Technoeconomic MINLP Optimisation of Liquid-Liquid Extraction (LLE) Cascades for Continuous Pharmaceutical Manufacturing (CPM) of Atropine

S. Diab, Nikolaos Mytis, Andreas G. Boudouvis, Dimitrios I. Gerogiorgis

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Continuous pharmaceutical manufacturing (CPM) has the potential to revolutionise the production of active pharmaceutical ingredients (APIs), offering operational and economic benefits over the currently dominant batch methods implemented by industry. Atropine is a nerve agent API, whose demonstrated continuous flow synthesis facilitates process modelling and optimisation. This work implements MINLP optimisation for total cost minimisation of the upstream CPM of atropine for rapid process synthesis. The process model considers reactor design from regressed reaction kinetic parameters, solute partitioning between LLE phases for different solvent systems, UNIFAC-modelled ternary liquid-liquid equilibria and mass transfer correlations for continuous LLE design. Optimisation results indicate toluene as the best (cost optimal) LLE solvent choice. This work demonstrates the utility of the described methodology for rapid process synthesis and comparative technoeconomic evaluation in early CPM process development stages.

Original languageEnglish
Title of host publication29th European Symposium on Computer Aided Process Engineering
EditorsAnton A. Kiss, Edwin Zondervan, Richard Lakerveld, Leyla Özkan
PublisherElsevier B.V.
Pages211-216
Number of pages6
Volume46
ISBN (Electronic)978-0-12-819939-8
DOIs
Publication statusE-pub ahead of print - 25 Jul 2019

Publication series

NameComputer Aided Chemical Engineering
Volume46
ISSN (Print)1570-7946

Keywords

  • Atropine
  • Continuous pharmaceutical manufacturing (CPM)
  • Economic analysis
  • MINLP
  • Superstructure

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