Clavulanic acid (CA) is an industrially and clinically important β-lactamase inhibitor. It is co-administered with amoxicillin (Augmentin™) and used to fight a range of antibiotic resistant bacterial infections in over 135 million patients a year. CA is produced on a multi-tonne scale via fermentation of Streptomyces clavuligerus, followed by a multi-step extraction process. However, it is susceptible to hydrolysis in aqueous solutions over a wide range of conditions owing to its strained 4,5-bicyclic core (Figure 1, top). The effect of pH and temperature on CA degradation in the context of its complex industrial manufacture is presented in this study (Figure 1, bottom). Pseudo-first order kinetics were used to measure the rate of CA degradation in buffered potassium clavulanate solutions over the pH range 3-9 (Figure 1, bottom left). The experimental procedure was applied to samples taken from various parts of the manufacturing process stream to investigate the pH and temperature dependence of clavulanic acid degradation rate. CA was shown to be the most stable in the pH range 5-6; however, the optimal pH to minimise degradation was dependent on the CA environment. It was observed that CA degradation was accelerated at higher temperatures; the extent to which temperature affected degradation rate was found to be greater when the solution pH was outside of the optimal range (Figure 1, bottom right). These findings will enable a more cost-effective and sustainable manufacturing process.

pH and temperature effects on process-scale degradation of clavulanic acid

2019 Fall National Meeting

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.