Mechanistic In Situ and Ex Situ Studies of Phase Transformations in Molecular Co-Crystals.

Autor: Clout AE; UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London, WC1N 1AX, UK., Buanz ABM; UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London, WC1N 1AX, UK., Pang Y; UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London, WC1N 1AX, UK., Tsui WM; UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London, WC1N 1AX, UK., Yan D; College of Chemistry, Beijing Normal University, Beijing, 100875, China., Parkinson G; UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London, WC1N 1AX, UK., Prior TJ; Department of Chemistry and Biochemistry, University of Hull, Hull, HU6 7RX, UK., Bučar DK; Department of Chemistry, University College London, 20 Gordon Street, London, WC1H 0AJ, UK., Gaisford S; UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London, WC1N 1AX, UK., Williams GR; UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London, WC1N 1AX, UK.
Jazyk: angličtina
Zdroj: Chemistry (Weinheim an der Bergstrasse, Germany) [Chemistry] 2020 Nov 17; Vol. 26 (64), pp. 14645-14653. Date of Electronic Publication: 2020 Oct 07.
DOI: 10.1002/chem.202002267
Abstrakt: 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.
(© 2020 The Authors. Published by Wiley-VCH GmbH.)
Databáze: MEDLINE
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