Opening Pandora’s Box: Chirality, Polymorphism, and Stoichiometric Diversity in Flurbiprofen/Proline Cocrystals
(2018) Crystal Growth & Design — Vol. 18, n° 2, p. 954-961 (2018)
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- Proline has been widely used for various cocrystallization applications, including pharmaceutical cocrystals. Combining enantiopure and racemic flurbiprofen and proline, we discovered 18 new crystal structures. Liquid-assisted grinding proved highly efficient to explore all the variety of crystal forms. A unique combination of stateof-the-art characterization techniques, comprising variable temperature in situ X-ray diffraction and in situ ball-milling, along with other physicochemical methods and density functional theory calculations, was indispensable for identifying all the phases. Analyzing the results of in situ ball-milling, we established a stepwise mechanism for the formation of several 1:1 cocrystals via an intermediate 2:1 phase. The nature of the solvent in liquidassisted grinding was found to significantly affect the reaction rate and, in some cases, the reaction pathway.
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Citations
Tumanova, N., Tumanov, N., Robeyns, K., Fischer, F., Fusaro, L., Morelle, F., Ban, V., Hautier, G., Filinchuk, Y., Wouters, J., Leyssens, T., & Emmerling, F. (2018). Opening Pandora’s Box: Chirality, Polymorphism, and Stoichiometric Diversity in Flurbiprofen/Proline Cocrystals. Crystal Growth & Design, 18(2), 954-961. https://doi.org/10.1021/acs.cgd.7b01436 (Original work published 2018)