Dynamic Modelling and Optimisation of the Batch Enzymatic Synthesis of Amoxicillin

Abstract

Amoxicillin belongs to the β-lactam family of antibiotics, a class of highly consumed pharmaceutical products used for the treatment of respiratory and urinary tract infections, and is listed as a World Health Organisation (WHO) “Essential Medicine”. The demonstrated batch enzymatic synthesis of amoxicillin is composed of a desired synthesis and two undesired hydrolysis reactions of the main substrate (6-aminopenicillanic acid (6-APA)) and amoxicillin. Dynamic simulation and optimisation can be used to establish optimal control policies to attain target product specification objectives for bioprocesses. This work performed dynamic modelling, simulation and optimisation of the batch enzymatic synthesis of amoxicillin. First, kinetic parameter regression at different operating temperatures was performed, followed by Arrhenius parameter estimation to allow for non-isothermal modelling of the reaction network. Dynamic simulations were implemented to understand the behaviour of the design space, followed by the formulation and solution of a dynamic non-isothermal optimisation problem subject to various product specification constraints. Optimal reactor temperature (control) and species concentration (state) trajectories are presented for batch enzymatic amoxicillin synthesis.