Opening Pandora’s Box: Chirality, Polymorphism, and Stoichiometric Diversity in Flurbiprofen/Proline Cocrystals

Natalia Tumanova, Nikolay Tumanov, Koen Robeyns, Franziska Fischer, Luca Fusaro, Fabrice Morelle, Voraksmy Ban, Geoffroy Hautier, Yaroslav Filinchuk, Johan Wouters, Tom Leyssens, Franziska Emmerling

Résultats de recherche: Contribution à un journal/une revueArticleRevue par des pairs

Résumé

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 state-of-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 liquid-assisted grinding was found to significantly affect the reaction rate and, in some cases, the reaction pathway.
langue originaleAnglais
Pages (de - à)954-961
Nombre de pages8
journalCrystal Growth & Design
Volume18
Numéro de publication2
Les DOIs
Etat de la publicationPublié - 4 janv. 2018

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