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Related Experiment Video

Updated: Aug 23, 2025

Crystallization of Membrane Proteins in Lipidic Mesophases
11:53

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Published on: March 28, 2011

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Strategy for Fast Decision on Material System Suitability for Continuous Crystallization Inside a Slug Flow

Anne Cathrine Kufner1, Adrian Krummnow2,3, Andreas Danzer2

  • 1Department of Biochemical and Chemical Engineering, Laboratory of Plant and Process Design, TU Dortmund University, D-44227 Dortmund, Germany.

Micromachines
|October 27, 2022
PubMed
Summary

This study presents a rapid strategy for continuous crystallization using slug flow crystallizers (SFCs). It enables efficient production of high-quality active pharmaceutical ingredients (APIs) with minimal experimental effort.

Keywords:
contact anglecontinuous crystallizationmicrofluidicsslug flowsolid–liquid interactionsolubility modeling

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Area of Science:

  • Chemical Engineering
  • Materials Science
  • Process Chemistry

Background:

  • Two-phase flow in micro/mini-structured devices is crucial for manufacturing and instrumentation.
  • Slug flow offers advantages like narrow residence time distribution, enhanced mixing, and particle suspension for high-quality crystallization.
  • Slug flow crystallizers (SFCs) are promising for small-scale continuous crystallization of active pharmaceutical ingredients (APIs).

Purpose of the Study:

  • To develop a time-efficient strategy for rapid crystallization in SFCs.
  • To minimize experimental effort in achieving desired solid products via slug flow crystallization.
  • To establish a generalizable approach for various material systems in SFCs.

Main Methods:

  • Heuristic pre-selection of solvents and solvent mixtures.
  • Verification of slug flow stability using static contact angle and dynamic flow behavior.
  • Modeling temperature-dependent solubility with perturbed-chain statistical associating fluid theory (PC-SAFT).

Main Results:

  • Successfully demonstrated the strategy for amino acids (l-alanine, l-arginine) and paracetamol.
  • Validated the approach for both binary and ternary solvent systems.
  • Confirmed the general applicability of the strategy across different material systems.

Conclusions:

  • The presented strategy enables rapid and efficient crystallization in SFCs.
  • This approach reduces experimental workload for process development.
  • The method is adaptable for diverse materials, facilitating broader SFC application.