The Influence of Potassium Clavulanate on the Rate of Amoxicillin Sodium Degradation in Phosphate and Acetate Buffers in the Liquid State

Abstract

The stability of aqueous admixtures of amoxicillin sodium and potassium clavulanate was studied in the liquid state at selected pH values. Potassium clavulanate was found to catalyze the rate of degradation of amoxicillin sodium under the conditions of this study. In phosphate buffer (at pH 7.0) both amoxicillin sodium and potassium clavulanate showed first-order degradation when stored separately. However, when combined the rate of amoxicillin degradation increased and t90 values for amoxicillin decreased from 69.6 min for amoxicillin alone to 10.8 min for amoxicillin in the combination at 55°C. A kinetic model was developed that explained the catalytic behavior of potassium clavulanate and phosphate buffer. In acetate buffer the rate of degradation of amoxicillin sodium followed first-order kinetics, but the catalytic effect of clavulanate caused curvature in the rate plots at higher temperatures and clavulanate concentrations. This catalytic effect was less than that occurred in phosphate buffer (where the t90 value of amoxicillin decreased from 137.3 min for amoxicillin alone to 52.5 min for amoxicillin in combination at 55°C). First-order bi-exponential decay occurred with amoxicillin degradation, which explained this change in rate.