Ion-exchange chromatography and membrane separation process for the recovery of potassium clavulanate from fermentation broth

Abstract

A separation process that consists of ion-exchange chromatography (IEC) and desalting electrodialysis (DSED) steps has been developed for the recovery and purification of potassium clavulanate (KCA) from fermentation broth. A strong anion exchanger, Amberlite IRA 400 resin, a potassium acetate solution as equilibrium buffer, and a potassium chloride (KCl) solution as elution buffer were used for the recovery of KCA in linear gradient elution (LGE) IEC. In order to determine optimal operating conditions, the effects of various operating parameters such as equilibrium buffer pH and concentration, elution buffer concentration, gradient length, and volumetric flow rate on KCA recovery and by-product removal were investigated using a simulated fermentation broth. In the subsequent step, DSED was carried out to remove KCl that existed in a large amount in the ion-exchanged solution. The effects of operation voltage and feed composition on the performance of DSED were investigated. Finally, IEC and DSED were applied in sequence to an ultrafiltered fermentation broth. Almost complete removal of KCl was possible although the KCA recovery was slightly lower than that with the simulated fermentation broth. Based on this observation it was concluded that IEC and DESD could be an effective process combination for the recovery of KCA from fermentation broth. A mathematical model based on the plate theory has been developed for LGE-IEC. The model prediction was in good agreement with the experimental data, suggesting that this model could be successfully applied to the prediction of elution behavior of clavulanate. To determine optimal operating conditions for LGE-IEC, iso-resolution concept was applied. Operating loci for various resolution levels and elution profiles at different gradient slopes and flow rates for a given resolution were calculated by using the proposed model. Based on these calculation results, optimal conditions could be identified for the maximization...