Comparative study of different crystallization methods in the case of cilostazol crystal habit optimization

Research output: Article

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.

Original languageEnglish
Article number295
JournalCrystals
Volume9
Issue number6
DOIs
Publication statusPublished - jún. 1 2019

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habits
Crystallization
dissolving
Dissolution
crystallization
Crystals
optimization
Particle size
crystals
Cooling
factorial design
cooling
bioavailability
Sonication
wettability
particle size distribution
solid surfaces
Particle size analysis
Powders
Contact angle

ASJC Scopus subject areas

  • Chemical Engineering(all)
  • Materials Science(all)
  • Condensed Matter Physics
  • Inorganic Chemistry

Cite this

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title = "Comparative study of different crystallization methods in the case of cilostazol crystal habit optimization",
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.",
keywords = "Cilostazol, Crystal habit, Dissolution rate, Impinging jet crystallization, Particle size reduction, Polymorphism",
author = "T{\'i}mea Tari and P. Szab{\'o}-R{\'e}v{\'e}sz and Z. Aigner",
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AB - 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.

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