Revisiting the Thermodynamic Stability of Indomethacin Polymorphs with Low-Frequency Vibrational Spectroscopy and Quantum Mechanical Simulations
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Publication Date
2018Journal Title
Crystal Growth and Design
ISSN
1528-7483
Publisher
American Chemical Society (ACS)
Volume
18
Issue
11
Pages
6513-6520
Type
Article
Metadata
Show full item recordCitation
Ruggiero, M., Sutton, J., Fraser-Miller, S., Zaczek, A., Korter, T., Gordon, K., & Zeitler, J. (2018). Revisiting the Thermodynamic Stability of Indomethacin Polymorphs with Low-Frequency Vibrational Spectroscopy and Quantum Mechanical Simulations. Crystal Growth and Design, 18 (11), 6513-6520. https://doi.org/10.1021/acs.cgd.8b00623
Abstract
The two major polymorphs of the active pharmaceutical ingredient indomethacin were studied using a combination of experimental low-frequency vibrational spectroscopies, theoretical solid-state density functional theory and ab initio molecular dynamics calculations. The results enable a complete spectral assignment of the low-frequency IR and Raman spectra, and yield new insight into the energetic and dynamical factors present within the solids to be understood. Ultimately, these results are used to rationalize the thermodynamic properties of the two crystals, which result in a contradiction to the long-held belief that the γ-form is the more stable polymorph at ambient conditions due to its predominant abundance. Overall, the study highlights the combined role that molecular conformation, bulk packing arrangement, and intermolecular forces have on the ultimate properties of pharmaceutical crystals, and the need for detailed analyses into all of these effects in order to predict the properties of materials.
Sponsorship
EPSRC (1198)
Identifiers
External DOI: https://doi.org/10.1021/acs.cgd.8b00623
This record's URL: https://www.repository.cam.ac.uk/handle/1810/286318
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Licence:
http://www.rioxx.net/licenses/all-rights-reserved
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