Application of solvent extraction technology in penicillin extraction

Mar 13, 2024

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Penicillin is also known as penicillin G, penicillin, penicillin, etc. Its main source is Penicillium culture fluid. The ampicillin contains an appropriate amount of penicillin, which can play a certain bactericidal effect during the cell growth process. Due to its strong bactericidal properties and low toxicity, penicillin has been a long-lasting presence in the antibiotic market and has become a first-line antibacterial drug widely used around the world.

 

Penicillin G is currently one of the most widely used and produced antibiotics, and is also an important raw material for the production of other semi-synthetic antibiotics. At present, microbial fermentation is mostly used in the industrial production of penicillin G, and solvent extraction is the traditional extraction process.

 

Solvent extraction is an important unit operation that has been widely used in the pharmaceutical industry. From the production of the first clinically used antibiotic, penicillin, to the present, solvent extraction has been used in antibiotic extraction for more than 50 years. In addition to penicillin, there are dozens of other antibiotics including erythromycin, medinomycin, and lincomycin. All antibiotics are extracted using solvent extraction. With the development of the antibiotic industry, the research and application of solvent extraction technology have developed rapidly.

 

Penicillin free acid is easily soluble in organic solvents, while penicillin salts are easily soluble in water. Utilizing this property, penicillin is transferred into an organic solvent under acidic conditions, the pH is adjusted, and then transferred into a neutral aqueous phase, and the extraction is repeated several times to purify and concentrate. Choose an organic solvent with a high partition coefficient for penicillin. Butyl acetate and amyl acetate are commonly used in industry. Extract 2-3 times. When extracting butyl acetate from fermentation broth, select pH 1.8-2.0. When back-extracting butyl acetate into aqueous phase, select pH 6.8-7.4. The volume ratio of fermentation filtrate to butyl acetate is 1.5-2.1, that is, the one-time concentration multiple is 1.5-2.1. In order to avoid pH fluctuations, sulfate and carbonate buffers were used for stripping. The ratio of fermentation broth to solvent is 3-4. After several extractions, it was concentrated 10 times, and the concentration almost reached the crystallization requirements. The total extraction yield is about 85%. The obtained filtrate is usually extracted twice, using 10% sulfuric acid to adjust the pH to 2.0~3.0, and adding butyl acetate in a dosage of one third of the filtrate volume. During back extraction, sodium bicarbonate solution is used to adjust the pH to 7.0~8.0. . During primary butyl ester extraction, since the filtrate contains a large amount of protein, a demulsifier is usually added to prevent emulsification. For the first extraction, if there is protein, add 0.05-0.1% emulsifier PPB.