Solid State Stability and Kinetics of Degradation for Candesartan—Pure Compound and Pharmaceutical Formulation

The aim of this work was to assess the impact of an excipient in a pharmaceutical formulation containing candesartan cilexetil over the decomposition of the active pharmaceutical ingredient and to comparatively investigate the kinetics of degradation during thermolysis in an oxidative atmosphere under controlled thermal stress. To achieve this, the samples were chosen as follows: pure candesartan cilexetil and a commercial tablet of 32 mg strength. As a first investigational tool, Universal attenuated total reflection Fourier transform infrared (UATR-FTIR) spectroscopy was chosen in order to confirm the purity and identity of the samples, as well as to check if any interactions took place in the tablet between candesartan cilexetil and excipients under ambient conditions. Later on, samples were investigated by thermal analysis, and the elucidation of the decomposition mechanism was achieved solely after performing an in-depth kinetic study, namely the use of the modified non-parametric kinetics (NPK) method, since other kinetic methods (American Society for Testing and Materials—ASTM E698, Friedman and Flynn–Wall–Ozawa) led to inadvertencies. The NPK method suggested that candesartan cilexetil and the tablet were degraded by the contribution of two steps, the main being represented by chemical degradation and the secondary being a physical transformation. The excipients chosen in the formulation seemed to have a stabilizing effect on the decomposition of the candesartan cilexetil that was incorporated into the tablet, relative to pure active pharmaceutical ingredient (API), since the apparent activation energy for the decomposition of the tablet was 192.5 kJ/mol, in comparison to 154.5 kJ/mol for the pure API.

Non-parametric kinetic analysis of thermogravimetric data for the thermal degradation of poly(tetrafluorethylene)

Thermal degradation of Teflon was investigated by thermoanalytical methods (TG and DTA). In the kinetic analysis of the experimental data, the NPK method proves to be a valuable tool, allowing for some new kinetic aspects of the degradation process to be obtained. Analysis of the computed isothermal and isoconversional vectors provided some insight into the reaction kinetics. Two different initiation pathways were suggested to control the global degradation kinetics, their relative contribution being temperature-dependant