PENICILLIN STABILITY IN DIFFERENT BUFFER SOLUTIONS

Effects of structure on penicillin stability in different buffer solutions



Effects of structure on penicillin stability in different buffer solutions

Introduction

The isolation of penicillin from the culture broth is carried out by extraction of filtered broth with organic solvents such as n-butyl acetate, n-amyl acetate, isobutyl methyl ketone and butanol at low pH values. Strict care must be taken that aqueous penicillin solutions are kept at pH 1.8-2.5 for only seconds. Centrifugal extractors are used to keep the contact time as short as possible. After the extraction, the penicillin is returned to the buffer and acidified. It is re-extracted with a smaller volume at pH 6.8-8.0 in a carbonate or phosphate buffer.

The concentrated penicillin is brought into aqueous solution, again. Penicillin is crystallized from this solution. Penicillin is highly sensitive to heat, acids and penicillinases. It is a weak acid (pKa=2.75) and widely used as the raw material for the production of semisynthetic penicillins . It is necessary to work rapidly at the lowest possible temperatures and avoid the infection of penicillin during isolation process(Kheirolomoom, 2008, pp. 81).

The decomposition of penicillin in an aqueous solution is mainly dependent on temperature and pH. The extraction was carried out using centrifugal extractors and to avoid losses, reactive extraction by secondary amines was employed. It was possible to carry out the extraction of penicillin at pH 5 and the re-extraction at pH 7.5 when such amines were used. However, the conventional extraction process is carried out at pH 1.8-2.5 . The cell-free medium temperature is set at 0-5°C, due to the instability of penicillin at higher temperatures. The degradation of penicillin in an aqueous solution is mainly due to the dissociation of carboxyl group which transforms the active penicillin to inactive products such as penillic acid which is an inactivated product with an open ß-lactam ring . During the isolation of penicillin , 10-15% of the product is lost. The decomposition of penicillin is a key factor in penicillin losses. The stability of penicillin is necessary for reduction of such losses(Cornish-Bowden 2007 pp. 21).

The stability of penicillin in aqueous solutions was discussed by different investigators. The effect of buffers and surfactants on degradation of penicillins were previously described ,. The recent reviews include the stability of penicillin in the presence of carriers in reactive extraction and the effect of neutral phosphorous esters in physical extraction as well as the effect of pH and mechanical stress in reactive extraction of penicillin regarding its decomposition reaction. In the present article, using the experimental results a second-order model was proposed to predict the combined effects of pH and temperature on penicillin decomposition. The model is more precise in comparison with the reported linear models can be applied for a broader range of pH and temperature values( Kazan 2006 pp. 691).

Materials and methods

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