title: Targeted high lung concentrations of itraconazole using nebulized dispersions in a murine model.
abstract: OBJECTIVE
  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 microm 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 microg/g (+/- SE) were achieved. Concentrations of up to 0.76 +/- 0.03 microg/g (+/- SE) could be maintained from the single nebulized dose for at least 24 h.
  
  
  CONCLUSIONS
  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.
authors.affiliation: College of Pharmacy, The University of Texas at Austin, Pharmaceutics PHR 4.214, 2409 W. University Avenue, Austin, Texas 78712-1074, USA. jtmcconville@mail.utexas.edu
authors.forename: Jason T
authors.initials: JT
authors.lastname: McConville
authors.forename: Kirk A
authors.initials: KA
authors.lastname: Overhoff
authors.forename: Prapasri
authors.initials: P
authors.lastname: Sinswat
authors.forename: Jason M
authors.initials: JM
authors.lastname: Vaughn
authors.forename: Bradi L
authors.initials: BL
authors.lastname: Frei
authors.forename: David S
authors.initials: DS
authors.lastname: Burgess
authors.forename: Robert L
authors.initials: RL
authors.lastname: Talbert
authors.forename: Jay I
authors.initials: JI
authors.lastname: Peters
authors.forename: Keith P
authors.initials: KP
authors.lastname: Johnston
authors.forename: Robert O
authors.initials: RO
authors.lastname: Williams
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002626:Chemistry, Pharmaceutical; D016503:Drug Delivery Systems; D017964:Itraconazole / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008168:Lung / Q000378:metabolism*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D053758:Nanoparticles; D009330:Nebulizers and Vaporizers; D012995:Solubility; D013499:Surface Properties; D013678:Technology, Pharmaceutical
chemical_list: D000935:Antifungal Agents; D017964:Itraconazole