Influence of Surfactants and Polymers on the Kinetics of Hydrolytic Degradation of Cefuroxime Axetil

ABSTRACT The acid‐catalyzed hydrolysis of the prodrug Cefuroxime Axetil (CFA) were quantitatively investigated in both the aqueous media and micro‐heterogeneous surfactant media. The kinetics were studied in the presence of perchloric acid, which served as the proton source. The micelles of sodium dodecyl sulfate (SDS) and Triton X‐100 (TX100) were found to inhibit the rate of hydrolysis. In contrast, water‐soluble polymers, such as polyvinyl alcohol (PVA) and polyethylene glycol (PEG), accelerated the reaction rate at lower concentrations, producing a peak‐like plot of the rate constant versus polymer concentration. This inhibition is attributed to the partitioning (or solubilization) of the lipophilic CFA substrates into the less polar core of the micelles. This sequestration separates the CFA from the high concentration of the hydronium ion (H 3 O + ) in the bulk aqueous phase, thereby decreasing the local concentration of reactants at the reaction interface and reducing the effective rate constant. At low polymer concentrations, an acceleration of the hydrolysis rate was observed, leading to a peak‐like profile (rate maximum) in the plot of the observed pseudo‐first‐order rate constant versus the polymer concentration. This initial acceleration is may be due to a combination of electrostatic and non‐covalent interactions (e.g., hydrogen bonding) between the polymer segments and the reactants, effectively increasing the local concentrating of CFA and (H + ) ions in the vicinity of the polymer chain. The subsequent decrease in the rate constant values after the maximum is attributed to the formation of polymer‐micelle‐like aggregates that sterically hinder the reaction. The micellar rate constant values were treated using the pseudo‐phase model from which the binding constant (K s ) for CFA into the micellar pseudo‐phase and the micellar rate constant values (k m ) were determined through the iterative method.