(684d) A Kinetic Study of Crystallization Process of Imatinib Mesylate with Polymorphic Transformation Phenomenon
For pharmaceutical crystallization design and process control, the kinetics of dissolution, nucleation and growth of crystals are significant parameters, especially for the system existing polymorphic transformation. In this study, the model compound Imatinib mesylate with the trade name âGleevec/Glivecâ was thoroughly explored in the aspects of characterization, solubility and polymorphic transformation, and evaluation of nucleation and growth rate. Two forms of Imatinib mesylate, Î± and Î², was characterized firstly by Powder X-ray Diffraction, Scanning Electron Microscopy and Differential Scanning Calorimetry. To study the relative stability of ð¼-form and Î²-form imatinib mesylate, the solubility measurement was performed in five solvents from 278.15 to 333.15 K at atmospheric pressure for the first time. Results indicate the Î²-form is more stable under the operating condition and the solubility order in selected solvents is methanol> ethanol>1-propanol>butanol>2-propanol. The solvent-mediated polymorphic transformation (SMPT) from ð¼-form to ð½-form was studied with Raman spectroscopy in-situ and Ultravioletâvisible spectroscopy off-line. It is found that the SMPT process from ð¼-form to ð½-form imatinib mesylate in methanol is controlled by nucleation and growth of ð½-form. At last, the experimental data of solubility and SMPT in methanol was used to determine the dissolution rate of ð¼-form and the nucleation and grow rate of ð½-form imatinib mesylate with the parameter estimation in g-crystal software.
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