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Time-Resolved X-ray Phase-Contrast Imaging (XPCI) of Nucleation and Crystal Growth in the Anti-Solvent Crystallization of Lovastatin

submitted on 03.09.2020, 08:18 and posted on 03.09.2020, 13:03 by Gunjan Das, Anuradha Pallipurath, Joanna Leng, Kazimir Wanelik, John McGinty, Russell Miller, Thokozile Kathyola, Sin-Yuen Chang, Laila H. Al-Madhagi, Shashidhara Marathae, Christoph Rau, Jan Sefcik, Sven L.M. Schroeder

X-ray phase contrast imaging (XPCI) of anti-solvent crystallization of lovastatin from an acetone/water solution was carried out in a concentric flow mixing device, using water as the anti-solvent. Spinodal decomposition of the solution is observed to give rise to ‘oiled out’ phases that undergo heterogeneous nucleation at the interface with the flowing solution. Heterogeneous nucleation is also observed on the walls of the reactor walls in the form of what appears to be Stranski–Krastanov growth of plate-like crystals. XPCI together with Eulerian video magnification forms a powerful tool for the spatio-temporal analysis, revealing mechanistic details of a non-equilibrium process such as anti-solvent crystallization.


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Engineering and Physical Sciences Research Council

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University of Leeds



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Declaration of Conflict of Interest

The authors declare no conflict of intrest

Version Notes

Version 1 along with three videos, visualising stage 1 -3 of image analysis showing the appearance of new features.