Kinetic studies of the degradation of an aminopenicillin antibiotic (amoxicillin trihydrate) in aqueous solution using heat conduction microcalorimetry

Abstract

Abstract Recent developments in isothermal microcalorimetry allow the direct determination of kinetic and thermodynamic parameters for slow reactions from studies conducted at appropriate temperatures and under designated environmental control. The degradation kinetics of amoxicillin trihydrate has been investigated as a function of pH (1–10) and temperature (303.15–318.15 K) at 0.5 M ionic strength using heat conduction microcalorimetry. Equations were developed incorporating calorimetric accessible data, rate constants and change in enthalpy, which showed that the degradation of amoxicillin trihydrate in aqueous solution followed pseudo-first-order kinetics under our experimental conditions. The enthalpy of degradation reaction was found to be exothermic in nature. The values of the rate constant k for individual steps were determined from the values of the overall rate constants at different pH. Energy of activation of overall reaction as a function of pH and for individual rate constants was determined. The log k-pH profiles indicated specific-acid and specific-base catalysis and there were inflection points near pH 3 and pH 7 corresponding to the pKa1 and pKa2 values. Quantitatively, there was good correlation between calorimetric determined half-life (t1/2) and the literature value in the acidic region determined by other methods at 310.15 K. The presence of a β-lactam ring and of an α-amino group in the C-6 side chain played a critical role in the degradation of amoxicillin trihydrate and the zwitterionic form of the drug was found to be more stable.