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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.; Bu?ar, Dejan Krešimir; Gaisford, Simon; Williams, Gareth R.


Alexander E. Clout

Asma B.M. Buanz

Yuying Pang

Wing Mei Tsui

Dongpeng Yan

Gary Parkinson

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Dr Tim Prior
Senior Lecturer in Inorganic Chemistry

Dejan Krešimir Bu?ar

Simon Gaisford

Gareth R. Williams


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.


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.

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 Oct 27, 2022
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
Keywords Differential scanning calorimetry; Hyphenated techniques; Pharmaceutical co-crystals; Synchrotron X-ray diffraction
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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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