Targeted high lung concentrations of itraconazole using nebulized dispersions in a murine model.
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.
McConville
Jason T
JT
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
Overhoff
Kirk A
KA
Sinswat
Prapasri
P
Vaughn
Jason M
JM
Frei
Bradi L
BL
Burgess
David S
DS
Talbert
Robert L
RL
Peters
Jay I
JI
Johnston
Keith P
KP
Williams
Robert O
RO
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
D000935:Antifungal Agents; D017964:Itraconazole