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

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 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. 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.

journal_name

Pharm Res

journal_title

Pharmaceutical research

authors

McConville JT,Overhoff KA,Sinswat P,Vaughn JM,Frei BL,Burgess DS,Talbert RL,Peters JI,Johnston KP,Williams RO 3rd

doi

10.1007/s11095-006-9904-6

subject

Has Abstract

pub_date

2006-05-01 00:00:00

pages

901-11

issue

5

eissn

0724-8741

issn

1573-904X

journal_volume

23

pub_type

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