UNIFAC Model for Liquid-Liquid Phase Equilibrium of Penicillin G and 6-APA System

Lienda Aliwarga, Herri Susanto, Reynard Reynard, Agnes Veronica Victoria


This study investigated the effect of pH and type of solvent on liquid-liquid phase equilibrium in the system of pure penicillin G and mixed penicillin G with 6-APA. Penicillin G extraction was carried out in a pH range of 2.0–5.0 at 4 oC using several types of solvents. The liquid-liquid phase equilibrium mathematical model is prepared assuming that a single stage of thermodynamic equilibrium occurs in a batch process of liquid-liquid extraction. The coefficient of activity was calculated by the UNIFAC method. From the experiment, it was found that the extraction process of penicillin G was strongly influenced by pH of the solution. The highest yield of extraction was achieved with different solvents in the two types of solution. For pure penicillin G system, the highest yields was obtained in n-butyl acetate solvent (95.51%) while for penicillin G mixture with 6-APA, it was obtained in methyl iso-butyl ketone solvent (92.6%). The UNIFAC model have been tested against five three-component liquid-liquid phase equilibrium systems at pH 2.0 and 2.5. It was able to estimate the concentration of penicillin G in the organic phase with a relatively average error between experiment and calculation of 8.32%


Extraction; penicillin G; 6-APA; UNIFAC


Carleysmith SW, Lilly MD. 2018. Deacylation of benzylpenicillin by immobilized penicillin acylase in a continuous four-stage stirred-tank reactor. Biotechnology and Bioengineering. 21(6): 1057–1073. https://doi.org/10.1002/bit.260210610.

Daubert TE, Danner RP. 1985. Data Compilation Tables of Properties of Pure Compounds. New York.

Deo YM, Gaucher GM. 2018. Semicontinuous and continuous production of penicillin-G by Penicillium chrysogenum cells immobilized in κ-carrageenan beads. Biotechnology and Bioengineering. 26(3): 285–295. https://doi.org/10.1002/bit.260260314.

Dhal PK, Babu GN, Sudhakaran S, Borkar PS. 2018. Immobilization of penicillin acylase by covalent linkage on vinyl copolymers containing epoxy groups. Die Makromolekulare Chemie, Rapid Communications. 6(2): 91–95. https://doi.org/10.1002/marc.1985.030060208.

Haagensen P, Karlsen LG, Petersen J, Villadsen J. 2018. The kinetics of penicillin-V deacylation on an immobilized enzyme. Biotechnology and Bioengineering. 25(7): 1873–1895. https://doi.org/10.1002/bit.260250715.

Harvey W, Blanch SD, Daniel I, CW. 2018. Book Review: Comprehensive Biotechnology. The Principles, Applications and Regulations of Biotechnology in Industry, Agriculture and Medicine. Editor-in-chief: M. Moo-Young. Angewandte Chemie International Edition in English. 26(6): 588. https://doi.org/10.1002/anie.198705881.

Jing D, Wang J, Wang Y. 2010. Solubility of penicillin sulfoxide in different solvents. Journal of Chemical and Engineering Data. 55(1): 508–509. https://doi.org/10.1021/je900326e.

Karlsen LG, Villadsen J. 2018. Optimization of a reactor assembly for the production of 6-APA from penicillin-V. Biotechnology and Bioengineering. 26(12): 1485–1491. https://doi.org/10.1002/bit.260261213.

Park JM, Choi CY, Seong BL, Han MH. 2018. The production of 6-aminopenicillanic acid by a multistage tubular reactor packed with immobilized penicillin amidase. Biotechnology and Bioengineering. 24(7): 1623–1637. https://doi.org/10.1002/bit.260240714.

Reschke M, Schügerl K. 1984a. Reactive extraction of penicillin I: Stability of penicillin G in the presence of carriers and relationships for distribution coefficients and degrees. The Chemical Engineering Journal. 28(1): B1–B9. https://doi.org/https://doi.org/10.1016/0300-9467(84)85015-7.

Reschke M, Schügerl K. 1984b. Reactive extraction of penicillin II: Distribution coefficients and degrees of extraction. The Chemical Engineering Journal. 28(1): B11–B20. https://doi.org/https://doi.org/10.1016/0300-9467(84)85016-9.

Sheldon RA, Van Pelt S. 2013. Enzyme immobilisation in biocatalysis: why, what and how. Chem. Soc. Rev. 42: 6223–6235.

Singh V, Goyal SG. 2014. Penicillin G Acylase, a biocatalyst and its potential application. International Journal of Scientific & Engineering Research. 5(5): 153–158.

Sørensen JM, Magnussen T, Rasmussen P, Fredenslund A. 1979. Liquid-liquid equilibrium data: Their retrieval, correlation and prediction Part I: Retrieval. Fluid Phase Equilibria. 2(4): 297–309. https://doi.org/https://doi.org/10.1016/0378-3812(79)80015-1.

Su M, Sun H, Zhao Y, Lu A, Cao X, Wang J. 2016. Degradation Kinetics and Mechanism of a β-Lactam Antibiotic Intermediate, 6-Aminopenicillanic Acid, in a New Integrated Production Process. Journal of Pharmaceutical Sciences. 105(1): 139–146. https://doi.org/10.1016/j.xphs.2015.11.026

Szewczuk A, Ziomek E, Mordarski M, Siewiński M, Wieczorek J. 2018. Properties of penicillin amidase immobilized by copolymerization with acrylamide. Biotechnology and Bioengineering. 21(9): 1543–1552. https://doi.org/10.1002/bit.260210904.

Warburton D, Dunnill P, Lilly MD. 2018. Conversion of benzylpenicillin to 6-aminopenicillanic acid in a batch reactor and continuous feed stirred tank reactor using immobilized penicillin amidase. Biotechnology and Bioengineering. 15(1): 13–25. https://doi.org/10.1002/bit.260150103.

Wei T, Wang C, Du S, Wu S, Li J, Gong J. 2015. Measurement and correlation of the solubility of penicillin V potassium in ethanol + water and 1-butyl alcohol + water systems. Journal of Chemical and Engineering Data. 60(1): 112–117. https://doi.org/10.1021/je5008422.

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DOI: 10.15408/jkv.v5i2.9869


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