Conformational polymorphism on imatinib mesylate: Grinding effects

Crystal structures of polymorphs a and beta of imatinib mesylate were obtained. Thermal behavior and grinding effects were studied by X-ray powder diffraction and differential scanning calorimetry techniques. Molecules in forms a and beta exhibit significant conformational differences due to dissimilar intramolecular interactions, which stabilize their molecular conformations. In spite of that, both crystal structures present a dimer-chain arrangement. Dimers are mainly determined by hydrogen bonding interactions and some weak pi-pi pp interactions. Connections between dimers are provided by mesylate ions to determine chains of dimers. Neighboring chains are linked by very weak interactions: C-H center dot center dot center dot p interactions in form a and pi-pi interactions in form beta. At room temperature, thermal disorder was observed in the mesylate ion in form a, which could be removed at low temperatures (-123 degrees C). Form beta was found to be the more stable form at room temperature. Both polymorphs exhibit a tendency to generate amorphous material by grinding, which can be converted to a crystalline phase by either temperature or aging. When amorphous crystallization is kinetically studied at room temperature, form beta is obtained after a week. Conversely, when the crystallization is activated by temperature, the final obtained crystal form depends on the starting material, proving the importance of seeding. (C) 2011 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:541551, 2012