Solution crystallization kinetics of 6-aminopenicillanic acid

Semisynthetic penicillins, derived from 6-aminopenicillanic acid (APA), constitute an important group of antibiotics. APA is produced by enzymatic hydrolysis of penicillin G (PenG). This study concerns the determination of the crystallization kinetics of APA in the presence of other components that may be present after the PenG hydrolysis, i.e., remaining PenG and the byproduct phenylacetic acid. This evaluation is based on the analyses of growth rate and crystal size distribution, at pH 4 and 5. The results show that the impurities have no significant influence on the APA crystallization, within the range of pH and impurity concentrations evaluated. A mathematical model, based on the population balance, gives a good prediction of the crystallization rate and crystal size distribution with a single set of parameters.