Phase diagram determination and process development for continuous antisolvent crystallizations

Corin Mack, Johannes Hoffmann, Jan Sefcik, Joop H. ter Horst

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)
31 Downloads (Pure)

Abstract

The development of an antisolvent crystallization process requires the construction of an accurate phase diagram for this ternary system of compound, solvent and antisolvent, preferably as a function of temperature. This study gives an efficient methodology to systematically determine such antisolvent phase diagrams, exemplified with four model compounds: Sodium bromate, DL-Asparagine Monohydrate, Mefenamic acid and Lovastatin. Using clear point temperature measurements, single solvent and mixed solvent-antisolvent solubilities are obtained, showing strongly non-linear solubility dependencies as well as more complex solubility behaviour as a function of antisolvent fraction. A semi-empirical model equation is used to describe the phase diagram of the antisolvent crystallization system as a function of both temperature and antisolvent fraction. The phase diagram model then allows for the identification of condition ranges for optimal productivity, yield, and suspension density in continuous antisolvent crystallization processes.
Original languageEnglish
Article number1102
Number of pages15
JournalCrystals
Volume12
Issue number8
Early online date6 Aug 2022
DOIs
Publication statusPublished - 6 Aug 2022

Keywords

  • solubility in mixed solvents
  • antisolvent crystallization
  • continuous crystallization
  • crystallization process development

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