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

Autor: Roxana Lili Roque-Flores, Flavio Machado de Souza Carvalho, Juliana Ferreira de Oliveira, Jivaldo do Rosário Matos
Rok vydání: 2019
Předmět:
Zdroj: Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual)
Universidade de São Paulo (USP)
instacron:USP
ISSN: 1939-8042
1872-5120
Popis: 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.
Databáze: OpenAIRE
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