Crystal shape modification via cycles of growth and dissolution in a tubular crystallizer

Peter Neugebauer, Javier Cardona, Maximilian O. Besenhard, Anna Peter, Heidrun Gruber-Woelfler, Christos Tachtatzis, Alison Cleary, Ivan Andonovic, Jan Sefcik, Johannes G. Khinast

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Besides size and polymorphic form, crystal shape takes a central role in engineering advanced solid materials for pharmaceutical and chemical industry. This work demonstrates how multiple cycles of growth and dissolution can manipulate the habit of an acetylsalicylic acid crystal population. Considerable changes of the crystal habit could be achieved within minutes due to rapid cycling, i.e., up to 25 cycles within <10 min. The required fast heating and cooling rates were facilitated using a tubular reactor design allowing for superior temperature control. The face specific interactions between solvent and the crystals’ surface result in face specific growth and dissolution rates and hence alterations of the final shape of the crystals in solution. Accurate quantification of the crystal shapes was essential for this work, but is everything but easy. A commercial size and shape analyser had to be adapted to achieve required accuracy. Online size, and most important shape, analysis was achieved using an automated microscope equipped with a flow-through cell, in combination with a dedicated image analysis routine for particle tracking and shape analysis. Due to the implementation of this analyser, capable of obtaining statistics on the crystals’ shape while still in solution (no sampling and manipulation required), the dynamic behaviour of the size shape distribution could be studied. This enabled a detailed analysis of the solvent’s effect on the change in crystal habit.
LanguageEnglish
Pages4403–4415
Number of pages13
JournalCrystal Growth and Design
Volume18
Issue number8
DOIs
Publication statusPublished - 15 Jun 2018

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Crystallizers
dissolving
Dissolution
Crystals
cycles
crystals
habits
acetylsalicylic acid
reactor design
temperature control
Chemical industry
image analysis
crystal surfaces
Temperature control
Drug products
Image analysis
Aspirin
manipulators
Microscopes
industries

Keywords

  • crystal engineering
  • shape control
  • temperature cycling
  • particle tracking
  • online shape analysis
  • choice of solvent

Cite this

Neugebauer, Peter ; Cardona, Javier ; Besenhard, Maximilian O. ; Peter, Anna ; Gruber-Woelfler, Heidrun ; Tachtatzis, Christos ; Cleary, Alison ; Andonovic, Ivan ; Sefcik, Jan ; Khinast, Johannes G. / Crystal shape modification via cycles of growth and dissolution in a tubular crystallizer. In: Crystal Growth and Design. 2018 ; Vol. 18, No. 8. pp. 4403–4415.
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Crystal shape modification via cycles of growth and dissolution in a tubular crystallizer. / Neugebauer, Peter; Cardona, Javier; Besenhard, Maximilian O.; Peter, Anna; Gruber-Woelfler, Heidrun; Tachtatzis, Christos; Cleary, Alison; Andonovic, Ivan; Sefcik, Jan; Khinast, Johannes G.

In: Crystal Growth and Design, Vol. 18, No. 8, 15.06.2018, p. 4403–4415.

Research output: Contribution to journalArticle

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T1 - Crystal shape modification via cycles of growth and dissolution in a tubular crystallizer

AU - Neugebauer, Peter

AU - Cardona, Javier

AU - Besenhard, Maximilian O.

AU - Peter, Anna

AU - Gruber-Woelfler, Heidrun

AU - Tachtatzis, Christos

AU - Cleary, Alison

AU - Andonovic, Ivan

AU - Sefcik, Jan

AU - Khinast, Johannes G.

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