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Comparative Study of Different Crystallization Methods in the Case of Cilostazol Crystal Habit Optimization

Institute of Pharmaceutical Technology and Regulatory Affairs, Faculty of Pharmacy, University of Szeged, Eötvös Str. 6, H-6720 Szeged, Hungary
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Crystals 2019, 9(6), 295; https://doi.org/10.3390/cryst9060295
Received: 10 May 2019 / Revised: 3 June 2019 / Accepted: 4 June 2019 / Published: 5 June 2019
(This article belongs to the Special Issue Anti-Solvent Crystallization)
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Abstract

The therapeutic usage of cilostazol is limited owing to its poor aqueous solubility and oral bioavailability. Our aim was to produce cilostazol crystals with small average particle size; besides suitable roundness, narrow particle size distribution and stable polymorphic form to increase its dissolution rate and improve processability. Different conventional crystallization methods with or without sonication were compared with impinging jet crystallization combined with cooling, and the optimization of the various parameters was also implemented. The effects of post-mixing time and temperature difference were studied by means of a full factorial design. The physical properties of powder particles were characterized by, i.a., XRPD, DSC and SEM. The dissolution rate and the contact angle of solid surfaces were also determined to elucidate the relationship between wettability and dissolution. It was observed that impinging jet crystallization combined with cooling is a very effective and reproducible method for reducing the particle size of cilostazol. This method resulted in significantly smaller particle size (d(0.5) = 3–5 μm) and more uniform crystals compared to the original ground material (d(0.5) = 24 μm) or the conventional methods (d(0.5) = 8–14 μm), and it also resulted in a stable polymorphic form and enhanced the dissolution rate. View Full-Text
Keywords: crystal habit; particle size reduction; cilostazol; impinging jet crystallization; dissolution rate; polymorphism crystal habit; particle size reduction; cilostazol; impinging jet crystallization; dissolution rate; polymorphism
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Tari, T.; Szabó-Révész, P.; Aigner, Z. Comparative Study of Different Crystallization Methods in the Case of Cilostazol Crystal Habit Optimization. Crystals 2019, 9, 295.

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