Polymorphism of carbamazepine

Although simple intensity correction techniques can be used to develop very adequate XRPD methods of quantitative analysis, the introduction of more sophisticated data acquisition and handling techniques can greatly improve the quality of the developed method. For instance, improvement of the powder pattern quality through the use of the Rietveld method has been used to evaluate mixtures of two anhydrous polymorphs of carbamazepine and the dihydrate solvatomorph [43]. The method of whole pattern analysis developed by Rietveld [44] has found widespread use in crystal structure refinement and in the quantitative analysis of complex mixtures. Using this approach, the detection of analyte species was possible even when their concentration was less than 1% in the sample matrix. It was reported that good quantitation of analytes could be obtained in complex mixtures even without the requirement of calibration curves. 

Behme, R.J. Brooke, D. Heat of fusion measurement of a low melting polymorph of carbamazepine that undergoes multiple-phase changes during differential scanning calorimetry analysis. J. Pharm. Sci. 1991, 80 (10), 986-990. 

Edwards, A.D. Shekunov, B.Y. Kordikowski, A. Forbes, R.T. York, P. Crystallization of pure anhydrous polymorphs of carbamazepine by solution enhanced dispersion with supercritical fluids (SEDS ). J. Pharm. Sci. 2001, 90 (8), 1115-1124. 

Behme ly and Brooke D. Heat of Fusion Measurement of a Low Melting Polymorph of Carbamazepine that Undergoes Multiple-Phase Changes During Differential Scanning Calorimetry Analysis./PAarro Sci 1991 80 986—990. 

Variable-temperature vibrational spectroscopy can be a powerful tool for the study of phase transitions and/or desolvation processes. The technique has been combined with factor analysis to deduce the three phase transitions and four conformational changes associated with pentaerythritol tetrastearate [129]. In this particular work, each thermal event was substantiated by analogous DSC studies. The dihydrates prepared from the two polymorphs of carbamazepine were also studied using variable-temperature techniques [130]. 

Figure 3.11 Views of the crystal packing of carbamazepine, form 3. This is the stable polymorph of carbamazepine at room temperature...

Many examples exist in the literature of studies using DSC as a method for predicting the presence of polymorphs of a compound [ 14]. A recent example is that of carbamazepine, a drug used in the treatment of epilepsy. It has been shown successfully using DSC that three distinct polymorphs of carbamazepine exist. These findings were backed up by results obtained from Fourier transform infrared (FTIR) and XRPD experiments [15]. However,... 

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