Revisiting the Thermodynamic Stability of Indomethacin Polymorphs with Low-Frequency Vibrational Spectroscopy and Quantum Mechanical Simulations
| Autor: | Timothy M. Korter, Joshua J. Sutton, J. Axel Zeitler, Sara J. Fraser-Miller, Michael T. Ruggiero, Keith C. Gordon, Adam J. Zaczek |
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| Přispěvatelé: | Ruggiero, MT [0000-0003-1848-2565], Korter, TM [0000-0002-0398-5680], Zeitler, JA [0000-0002-4958-0582], Apollo - University of Cambridge Repository |
| Rok vydání: | 2018 |
| Předmět: |
Materials science
34 Chemical Sciences Intermolecular force Infrared spectroscopy Bioengineering 02 engineering and technology General Chemistry 010402 general chemistry 021001 nanoscience & nanotechnology Condensed Matter Physics 01 natural sciences 0104 chemical sciences 3407 Theoretical and Computational Chemistry symbols.namesake Chemical physics Yield (chemistry) 3406 Physical Chemistry symbols General Materials Science Density functional theory Chemical stability 0210 nano-technology Raman spectroscopy Material properties Quantum |
| DOI: | 10.26434/chemrxiv.6155150.v1 |
| Popis: | 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 \textit{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 $\gamma$-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. |
| Databáze: | OpenAIRE |
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