• DOI:10.1208/s12249-012-9826-z
• Corpus ID: 16784193

Improved Bioavailability of a Water-Insoluble Drug by Inhalation of Drug-Containing Maltosyl-β-Cyclodextrin Microspheres Using a Four-Fluid Nozzle Spray Drier

@article{Ozeki2012ImprovedBO,
  title={Improved Bioavailability of a Water-Insoluble Drug by Inhalation of Drug-Containing Maltosyl-$\beta$-Cyclodextrin Microspheres Using a Four-Fluid Nozzle Spray Drier},
  author={Tetsuya Ozeki and Yoshihito Kano and Norimitsu Takahashi and Tatsuaki Tagami and Hiroaki Okada},
  journal={AAPS PharmSciTech},
  year={2012},
  volume={13},
  pages={1130-1137}
}

• T. Ozeki, Y. Kano, +2 authors H. Okada
• Published 1 September 2012
• Chemistry, Biology
• AAPS PharmSciTech

We previously developed a unique four-fluid nozzle spray drier that can produce water-soluble microspheres containing water-insoluble drug nanoparticles in one step without any common solvent between the water-insoluble drug and water-soluble carrier. In the present study, we focused on maltosyl-β-cyclodextrin (malt-β-CD) as a new water-soluble carrier and it was investigated whether drug/malt-β-CD microspheres could improve the bioavailability compared with our previously reported drug/mannitol (MAN) microspheres. The physicochemical properties of bare drug microparticles (ONO-2921, a model water-insoluble drug), drug/MAN microspheres, and drug/malt-β-CD microspheres were evaluated. In vitro aerosol performance, in vitro dissolution rate, and the blood concentration profiles after intratracheal administration were compared between these formulations. The mean diameter of both drug/MAN and drug/malt-β-CD microspheres was approximately 3–5 μm and both exhibited high aerosol performance (>20% in stages 2–7), but drug/malt-β-CD microspheres had superior release properties. Drug/malt-β-CD microspheres dissolved in an aqueous phase within 2 min, while drug/MAN microspheres failed to dissolve in 30 min. Inhalation of drug/malt-β-CD microspheres enhanced the area under the curve of the blood concentration curve by 15.9-fold than that of bare drug microparticles and by 6.1-fold than that of drug/MAN microspheres. Absolute bioavailability (pulmonary/intravenous route) of drug/malt-β-CD microspheres was also much higher (42%) than that of drug/MAN microspheres (6.9%). These results indicate that drug/malt-β-CD microspheres prepared by our four-fluid nozzle spray drier can improve drug solubility and pulmonary delivery.