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Exploring the potential of multinuclear solid‐state 1H, 13C, and 35Cl magnetic resonance to characterize static and dynamic disorder in pharmaceutical hydrochlorides
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Szell, Patrick M. J., Rehman, Zainab, Tatman, Ben P., Hughes, Leslie P., Blade, Helen and Brown, Steven P. (2023) Exploring the potential of multinuclear solid‐state 1H, 13C, and 35Cl magnetic resonance to characterize static and dynamic disorder in pharmaceutical hydrochlorides. ChemPhysChem, 24 (3). e202200558. doi:10.1002/cphc.202200558 ISSN 1439-4235.
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WRAP-multinuclear-solid-state-1H-13C-35Cl-static-dynamic-disorder-pharmaceutical-hydrochlorides-Brown-2022.pdf - Accepted Version Embargoed item. Restricted access to Repository staff only - Requires a PDF viewer. Download (3997Kb) |
Official URL: http://doi.org/10.1002/cphc.202200558
Abstract
Crystallographic disorder, whether static or dynamic, can be detrimental to the physical and chemical stability, ease of crystallization and dissolution rate of an active pharmaceutical ingredient. Disorder can result in a loss of manufacturing control leading to batch to batch variability and can lengthen the process of structural characterization. The range of NMR active nuclei makes solid-state NMR a unique technique for gaining nucleus-specific information about crystallographic disorder. Here, we explore the use of high-field 35Cl solid-state NMR at 23.5 T to characterize both static and dynamic crystallographic disorder: Specifically, dynamic disorder occurring in duloxetine hydrochloride (1), static disorder in promethazine hydrochloride (2), and trifluoperazine dihydrochloride (3). In all structures, the presence of crystallographic disorder was confirmed by 13C cross-polarization magic-angle spinning (CPMAS) NMR and supported by GIPAW-DFT calculations, and in the case of 3, 1H MAS NMR provided additional confirmation. Applying 35Cl solid-state NMR to these compounds, we show that higher magnetic fields are beneficial for resolving the crystallographic disorder in 1 and 3, while broad spectral features were observed in 2 even at higher fields. Combining the data obtained from 1H, 13C, and 35Cl NMR, we show that 3 exhibits a unique case of disorder involving the +N-H hydrogen positions of the piperazinium ring, driving the chloride anions to occupy 3 distinct sites.
Item Type: | Journal Article | |||||||||||||||
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Subjects: | Q Science > QC Physics Q Science > QD Chemistry R Medicine > RS Pharmacy and materia medica |
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Divisions: | Faculty of Science, Engineering and Medicine > Science > Physics | |||||||||||||||
Library of Congress Subject Headings (LCSH): | Crystallography , Nuclear magnetic resonance spectroscopy, Pharmaceutical chemistry, X-ray crystallography, Organic compounds , Density functionals | |||||||||||||||
Journal or Publication Title: | ChemPhysChem | |||||||||||||||
Publisher: | Wiley | |||||||||||||||
ISSN: | 1439-4235 | |||||||||||||||
Official Date: | 1 February 2023 | |||||||||||||||
Dates: |
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Volume: | 24 | |||||||||||||||
Number: | 3 | |||||||||||||||
Article Number: | e202200558 | |||||||||||||||
DOI: | 10.1002/cphc.202200558 | |||||||||||||||
Status: | Peer Reviewed | |||||||||||||||
Publication Status: | Published | |||||||||||||||
Reuse Statement (publisher, data, author rights): | This is the peer reviewed version of the following article: Szell, P.M., Rehman, Z., Tatman, B.P., Hughes, L.P., Blade, H. and Brown, S.P. (2022), Exploring the Potential of Multinuclear Solid-state 1H, 13C, and 35Cl Magnetic Resonance to Characterize Static and Dynamic Disorder in Pharmaceutical hydrochlorides. ChemPhysChem. Accepted Author Manuscript. https://doi.org/10.1002/cphc.202200558, which has been published in final form at https://doi.org/10.1002/cphc.202200558. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited. | |||||||||||||||
Access rights to Published version: | Open Access (Creative Commons) | |||||||||||||||
Copyright Holders: | © 2022 Wiley-VCH GmbH | |||||||||||||||
Date of first compliant deposit: | 6 October 2022 | |||||||||||||||
Date of first compliant Open Access: | 15 June 2023 | |||||||||||||||
RIOXX Funder/Project Grant: |
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