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Characterization and Kinetic Studies of the Thermal Degradation of Mebendazole Polymorphs A and C

  • Roxana Lili Roque-FloresEmail author
  • Juliana Ferreira de Oliveira
  • Flavio Machado de Souza Carvalho
  • Jivaldo do Rosário Matos
Original Article
  • 96 Downloads

Abstract

Purpose

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.

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.

Results

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.

Conclusions

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.

Keywords

Mebendazole Phase-transformation Physicochemical properties Thermal analysis Kinetic study Isothermal Non-isothermal 

Notes

Acknowledgments

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.

Funding Information

This study is supported by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) of Brazil.

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Departamento de Farmácia, Faculdade de Ciências FarmacêuticasUniversidade de São PauloSão PauloBrazil
  2. 2.Departamento de Química Fundamental, Instituto de QuímicaUniversidade de São PauloSão PauloBrazil
  3. 3.Departamento de Mineralogia e Petrologia, Instituto de GeociênciasUniversidade de São PauloSão PauloBrazil

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