Isolation of antibiotics from industrial fermentation broths using membrane technology

Evaluation of ultrafiltration performance for the purpose of isolation of clavulanic acid from fermentation broths was carried out using two tubular ceramic membranes with molecular weight cut-offs (MWCO) of 15 and 150 kDa and two flat sheet organic membranes with MWCO of 20 and 5 kDa in order to establish the sequence of operations needed to achieve a good phase separation when the permeates are subjected to solvent extraction. Ultrafiltration fluxes are higher for the 150 kDa membrane, but the quality of its permeate is not good enough for acceptable phase separation: so, for solid–liquid separation a further purification of its permeates using the 20 kDa membrane is required. The purification of the permeates of the membrane of 20 kDa using a membrane of 5 kDa was also investigated. This last operation did not brought any improvement to the process. Ultrafiltration experiments using either the membranes of 15 kDa or of 20 kDa directly for the solid liquid separation showed that a good performance is obtained for both membranes. High fluxes and high yields of antibiotic were obtained as well as a good phase separation when their permeates were subjected to solvent extraction.

Membranes with high MWCO, such as 150 kDa, display slightly higher permeation fluxes but their permeates originate a poor phase separation in the solvent extraction operation, due to the presence of proteins in the permeates. Qualitative analysis of these permeates show the presence of proteins with molecular weights in the range of 50–20 kDa. Membranes with about the same MWCO but different geometries and materials, such as the 20 and the 15 kDa membranes, behave quite similarly in which concerns permeation fluxes and phase separation in the solvent extraction step which is very easily achieved. For these two membranes, however, a distinction has to be made related with the recovery of the pure water permeation fluxes. While for the ceramic tubular membrane, one or sometimes two cycles of chemical cleaning are enough to restore the initial flux, for the organic membrane, mechanical cleaning has to be made prior to the chemical cleaning. This need of mechanical cleaning is clearly related with the geometry of the feed channels of the system, but organic membranes are also more difficult to regenerate as they need more cycles (about three or four) of chemical cleaning. Intermediate purification of the permeates is dispensable as we do not obtain significative improvement in either permeation fluxes, antibiotic yields or solvent extraction operation.