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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.
Original language | English |
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Pages (from-to) | 4403–4415 |
Number of pages | 13 |
Journal | Crystal Growth and Design |
Volume | 18 |
Issue number | 8 |
DOIs | |
Publication status | Published - 15 Jun 2018 |
Keywords
- crystal engineering
- shape control
- temperature cycling
- particle tracking
- online shape analysis
- choice of solvent
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Projects
- 1 Finished
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Intelligent Decision Support Technologies for Continuous Manufacture
Andonovic, I., Bititci, U., Florence, A., Gachagan, A., Johnston, B., Marshall, S., Michie, C., Mulholland, A., Nordon, A., Sefcik, J. & Vasile, M.
Bayer Healthcare AG, Novartis Pharma AG, AstraZeneca UK Limited, Glaxo Smithkline (UK), EPSRC (Engineering and Physical Sciences Research Council)
1/02/13 → 31/07/18
Project: Research