Kinetics of amoxicillin and clavulanate degradation alone and in combination in aqueous solution under frozen conditions

Abstract

Kinetics of the reactions of amoxicillin sodium and potassium clavulanate alone and in combination were investigated in the frozen state at selected pH values of 2.0, 4.6 and 7.0. Extrapolation of the rate constant values to the frozen state from the liquid state data indicated marked acceleration of the rates of amoxicillin and clavulanate degradation for the pH values investigated. The highest acceleration in rate recorded was 15.0-fold for clavulanate and the lowest value was 4.6-fold for amoxicillin at -7.3 degrees C in the hydrochloric acid system. The rate constant values obtained were interpreted in terms of the concentration model [Pincock, R.E., Kiovsky, T.E., 1966. Kinetics of reactions in frozen solution. J. Chem. Educ. 43, 358-360], phase-temperature relationship of the solutes, buffer catalysis, pH change and polymerization reactions. A kinetic model was deduced for the hydrochloric acid system providing adequate explanation of the experimental results. A large stabilizing effect of sodium chloride used for maintaining constant ionic strength (micro=0.5) was evident in this system. The shelf-life of amoxicillin was increased from 2.2 to 58.7h at -7.3 degrees C when sodium chloride was included in the hydrochloric acid system.