Carbamazepine polymorphism: A re-visitation using Raman imaging

Raman imaging methods have appeared in the last years as a powerf u l approach to monitoring the qualit y of pharmaceutical compounds. Because polymorphism occurs in many crystalline pharmaceutical compounds, it is essential to monitor polymorphic transformations induced by different external stimulus, such as temperature changes, to which those compounds may be submitted. Raman imaging with k-means cluster analysis (CA) is used here as an essential technique to investigate structural and chemical transformations occurring in carba-mazepine p-monoclinic (CBZ III) into carbamazepine triclinic (CBZ I) when submitted to temperatures near the melting point of CBZ III (178 ?degrees C) and CBZ I (193 ?degrees C).CBZ II I commercial powder and laboratorial prepared CBZ I were analyzed by differential scanning calo-rimetry, powder X-ray diffraction and Raman spectroscopy with variable temperature. After thermal treatment, the resultant CBZ powder was evaluated by Raman imaging, in which a l l imaging data was analyzed using CA . Raman imaging allowed the identification of different polymorphs of CBZ (CBZ I I I and CBZ I ) and iminostilbene (IMS), a degradation product of CBZ, in the treated samples, depending on the heatin g treatment method.

Automated summary

Raman imaging with cluster analysis was used to investigate structural and chemical transformations in carbamazepine polymorphs induced by temperature changes, allowing the identification of different polymorphs and degradation products.