RESUMO
OBJECTIVE: The investigation of benznidazole (BZN), excipients, and tablets aims to evaluate their thermal energy and tableting effects. They aim to understand better the molecular and pharmaceutical processing techniques of the formulation. SIGNIFICANCE: The Product Quality Review, part of Good Manufacturing Practices, is essential to highlight trends and identify product and process improvements. METHODS: A set of technique approaches, infrared spectroscopy, X-ray diffraction, and thermal analysis with isoconversional kinetic study, were applied in the protocol. RESULTS: X-ray experiments suggest talc and α-lactose monohydrate dehydration and conversion of ß-lactose to stable α-lactose upon tableting. The signal crystallization at 167 °C in the DSC curve confirmed this observation. A calorimetric study showed a decrease in the thermal stability of BZN tablets. Therefore, the temperature is a critical process parameter. The specific heat capacity (Cp) of BZN, measured by DSC, was 10.04 J/g at 25 °C and 9.06 J/g at 160 °C. Thermal decomposition required 78 kJ mol-1. Compared with the tablet (about 200 kJ mol-1), the necessary energy is two-fold lower, as observed in the kinetic study by non-isothermal TG experiment at 5; 7.5; 10; and 15 °C min-1. CONCLUSIONS: These results indicate the necessity of considering the thermal energy and tableting effects of BZN manufacturing, which contributes significantly to the molecular mechanistic understanding of this drug delivery system.
