Studies on Orally Active Cephalosporin Esters. II. Chemical Stability of Pivaloyloxymethyl Esters in Phosphate Buffer Solution

Abstract

The degradation kinetics of pivaloyloxymethyl (POM) esters of cephalosporins in phosphate buffer solution (pH 6—8) were investigated. The degradation of the starting A3 cephalosporin ester proceeded mainly via isomerization to the A2ester and subsequent hydrolysis to the A2acid. Hydrolysis to the A3acid (the parent acid) was very slow. Analysis of the rate constants indicated that the isomerization rate k12was approximately equal to the apparent degradation rate of the A3ester kdeg, and slower than the hydrolysis rate of the A2ester k24. The isomerization process to the A2ester was found to be the rate-determining step in the degradation of cephalosporin esters. The substituent at the C-3 position of the cephalosporins affected the degradation kinetics. The degradation was accelerated by increase of pH, buffer concentration and added protein. © 1989, The Pharmaceutical Society of Japan. All rights reserved.