Physicochemical characterization and decomposition kinetics of trandolapril

Abstract

The purpose of this work was to study the physicochemical properties of trandolapril, to perform a detailed kinetic study of its decomposition and also to evaluate its thermal stability in order to provide the essential tools to design a thermal destruction method for expired trandolapril-based drugs. Trandolapril was characterized with FTIR, XRPD and SEM and its thermal behaviour was studied with DSC and TGA in dry air and nitrogen flows. The decomposition process was also followed by Py-GC–MS, the activation energy was calculated with isoconversional methods and the reaction model was determined with model-fitting method. Trandolapril is stable until the onset of its melting (110°C) in both nitrogen and dry air environments. Thermal degradation of trandolapril can be described by two consecutive mechanisms of n-th order with activation energies 97.4 and 180.0kJ/mol respectively. Trandolapril reaches zero residual at 510 and 560°C in nitrogen and dry air flow respectively. The detailed analysis of decomposition mechanism allows the industry to design integrated thermal destruction processes for expired trandolapril-based drugs. The results of Py-GC–MS agree with the theoretical calculations of thermal analysis techniques, which highlights that the different techniques used in this work are complementary and equally important.