Nanofiltration of a clarified fermentation broth

Membrane technology has a growing role in downstream processing of biopharmaceuticals showing greater performances than the traditional processes. Concerning the use of membrane technology for the isolation of clavulanic acid from fermentation broths, the major drawback is the severe flux decline observed during concentration by nanofiltration (NF) of the clarified broth. This work addresses the study of the NF, aiming the achievement of high fluxes and high clavulanic acid rejections. A suitable NF membrane is chosen and the main causes of flux decline are searched. The tested membranes (NFT50, Desal DL and Desal DK) were characterized, evidencing significant differences concerning their molecular weight cut-off (MWCO), hydraulic permeability, roughness (atomic force microscopy measurements) and rejection to clavulanic acid. However, for high volumetric concentrations of clarified broth, their fluxes were identical. Taking into account the average permeation fluxes and clavulanic acid retention, the membrane Desal DK was considered the most appropriate for carrying the clavulanic acid concentration. Throughout experiments with model solutions of increasing complexity, glucose and clavulanic acid were identified as the major contributors to flux decline due to concentration polarization together with enhanced osmotic pressures. Considering these mechanisms, a simplified approach was used aiming the modelling of the observed flux decline of both model and real solutions.