CARBENICILLIN PRODRUGS - STABILITY KINETICS OF ALPHA-PHENYL AND ALPHA-INDANYL ESTERS IN AQUEOUS-SOLUTION

Both ester and β‐Iactam degradations of α‐esters of carbenicillin disodium, carbenicillin indanyl sodium, and carbenicillin phenyl sodium in aqueous solution at 35° and at 0.5 ionic strength were investigated. The reactions were followed by spectrophotometric assay, reversed‐phase high‐pressure liquid chromatography, and colorimetric assay. The degradation pathways were established, and the rate‐pH profiles for ester and β‐lactam cleavage reactions are given for pH 1‐11. Below pH 3, the β‐lactam degradation of the prodrugs proceeded exclusively. Above pH 7, the degradation was superseded by the ester hydrolysis to carbenicillin. β‐Lactams of both prodrugs are around three times more stable than carbenicillin disodium at pH 1, six times at pH 2, and 17 times at pH 3. The half‐lives for carbenicillin production were predicted to be 17 hr for carbenicillin indanyl sodium and 8.5 hr for carbenicillin phenyl sodium at pH 7.0 and 37°. Copyright © 1979 Wiley‐Liss, Inc., A Wiley Company