Model development for enzymatic reactive crystallization of β-lactam antibiotics: a reaction–diffusion-crystallization approach

Abstract

A mathematical model for production of β-lactam antibiotics via enzymatic reactive crystallization is developed, and its application for catalyst and process design is discussed.

Magnetic separation of immobilized biocatalyst enables continuous manufacturing with a solids-forming reaction

“…High PGA loading per unit of immobilized particle has been shown to have an adverse effect on β-lactam synthesis kinetics and selectivity. 36 However, for magnetic separation, increased magnetic bead concentration increases risk of clogging. Thus, catalytic and separation efficiency must be balanced.…”

“…34 For catalytic particles, increased size typically results in reduced performance and mass-transfer limitations. 35,36 To avoid these issues, the addition of bead magnetic properties provides an additional variable to manipulate the separation design. Magnetic separation has been implemented in cell separation, [37][38][39] DNA isolation, 40 and iron ore isolation; 41 however, examples of continuous magnetic separation or magnetic separation of typical immobilized catalyst and crystal sizes (10-1000 μm) are rare.…”

Reactor Design and Optimization of α-Amino Ester Hydrolase- Catalyzed Synthesis of Cephalexin

“…Specifically, consumption of cephalosporins grew 94% between 2000 and 2010 and global production of cephalexin currently exceeds approximately 4,000 tons each year ( Laxminarayan 2014 ; Van Boeckel et al, 2014 ). Recent studies have focused specifically on developing a continuous operation in simulations of continuous reactor designs using both enzymatic reaction and crystallization kinetics ( Valencia et al, 2012 ; Encarnación-Gómez et al, 2016 ; McDonald et al, 2017 ; McDonald et al, 2019a ; McDonald et al, 2019b ; McDonald et al, 2019c ; Cuthbertson et al, 2019 ; Salami et al, 2020 ).…”

“…Accurate models for downstream processing of active pharmaceutical ingredients (APIs) rely on proper modelling of all upstream units, including reactors. Several studies have discussed complex reaction-isolation systems ( Salami et al, 2020 ; Ma et al, 2021 ) as well as upstream process modelling for generation of reaction substrates ( Caşcaval et al, 2012 ) and downstream process modelling from fermentation broths ( Likozar et al, 2012 ; Likozar et al, 2013 ), which could all be coupled with reactor modelling for whole process models of API production and isolation.…”