Clavulanic acid decomposition is catalyzed by the compound itself and by its decomposition products.
The decomposition kinetics of the beta-lactamase inhibitor clavulanic acid (CA) was investigated for CA concentrations between 2.5 and 20 g L(-1), which is assumed to represent a characteristic range for an industrial CA production process. For each initial concentration, first order kinetics plots could be obtained, however the kinetic constant increased from 3.8 x 10(-3) to 8.6 x 10(-3) h(-1) with increasing initial CA concentration, indicating that CA accelerates its own decomposition by general acid-base catalysis. Furthermore, the kinetic constant remained approximately constant during the reaction, suggesting that also the decomposition products of CA had to show similar catalytic activity. This was confirmed experimentally by increased CA decomposition rates when CA degradation products were added to the reaction. A kinetic model is proposed, which is able to reliably predict the observed pseudo first order rate constants. The presented results should be considered in any process where highly concentrated CA solutions are employed, for example, during final downstream processing or in industrial fermentations.
Brethauer
Simone
S
ETH Zurich, Bioprocess Laboratory, Institute of Process Engineering, Universitaetsstrasse 6, 8092 Zurich, Switzerland.
Held
Martin
M
Panke
Sven
S
D002384:Catalysis; D019818:Clavulanic Acid / Q000493:pharmacokinetics*; D004791:Enzyme Inhibitors / Q000493:pharmacokinetics*; D008962:Models, Theoretical; D065093:beta-Lactamase Inhibitors
D004791:Enzyme Inhibitors; D065093:beta-Lactamase Inhibitors; D019818:Clavulanic Acid