Journal of Membrane Science 347 (2010) 17–25 Contents lists available at ScienceDirect Journal of Membrane Science journal homepage: www.elsevier.com/locate/memsci A novel continuous re-extraction procedure of penicillin G by a micro-extractor based on ceramic membrane Yong Wu a,b , Wangliang Li b,c , Hongshuai Gao a,b , Qiang Li b,c , Yuguang Li a,b , Kang Wang a,b , Iram Mahmood a,b , Huizhou Liu a,∗ a Key Laboratory of Green Process and Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Zhongguancun, Bei’er tiao No. 1, Haidian District, Beijing 100190, China b Graduate University of Chinese Academy of Sciences, Beijing 100049, China c National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China article info Article history: Received 19 May 2009 Received in revised form 28 August 2009 Accepted 1 October 2009 Available online 9 October 2009 Keywords: Penicillin G Micro-extraction Liquid droplets Re-extraction efficiency Degradation Modeling abstract A ceramic membrane micro-extractor (CME), employed for continuous re-extraction of penicillin G (PEN G), was studied systematically. The droplet size was investigated in the re-extraction process. Re-extraction efficiency (RE) and degradation rate of PEN G were extensively examined by superficial Reynolds number (Re h ), phase ratio (R), initial PEN G concentration and membrane pore size. To fur- ther understand and quantitatively analyze the re-extraction behavior, resistance-in-series (RIS) model was developed to predict the re-extraction efficiency at steady-state conditions. First of all, a three- parameter correlation was defined for quantitative description of droplet size. The main factors affecting the re-extraction efficiency of PEN G were superficial Reynolds number and phase ratio. The re-extraction efficiency of PEN G reached 99% or above at Re h > 934 and R > 0.08. Meanwhile, the degradation rate of PEN G (D) decreased to 0.5% when Re h was 934. Compared with the re-extraction performance of the batch extractor, less residence time was needed and the degradation rate decreased 50%. The theoretical re-extraction efficiency (RE T ) was in good agreement with the experimental data. © 2009 Elsevier B.V. All rights reserved. 1. Introduction Penicillin G (PEN G), belongs to the -lactam class of antibiotics, is the first antibiotic for curing human bacterial disease, which can inhibit bacterial cell wall synthesis [1–2]. It is widely applied in clin- ical treatment because of its high anti-bactericidal activity, broad spectrum, low toxicity, and excellent distribution. In addition, PEN G is the raw material of the semi-synthetic penicillins [3]. There- fore, the commercial demand of PEN G increased drastically in the past two decades. Conventional process of PEN G usually involves five distinct steps: filtration, solvent extraction, re-extraction, crystallization, and drying. The re-extraction process is one of the most important steps. The process is that undissociated PEN G, which is extracted from the fermentation broth by physical extraction with n-butyl acetate, return aqueous phase to react with carbonate anions. Due to the weakness of -lactam ring, PEN G is unstable, and decomposes irreversibly at alkaline conditions [4], and the main degradation product of PEN G was penicilloic acid [2,5]. In addition, it is reported that these degradation products are related to 3–5% ∗ Corresponding author. Tel.: +86 10 6255 4264; fax: +86 10 6255 4264. E-mail address: hzliu@home.ipe.ac.cn (H. Liu). of patients of penicillin allergic reactions [5,6]. Some processes are developed to increase mass-transfer rate and reduce side products. First of all, reactive extraction of PEN G was applied at pH 5.0, but the solubility of the extractant is too high to be utilized in industry [6–8]. For this reason, emulsion liquid membrane (ELM) is adopted and provided large interfacial area. Meanwhile, one step recovery of PEN G is carried out efficiently by eliminating equilibrium lim- itation, whereas de-emulsification step of re-extraction is difficult to be operated [9–10]. In addition, some extractors are used for the process such as centrifugal extractors [11] and Karr column [12–14]. Nevertheless, centrifugal extractor and Karr column are expensive and difficult to maintain. Although hollow fiber mem- brane contactor has many advantages such as continuous operation free dispersion, small equipment volume, which is used for the extraction and re-extraction of PEN G, the resistance of membrane film results in a slower mass-transfer rate in the free dispersion pro- cess, and membrane materials are easy to be corroded by organic solvent in comparison with other processes [15–16]. As a result, up to now, large stirred tank extractor has been used in the phar- maceutical industry, and the part of PEN G is decomposed in the re-extraction process. Based on the above analysis, a fundamental factor of PEN G re-extraction is mass-transfer rate. Micro-dispersion droplets have many advantages, such as larger specific interfacial area, 0376-7388/$ – see front matter © 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.memsci.2009.10.001