Crystal structures of polymorphs α and β 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 α and β 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 π-π interactions. Connections between dimers are provided by mesylate ions to determine chains of dimers. Neighboring chains are linked by very weak interactions: C-H···π interactions in form α and π-π interactions in form β. At room temperature, thermal disorder was observed in the mesylate ion in form α, which could be removed at low temperatures (-123°C). Form β 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 β 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.
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