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.

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: 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
• 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