Use of in situ FT-Raman spectroscopy to study the kinetics of the transformation of carbamazepine polymorphs
O'Brien, L. E., Timmins, P., Williams, A. and York, P. (2004) Use of in situ FT-Raman spectroscopy to study the kinetics of the transformation of carbamazepine polymorphs. Journal of Pharmaceutical and Biomedical Analysis, 36 (2). pp. 335-340. ISSN 0731-7085
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To link to this item DOI: 10.1016/j.jpba.2004.06.024
The solid-state transformation of carbamazepine from form III to form I was examined by Fourier Transform Raman spectroscopy. Using a novel environmental chamber, the isothermal conversion was monitored in situ at 130◦C, 138◦C, 140◦C and 150◦C. The rate of transformation was monitored by taking the relative intensities of peaks arising from two C H bending modes; this approach minimised errors due to thermal artefacts and variations in power intensities or scattering efﬁciencies from the samples in which crystal habit changed from a characteristic prism morphology (form III) to whiskers (form I). The solid-state transformation at the different temperatures was ﬁtted to various solid-state kinetic models of which four gave good ﬁts, thus indicating the complexity of the process which is known to occur via a solid–gas–solid mechanism. Arrhenius plots from the kinetic models yielded activation energies from 344 kJ mol−1 to 368 kJ mol−1 for the transformation. The study demonstrates the value of a rapid in situ analysis of drug polymorphic type which can be of value for at-line in-process control.