Imatinib mesylate exhibits many polymorphic forms and most stable and commercialized polymorphs are α and β forms. Molecules in α and β polymorphic forms exhibit significant conformational differences due to their different intra- and intermolecular interactions, which stabilize their molecular conformations and affect their physicochemical properties such as bulk density, melting point, solubility, stability and process-ability. The manufacturing process of a drug tablet included granulation, compression, coating and drying may cause polymorphic conversions. Therefore, polymorphic content of the drug substance should be controlled during quality control and stability testing. Attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy, Differential Scanning Calorimetry (DSC) and powder X-ray diffraction (PXRD) methods were evaluated for determination of the polymorphic content of the drug substance and drug product. PXRD was the most accurate technique over the other two and selected as a preferred method and is used as validation method. In the present study, quantification PXRD and DSC methods have been developed to determine the amount of β-polymorphic form in α polymorph of imatinib mesylate tablets 400 mg and 100 mg. Mixtures with different ratios of α and β forms were scanned using X-ray diffractometer with a time per step(s) 1000 over an angular range of 19.9–21.0° 2θ and the peak heights for characteristic peak of β form at 20.5±0.2° 2θ diffraction angle were used to generate a calibration curve. The detection limit of β polymorph in α form imatinib mesylate tablets was found as 0.5% and the linear regression analysis data for the calibration plots showed good linear relationship with correlation coefficient of 0.9999 with respect to relative peak height in the concentration range of 1–30 wt% β form containing tablet mixtures. The obtained results at each stage of the validation study proved that the method is specific, repeatable, precise and accurate and could be used for determination of β polymorph content in tablets produced by using α polymorph of imatinib mesylate. The developed PXRD quantification method was used to monitor the polymorphic purity of α form drug substance and corresponding drug products during the quality control analyses and stability studies.
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