In vitro-in vivo correlation for wet-milled tablet of poorly water-soluble cilostazol

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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69 Citations (Scopus)


The purpose of the present study was to investigate oral bioavailability of an immediate release tablet containing wet-milled crystals of a poorly water-soluble drug, cilostazol, and to establish in vitro-in vivo correlation. Sub-micron sized cilostazol (median diameter: 0.26 μm) was successfully prepared using a beads-mill in water in the presence of a hydrophilic polymer and an anionic surfactant. The milled suspension was solidified with a sugar alcohol as a water-soluble carrier by spray-drying method. The co-precipitate was compressed into an immediate release tablet with common excipients. Oral bioavailability of the wet-milled cilostazol tablet in male beagle dogs was 13-fold higher than the hammer-milled commercial tablet in fasted condition. Food did not increase the oral bioavailability of the wet-milled tablet, while 4-fold increase was found for the commercial tablet. Irrespective to the bioavailability enhancement, in vitro dissolution rate of the wet-milled tablet was even slower than the commercial tablet by the compendial method (USP Apparatus 2). On the other hand, a good correlation was found between the dissolution profiles obtained by a flow-through cell method (USP Apparatus 4, closed-loop system without outlet filter) using a large volume of water and sodium lauryl sulfate (SLS) solution at the concentration lower than the critical micellar concentration (cmc) as dissolution media corresponding to the fasted and fed conditions, respectively.

Original languageEnglish
Pages (from-to)29-37
Number of pages9
JournalJournal of Controlled Release
Issue number1
Publication statusPublished - Aug 25 2008


  • Bioavailability
  • Cilostazol
  • Dissolution
  • Flow-through cell
  • Wet-milling

ASJC Scopus subject areas

  • Pharmaceutical Science


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