Targeted high lung concentrations of itraconazole using nebulized dispersions in a murine model

Jason T. McConville, Kirk A. Overhoff, Prapasri Sinswat, Jason M. Vaughn, Bradi L. Frei, David S. Burgess, Robert L. Talbert, Jay I. Peters, Keith P. Johnston, Robert O. Williams

Research output: Contribution to journalArticle

54 Scopus citations

Abstract

Purpose. The purpose of this study was to investigate the delivery of itraconazole (ITZ) particles to a murine lung model by nebulization. Methods. Three ITZ formulations were prepared and characterized in the dry state using contact angle, dissolution, X-ray powder diffraction, scanning electron microscopy, and Brunauer-Emmett-Teller surface area analysis. Aerodynamic particle size distributions and lung deposition studies in 14 outbred male ICR mice were performed using aqueous dispersions of all the formulations. A separate dosing uniformity study was also performed to qualify use of the chamber. Results. All formulations had an aggregated particle size of approximately 30 μm in diameter. Two formulations showed that 80% of the drug dissolved in less than 5 min. The remaining ITZ formulation had a slower dissolution and the lowest total emitted dose from the nebulizer used. High concentrations of ITZ were shown to be present in the mouse lung during the lung deposition study, up to 16.8 ± 0.13 μg/g (± SE) were achieved. Concentrations of up to 0.76 ± 0.03 μg/g (± SE) could be maintained from the single nebulized dose for at least 24 h. Conclusion. An effective method of targeted delivery of ITZ to the deep lung is presented that may be useful for the treatment and prevention of acute fungal infections.

Original languageEnglish (US)
Pages (from-to)901-911
Number of pages11
JournalPharmaceutical Research
Volume23
Issue number5
DOIs
StatePublished - May 1 2006

Keywords

  • Antifungal
  • Fungal infection
  • Nanoparticle
  • Nebulization
  • Poorly water-soluble

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)

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    McConville, J. T., Overhoff, K. A., Sinswat, P., Vaughn, J. M., Frei, B. L., Burgess, D. S., Talbert, R. L., Peters, J. I., Johnston, K. P., & Williams, R. O. (2006). Targeted high lung concentrations of itraconazole using nebulized dispersions in a murine model. Pharmaceutical Research, 23(5), 901-911. https://doi.org/10.1007/s11095-006-9904-6