Application of ultrafiltration to improve the extraction of antibiotics

Abstract

The production of antibiotics typically consists of fermentation, removal of biomass, solvent extraction, and crystallization. Vacuum rotary filtration or other conventional filtration systems and microfiltration are used to remove the biomass, but the biomass removal step fails to remove macromolecules including polysaccharides and proteins which may act as emulsifiers causing emulsion in the subsequent solvent extraction process, and reducing the process efficiency and product quality. In this work, an attempt was made to remove these “emulsifiers” before solvent extraction using ultrafiltration (UF). Bench and pilot scale spiral wound membrane modules with the MWCO of 5, 20 and 50 kDa were tested to treat benzylpenicillin (Pen G) broth following microbe removal. The UF permeates were subsequently fed to solvent extraction (acidic extraction at pH 2.0). The experimental results showed that UF could significantly improve the extraction operation in terms of phase separation, elimination of the need for any de-emulsifier or wet agent, and increase extraction recovery and product quality. Similar improvements from UF were observed in the extractions of erythromycin and medmycin (alkaline extraction at pH 10.0 and 8.7, respectively). The experimental results show that UF is an alternative to the use of de-emulsifier or other wet agent to obtain good phase separation even by gravity without centrifugal extractor in solvent extractions of Pen G, erythromycin and medmycin. The mechanisms of the improvement of extraction were discussed based on the experimental results on characterizing the feed and permeate solutions of UF. And it was concluded that there existed bioemulsifiers in antibiotic fermentation broth and UF could successfully remove them and hence could improve the extraction operation.