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Mechanistic in situ and ex situ studies of phase transformations in molecular co-crystals

Clout, Alexander E.; Buanz, Asma B.M.; Pang, Yuying; Tsui, Wing Mei; Yan, Dongpeng; Parkinson, Gary; Prior, Timothy J.; Bučar, Dejan Krešimir; Gaisford, Simon; Williams, Gareth R.

Authors

Alexander E. Clout

Asma B.M. Buanz

Yuying Pang

Wing Mei Tsui

Dongpeng Yan

Gary Parkinson

Dejan Krešimir Bučar

Simon Gaisford

Gareth R. Williams



Abstract

Co‐crystallisation is widely explored as a route to improve the physical properties of pharmaceutical active ingredients, but little is known about the fundamental mechanisms of the process. Herein, we apply a hyphenated differential scanning calorimetry—X‐ray diffraction technique to mimic the commercial hot melt extrusion process, and explore the heat‐induced synthesis of a series of new co‐crystals containing isonicotinamide. These comprise a 1:1 co‐crystal with 4‐hydroxybenzoic acid, 2:1 and 1:2 systems with 4‐hydroxyphenylacetic acid and a 1:1 crystal with 3,4‐dihydroxyphenylactic acid. The formation of co‐crystals during heating is complex mechanistically. In addition to co‐crystallisation, conversions between polymorphs of the co‐former starting materials and co‐crystal products are also observed. A subsequent study exploring the use of inkjet printing and milling to generate co‐crystals revealed that the synthetic approach has a major effect on the co‐crystal species and polymorphs produced.

Citation

Clout, A. E., Buanz, A. B., Pang, Y., Tsui, W. M., Yan, D., Parkinson, G., …Williams, G. R. (2020). Mechanistic in situ and ex situ studies of phase transformations in molecular co-crystals. Chemistry : a European journal, 26(64), 14645-14653. https://doi.org/10.1002/chem.202002267

Journal Article Type Article
Acceptance Date Jul 24, 2020
Online Publication Date Jul 24, 2020
Publication Date Nov 17, 2020
Deposit Date Dec 8, 2020
Publicly Available Date Dec 8, 2020
Journal Chemistry: a European journal
Print ISSN 0947-6539
Electronic ISSN 1521-3765
Publisher Wiley
Peer Reviewed Peer Reviewed
Volume 26
Issue 64
Pages 14645-14653
DOI https://doi.org/10.1002/chem.202002267
Keywords Differential scanning calorimetry; Hyphenated techniques; Pharmaceutical co-crystals; Synchrotron X-ray diffraction
Public URL https://hull-repository.worktribe.com/output/3547159
Publisher URL https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/chem.202002267

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Publisher Licence URL
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Copyright Statement
© 2020 The Authors. Published by Wiley-VCH GmbH. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited





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