Derisking the Polymorph Landscape: The Complex Polymorphism of Mexiletine Hydrochlorid
| Autor: | James F. McCabe, Matthew T. Mulvee, Jonathan W. Steed, Stefanie Freitag-Pohl, Andrei S. Batsanov, David J. Berry, Katharina Edkins, Sten O. Nilsson Lill, Dmitry S. Yufit, Michael R. Probert, Jessica L. Andrews, David C. Apperley |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: | |
| Zdroj: | Andrews, J L, Nielsson Lill, S O, Freitag-Pohl, S, Apperley, D, Yufit, D S, Batsanov, A S, Mulvee, M T, Edkins, K, McCabe, J F, Berry, D J, Probert, M R & Steed, J W 2021, ' Derisking the Polymorph Landscape: The Complex Polymorphism of Mexiletine Hydrochlorid ', Crystal Growth & Design, vol. 21, no. 12, pp. 7150–7167 . https://doi.org/10.1021/acs.cgd.1c01009 Crystal Growth & Design, 2021, Vol.21(12), pp.7150-7167 [Peer Reviewed Journal] |
| Popis: | This work presents an updated solid-form discovery approach to the polymorphism of the antiarrhythmic drug mexiletine hydrochloride, in which experimental and computational techniques are combined to provide a rigorous characterization of the solid-form landscape of this compound. The resulting solid forms were characterized by powder and single-crystal X-ray diffraction, IR spectroscopy, differential scanning calorimetry, and 13C solid-state NMR. This approach reveals five solid-form types of mexiletine hydrochloride. Forms 1, 2, and 3 are mutually enantiotropically related anhydrous polymorphs, with Form 1 the room temperature stable form, Form 2 the high-temperature form, and Form 3 the thermodynamically stable polymorph between 148 and 167 °C. The final two forms termed Types A and B comprise two large families of isomorphous channel solvates, including a fourth nonsolvated form isostructural to the Type A solvates. We report 11 modifications of each solvate, in which a diverse range of solvents are included in the channels, without changing the fundamental structure of the drug framework. These experimental results go hand-in-hand with computational crystal structure prediction (using the AstraZeneca crystal structure prediction approach), which together suggest that it is unlikely further nonsolvated forms, at least with Z′ = 1, will be discovered under ambient conditions. |
| Databáze: | OpenAIRE |
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