Precipitation of clavulanic acid from fermentation broth with potassium 2-ethyl hexanoate salt

• Published in: Separation and purification technology Vol. 66; no. 3; pp. 598 - 605
• Main Authors: Hirata, D.B., Oliveira, J.H.H.L., Leão, K.V., Rodrigues, M.I., Ferreira, A.G., Giulietti, M., Barboza, M., Hokka, C.O.
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier B.V 07.05.2009; Elsevier
• Subjects: Applied sciences; Biological and medical sciences; Biotechnology; Chemical engineering; Clavulanic acid; Exact sciences and technology; Fundamental and applied biological sciences. Psychology; Methods. Procedures. Technologies; Others; Potassium 2-ethyl hexanoate; Potassium clavulanate; Precipitation; Purification; Various methods and equipments; Potassium clavulanate; Precipitation; Purification; Potassium 2-ethyl hexanoate; Clavulanic acid; Organic solvent; Antibiotic; Extract; Fermentation; Pharmaceutical industry; Drying
• ISSN: 1383-5866; 1873-3794
• DOI: 10.1016/j.seppur.2009.01.010

This paper describes a direct precipitation reaction of clavulanic acid (CA) using potassium 2-ethyl hexanoate salt. Clavulanic acid is an important molecule produced by the pharmaceutical industry to overcome problems relating to bacterial resistance to antibiotics. However, precipitation of this organic compound has been little studied and, unlike inorganic compounds, its isolation and precipitation usually involve a complex and meticulous process. The purpose of this work was to improve the purification process and increase the yield of CA from fermented broth by examining the influence of the combined concentrations of clavulanic acid (in organic solvent) and potassium 2-ethyl hexanoate on the potassium clavulanate precipitation reaction. Clavulanic acid was extracted at temperatures below 20 °C and preferably close to 15 °C in the water-immiscible organic solvent ethyl acetate. The drying step was performed with a suitable desiccant to produce an insoluble salt of potassium clavulanate. The resulting precipitate was crystalline and stable, a finding that was confirmed by an NMR 1H analysis.