Prevention of Penicillin Polymerization

Because of the immunologic effects of penicillin polymers which are strongly supposed to be of clinical importance, their presence in clinically used penicillin preparations should be controlled and kept at the lowest possible level. 

For penicillins without an amino group in the side chain, the polymerization is thought to depend strongly on the presence of the reactive penicillenic acid. Thus attempts to depress the polymerization of these penicillins should primarily be concerned with preventation of formation of penicillenic acid. Since the compound is formed by an acid-catalyzed isomerization, its formation can be depressed by keeping the pH of penicillin solutions to at least pH 6, e.g., by using a citrate buffer. 

Since the introduction of ampicillin in 1961, a great number of broad-spectrum aminopenicillins have been developed and certainly will continue to be developed. 

It seems relevant to stress that when assessing the clinical usefulness of such antibiotics, account should be taken of the polymerizing propensity of the penicillins in addition to other factors normally considered. 

For cephalosporins containing an amino group in the C7 side chain such as cephalexin, cephaloglycin, and cephradine, a polymerization can be imagined to occur by intermolecular aminolysis in the same way as the polymerization of am-picillin and other aminopenicillins. Such as reaction can, however, be expected to be much less effective for the cephalosporins since an autocatalyzed intramolecular aminolysis with the formation of piperazine-2,5-dione derivatives may occur to a much larger extent than an intermolecular aminolysis (Bundgaard 1976 c, d). 

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