Insights into the Thermal Degradation Kinetics of β-Lactam Antibiotics: A Comparative Study of Cefazolin, Ceftriaxone, and Meropenem

Background/Objectives: The thermal stability and degradation kinetics of β-lactam antibiotics are critical for understanding their behavior under processing and storage conditions. This study investigates the thermal decomposition of meropenem, ceftriaxone sodium, and cefazolin sodium in order to evaluate their kinetic parameters, assess the presence of the compensation effect, and determine isokinetic temperatures. Methods: Thermal analysis was performed using simultaneous TG/DTG/DSC measurements. Non-isothermal degradation experiments were conducted at four different heating rates. Kinetic parameters were evaluated using two isoconversional methods (Friedman and Flynn–Wall–Ozawa) and ASTM E698-based approach to obtain average activation energies. To determine the pre-exponential factor (A), the Coats–Redfern method was applied using multiple kinetic models. The resulting lnA—Ea pairs obtained from different models were used to construct lnA = f(Ea) correlations, enabling the evaluation of the compensation effect and calculation of isokinetic temperatures (Tiso). Results: All three β-lactam antibiotics exhibited consistent kinetic behavior across the applied models, with the F3 reaction model providing the best fit based on R2 values. A clear linear relationship between lnA and Ea was observed, confirming the presence of an enthalpy–entropy compensation effect. However, significant differences in isokinetic temperatures were obtained indicating variability in kinetic compensation behavior among the studied compounds. Conclusions: The thermal degradation of the investigated β-lactam antibiotics follows a consistent kinetic framework, supported by isoconversional and model-fitting approaches. Nevertheless, the absence of a unique isokinetic temperature suggests differences in transition-state stabilization and enthalpy–entropy balance, likely driven by structural variations among the compounds.