Effect of particle size reduction on dissolution and oral absorption of a poorly water-soluble drug, cilostazol, in beagle dogs

Jun Ichi Jinno, Naoki Kamada, Masateru Miyake, Keigo Yamada, Tadashi Mukai, Masaaki Odomi, Hajime Toguchi, Gary G. Liversidge, Kazutaka Higaki, Toshikiro Kimura

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348 Citations (Scopus)

Abstract

The purpose of the present study was to investigate the effects of particle size on the dissolution and oral absorption of cilostazol. Three types of suspensions having different particle size distributions were prepared of the hammer-milled, the jet-milled cilostazol crystals and the NanoCrystal® spray-dried powder of cilostazol. In vitro dissolution rate of cilostazol was significantly increased by reducing the particle size. The dissolution curves of the cilostazol suspensions were in good agreement with the simulation based on the Noyes-Whitney equation. The bioavailability of cilostazol after oral administration to dogs was increased with reducing the particle size. While positive food effect on the absorption was observed for the suspensions made of the hammer-milled and the jet-milled crystals, no significant food effect was found for the suspension made of the NanoCrystal® cilostazol spray-dried powder. These results could be qualitatively predicted from the in vitro dissolution data using the bio-relevant media, FaSSIF and FeSSIF. In conclusion, the NanoCrystal® technology is found to be efficient to improve the oral bioavailability of cilostazol and to avoid the food effect on the absorption.

Original languageEnglish
Pages (from-to)56-64
Number of pages9
JournalJournal of Controlled Release
Volume111
Issue number1-2
DOIs
Publication statusPublished - Mar 10 2006

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Keywords

  • Bioavailability
  • Cilostazol
  • Dissolution
  • Food effect
  • NanoCrystal
  • Particle size reduction

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Jinno, J. I., Kamada, N., Miyake, M., Yamada, K., Mukai, T., Odomi, M., Toguchi, H., Liversidge, G. G., Higaki, K., & Kimura, T. (2006). Effect of particle size reduction on dissolution and oral absorption of a poorly water-soluble drug, cilostazol, in beagle dogs. Journal of Controlled Release, 111(1-2), 56-64. https://doi.org/10.1016/j.jconrel.2005.11.013