University of Limerick
Browse
Croker_2020_Enabling.pdf (2.3 MB)

Enabling cocrystallization of challenging systems: passing through a stable cocrystal solvate as a pathway to strenuous cocrystal forms

Download (2.3 MB)
journal contribution
posted on 2020-03-30, 14:38 authored by J.B. de Maere d'Aertrycke, R. Payen, L. Collard, K. Robeyns, Denise M. Croker, T. Leyssens
Caffeine and maleic acid can form various cocrystal forms, which is a potential route to avoiding hydration issues of caffeine. This particular system was intensively studied as it not only shows cocrystal polymorphism but also stoichiometrically diverse cocrystals with a 1:1 maleic acid: caffeine (MC) and a 1:2 maleic acid:caffeine (MC2) form already identified. A cocrystallization process for MC was already developed. However, a process leading to pure MC2 remained a challenge, as the stability zone of the MC2 suspension is very narrow in most solvents. In this paper, we propose an alternative crystallization pathway toward this crystal form, passing through a stable solvate. Indeed, we identified a novel cocrystal solvate of MC2 (MC2·MeCN) in acetonitrile at 9 °C. This cocrystal solvate is characterized by a large stability zone in the ternary phase diagram, and consequently, a crystallization process leading to this form can easily be devised. Upon filtration, and exposure to ambient atmosphere, MC2·MeCN is quickly desolvated leading to the pure MC2 cocrystal phase. In this contribution, we therefore show that cocrystal phases, which are seemingly strenuous to crystallize from solution, can be accessed by thinking out-of-the-box and using the properties of unexpected alternative phases.

History

Publication

Crystal Growth and Design;20 (3), pp. 2035-2043

Publisher

American Chemical Society

Note

peer-reviewed

Rights

© 2020 ACS This document is the Accepted Manuscript version of a Published Work that appeared in final form in Crystal Growth and Design, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see, https://doi.org/10.1021/acs.cgd.9b01691

Language

English

Usage metrics

    University of Limerick

    Categories

    No categories selected

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC