Mathematical modeling of batch and semibatch reactors for the enzymic synthesis of amoxicillin

Abstract

The performance of batch and semibatch reactors, under optimal operational conditions of amoxicillin (AN) enzymic synthesis at 25 °C and pH 6.5, were compared. Simulations for a batch reactor indicate that there are two sets of optimal operational conditions, if we consider productivity and global yield ( Y AN, AB) with respect to the ester substrate: (i) low initial concentration of ester and high initial concentration of 6-aminopenicillanic acid (6-APA); (ii) high initial concentration of ester and high initial concentration of 6-APA. Simulations for a semibatch reactor, using the hybrid-neural network model, indicated a consumption of the formed antibiotic. Such pattern was not observed experimentally and was caused by the lack of information during neural network training procedure. This problem was overcome by including new sets of experimental data in the learning phase, performed in a batch reactor in the presence of different initial concentrations of substrates and products. Results for the semibatch reactor indicated there are different sets of optimal operational conditions, if we consider local selectivity, performance index ( I NH), and global yield. Unfortunately, the point of highest local selectivity and performance index is not the one of highest global yield. Therefore, the choice of initial operational conditions for the batch or semibatch production of amoxicillin is connected to an economical evaluation. The semi-continuous operation of the integrated reactor (reaction+crystallization) provided better results than the batch mode.