title: Use of in situ FT-Raman spectroscopy to study the kinetics of the transformation of carbamazepine polymorphs.
abstract: 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 degrees C, 138 degrees C, 140 degrees C and 150 degrees C. The rate of transformation was monitored by taking the relative intensities of peaks arising from two CH 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.
authors.affiliation: Drug Delivery Group, School of Pharmacy, University of Bradford, Bradford, West Yorkshire BD71DP, UK.
authors.forename: Laura E
authors.initials: LE
authors.lastname: O'Brien
authors.forename: Peter
authors.initials: P
authors.lastname: Timmins
authors.forename: Adrian C
authors.initials: AC
authors.lastname: Williams
authors.forename: Peter
authors.initials: P
authors.lastname: York
mesh_terms: D000927:Anticonvulsants / Q000737:chemistry*; D002220:Carbamazepine / Q000737:chemistry*; D006358:Hot Temperature; D007536:Isomerism; D007700:Kinetics; D013059:Spectrum Analysis, Raman; D013696:Temperature
chemical_list: D000927:Anticonvulsants; D002220:Carbamazepine