Characterization and Kinetic Studies of the Thermal Degradation of Mebendazole Polymorphs A and C
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Mebendazole is an anthelmintic drug of low solubility, which exhibits three polymorphic forms (A, B, and C) with different thermodynamic stability (A > C > B). Form C is the most appropriate for pharmaceutical development due to its adequate bioavailability and lower toxicity. This form is stable between room temperature ± 180 °C. The aim of this work was to characterize and study the thermal degradation kinetics of Mebendazole polymorphs A and C by isothermal and non-isothermal (Ozawa method) thermogravimetric methods.
Thermogravimetry (TG), differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), Fourier-transform infrared spectroscopy (FTIR), and elementary analysis (EA) were used to identify Mebendazole polymorphs A and C. Isothermal and non-isothermal thermogravimetric methods were used to study the thermal degradation kinetics of Mebendazole polymorphs.
The results showed that form C converts to the polymorphic form A after heating at 200 °C, exhibiting both exothermic and endothermic events before the first mass loss. Subsequent to this transformation, CO2 was released and the formation of a solid product occurred, which was characterized by EA and FTIR. These results suggested the presence of a Mebendazole impurity. The degradation kinetics studies of polymorphs A and C obtained by both methods indicated activation energy (Ea) values greater for polymorph C.
In fact, part of the energy provided to the polymorph C was used for the transformation to polymorph A, which explains its greater thermal stability. This indicates that polymorph C is very stable under ambient conditions, but at high temperatures (above 180 °C) the stability of polymorph A predominates.
KeywordsMebendazole Phase-transformation Physicochemical properties Thermal analysis Kinetic study Isothermal Non-isothermal
The authors thank Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) of Brazil for financial support. Roxana L. Roque-Flores thanks Dr. Zoraida López Murgueytio for helpful discussions.
This study is supported by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) of Brazil.
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