Kinetic investigation and predictive model for the isothermal degradation time in two commercial acetylsalicylic acid-based pharmaceutical tablet formulations

Differential scanning calorimetry was used as a rapid screening technique to study the stability of acetylsalicylic acid (ASA), pure or contained in two commercially available pharmaceutical tablet formulations, denoted as PF1 and PF2, where ASA is present at a high nominal concentration, along with some of the most commonly used excipients (starch, cellulose, saccharin). The stability study was focused on the kinetic analysis of the thermal decomposition of ASA, which occurs in pure ASA as well in the two pharmaceutical tablet formulations, using two well-known multi-heating model-free kinetic methods: Kissinger and Ozawa–Flynn–Wall. A knowledge of the Arrhenius parameters related to this process (activation energy Ea, pre-exponential factor A, kinetic constant k) allows the half-life time values (extrapolated at 25 °C) to be calculated at fixed percentages of product degraded for pure ASA as well for both dosage forms considered. Finally, the novelty of this study is represented by the results of long-term isothermal measurements, consistent with short-term non-isothermal (accelerating) measurements, provided a reasonable predictive model to calculate the isothermal degradation times, thus demonstrating the reliability of extrapolated half-life times obtained in this study.

► Thermal behaviour of the formulations tested have been studied by differential scanning calorimetry. ► Stability was evaluated by Kissinger and Ozawa–Flynn–Wall methods applied to decomposition process. ► Long-term isothermal degradation kinetic data were compared with non-isothermal short-term ones. ► Good agreement between long- and short-term results provided a reliable predictive model.