Development, optimization and scale-up of stereo-selective enzymatic Baeyer–Villiger oxidation of pyrmetazole to esomeprazole active ingredient in an industrial-scale slurry reactor

[Display omitted] An industrial-scale stereo-selective enzymatic oxidation process for the conversion of pyrmetazole to esomeprazole was developed and optimized. Slurry-to-slurry stages are highly demanding synthetic operations due to several deteriorating factors: competing equilibria, mass transfe...

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Bibliographic Details
Published in:Journal of industrial and engineering chemistry (Seoul, Korea) 2019, 72(0), , pp.214-221
Main Authors: Herga, Marko, Gasparič, Aleš, Bitenc, Marko, Pohar, Andrej, Likozar, Blaž
Format: Article
Language:English
Subjects:
Computational fluid dynamics
Crystallization downstream process
Enzymatic oxidation reaction
Esomeprazole active ingredient
Industrial slurry reactor
Pyrmetazole substrate molecule
화학공학
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Summary:[Display omitted] An industrial-scale stereo-selective enzymatic oxidation process for the conversion of pyrmetazole to esomeprazole was developed and optimized. Slurry-to-slurry stages are highly demanding synthetic operations due to several deteriorating factors: competing equilibria, mass transfer limitations and long-term bio-catalytic activity. Challenging characteristics of this bio-oxidation included foaming, thickening, continuous dynamic changes in viscosity, mass transport, and bio-catalyst inactivation. By screening pH, optimization of reactant loading ratios, and modification of control, crucial production attributes of materials, such as substrate particle size, were controlled and better batch-to-batch stability and scale-up was achieved.
ISSN:1226-086X
1876-794X
DOI:10.1016/j.jiec.2018.12.020