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.
Original language | English |
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Pages (from-to) | 6513-6520 |
Number of pages | 8 |
Journal | Crystal Growth and Design |
Volume | 18 |
Issue number | 11 |
DOIs | |
Publication status | Published - 7 Nov 2018 |
Externally published | Yes |
Keywords
- Calculations
- Chemical bonds
- Molecular dynamics
- Quantum theory
- Thermodynamic properties
- Thermodynamic stability
- Vibrational spectroscopy
- Vibrations (mechanical)
- Ab initio molecular dynamics
- Active pharmaceutical ingredients
- Inter-molecular forces
- IR and Raman spectra
- Molecular conformation
- Quantum mechanical simulations
- Solid-state density
- Spectral assignments
- Density functional theory