attempt to improve the physicochemical properties of poorly aqueous soluble ezetimibe, its pharmaceutical co-crystals were successfully engineered with different crystal forming agents; benzoic acid and salicylic acid in equimolar ratios by solution crystallization technique. The physicochemical properties of pure ezetimibe and corresponding co-crystals were accessed in terms of phase solubility studies, melting point, flowability, drug content uniformity, saturation solubility and dissolution studies. Fourier transformation infrared spectroscopy (FTIR), X-ray powder diffractometry (XRPD) and scanning electron microscopy (SEM) techniques were employed to investigate the hydrogen bonding interaction, crystallinity and surface morphological characteristics of prepared co-crystals respectively. The results indicated a marked improvement in flow properties and saturation solubility of co-crystals (p < 0.001). Further, in case of dissolution experiments, both the co-crystals showed a significant enhancement (DE5 and DE20, p < 0.001) in the dissolution profiles as compared to pure ezetimibe. It could be concluded that substantial manipulation of physicochemical properties of ezetimibe could be possible with benzoic acid and salicylic acid using crystal engineering technique.

In order to improve the physicochemical properties of poorly aqueous soluble ezetimibe, its pharmaceutical co-crystals were successfully engineered with benzoic acid and salicylic acid by solution crystallization technique. Physicochemical studies revealed a significant improvement in solubility, dissolution and micromeritic properties of ezetimibe from the co-crystals. In all aspects, salicylic acid served to be a choice of coformer for ezetimibe co-crystallization.Figure optionsDownload as PowerPoint slideHighlights
► We report crystal engineering of ezetimibe with benzoic and salicylic acids.
► We access both physicochemical and micromeritic properties of co-crystals.
► Characterization by FTIR, XRPD and SEM reveals formation of co-crystals.
► Co-crystallization improves overall physicochemical performance of ezetimibe.
► In all aspects, salicylic acid offers superiority over benzoic acid as a coformer.