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Supramolecular synthonic portions in heat-treated indomethacin-carbamazepine mixture: a singular value decomposition
Wataru Kuwashima1, Kanji Hasegawa1, Chihiro Tsunoda1
1Faculty of Pharmaceutical Sciences, Tokyo University of Science, 6-3-1 Niijuku, Katsushika, Tokyo 125-8585, Japan.
Abstract:
Fourier-transform infrared spectra were measured for KBr tablets containing carbamazepine (CBZ), indomethacin (IMC) crystals, and their mixtures preheated at various temperatures. Singular value decomposition (SVD) of the differential spectra distinguished the average components, experimental-condition-dependent contributions, and non-contributing components (noise). Using the experimentally conditionally dependent contributions divided by the average components, simultaneous and comprehensive spectral transitions were identified, rather than focusing on specific signals. This indicates that SVD effectively detects the details of structural changes, including spectral peak shifts due to hydrogen bonding relaxation and molecular rearrangements. Consequently, the phase transition temperatures of CBZ and IMC were detected as 423 K (Form-III to Form-I transformation of CBZ) and 451 K (melting of the γ-form of IMC), respectively. CBZ exhibited spectral changes at 3464, 1676, 1381, and 763 cm-1, whereas IMC exhibited few shifts. CBZ/IMC mixture exhibited a phase-transition temperature of 394 K. The SVD selectively extracted spectral changes at 3465, 1690, 1385, 1306, and 1237 cm-1, highlighting the hydrogen bonding interactions between amide of CBZ and carboxylic acid of IMC as supramolecular synthons. These findings highlight the utility of advanced spectral analysis techniques such as SVD in the study of crystalline pharmaceutical substances.
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