Jump to main content
Jump to site search

Issue 38, 2014
Previous Article Next Article

New cocrystals of ezetimibe with l-proline and imidazole

Author affiliations


The objectives of the study were to screen and prepare cocrystals of anti-cholesterol drug ezetimibe (EZT) with the aim of increasing its solubility and dissolution rate. Thermodynamic phase diagram based high throughput screening was performed using wet milling/grinding or solution crystallization methods. A large number of coformers were tested and the resulting solids were preliminarily characterized using X-ray powder diffraction (PXRD) and Raman spectroscopy. Potential cocrystals of EZT with L-proline and imidazole and a solvate formamide were identified in the screening experiments. The cocrystal hits were further characterized by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), solution Proton nuclear magnetic resonance spectroscopy (1H-NMR) and single crystal XRD. The dissolution properties and stability of cocrystals were determined. Single-crystal X-ray diffraction data were obtained for EZT, EZT-IMI cocrystal and formamide solvate of ezetimibe. All three systems were crystallized in non-centrosymmetric orthorhombic space group P212121 with Z = 4. Robust O–H⋯O, O–H⋯N, N–H⋯O and C–H⋯O hydrogen bonds played an important role in all these crystal structures. EZT-PRO cocrystal showed improved apparent solubility and solid state stability.

Graphical abstract: New cocrystals of ezetimibe with l-proline and imidazole

Back to tab navigation

Supplementary files

Publication details

The article was received on 02 Jun 2014, accepted on 27 Jul 2014 and first published on 18 Aug 2014

Article type: Paper
DOI: 10.1039/C4CE01127A
Author version
Download author version (PDF)
CrystEngComm, 2014,16, 8984-8993

  •   Request permissions

    New cocrystals of ezetimibe with L-proline and imidazole

    M. R. Shimpi, S. L. Childs, D. Boström and S. P. Velaga, CrystEngComm, 2014, 16, 8984
    DOI: 10.1039/C4CE01127A

Search articles by author