title: Conformational polymorphism on imatinib mesylate: grinding effects.
abstract: 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.
authors: Departamento Física de la Materia Condensada, Gerencia de Investigación y Aplicaciones, Comisión Nacional de Energía Atómica, San Martín, Buenos Aires, Argentina.
authors: Damián
authors: D
authors: Grillo
authors: Griselda
authors: G
authors: Polla
authors: Daniel
authors: D
authors: Vega
mesh_terms: D001549:Benzamides; D003460:Crystallization; D019281:Dimerization; D000068877:Imatinib Mesylate; D008968:Molecular Conformation; D010879:Piperazines / Q000737:chemistry*; D033362:Powder Diffraction; D011743:Pyrimidines / Q000737:chemistry*
chemical_list: D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate