The treatment of pulmonary infectious diseases with pharmaceutical aerosols is an attractive
option considering the accessibility of the lungs for topical drug delivery. Aerosols have been
targeted to the lungs for the treatment of asthma with great success. Current therapies for
other diseases, including Pseudomonas aeruginosa, Pneumocystis jirovecii (formerly Pneumocystis
carinii), and mycobacterial infections, remain suboptimal due to the efficacy/safety profile.
This may be improved by aerosol targeted pulmonary drug delivery. Azithromycin is a
broad spectrum antibiotic that acts by inhibiting protein synthesis. It is associated with side
effects that might be avoided by aerosol delivery to the lungs. In the present study three concentrations
of azithromycin (10, 50, and 100 mg/mL) were delivered from three nebulizers
(Acorn II, Updraft, and LC Plus) operated at 8 L/min. Particles size analyses were conducted
by inertial impaction and laser diffraction. In addition, emitted doses were determined. A linear
proportionality existed across the concentration range between nominal dose and both
fine particle dose/fraction and emitted dose, with R
2 > 0.999 in all cases. The mass median
aerodynamic diameter increased from 1.4 to 1.9 µm between 10 and 100 mg/mL of azithromycin
solution concentration for the Acorn II. The particle size distributions were not all log-normally
distributed. The median particle size delivered from the devices was largest for the Updraft
(2.8 µm) and smallest for the Acorn II (1.9 µm) for 100 mg/mL azithromycin solution concentrations.
The efficiencies of small particle delivery (%<4.7 µm) were as follows, LC Plus =
Acorn II (85%) > UpDraft (75%). However, the emitted dose from the LC Plus (55 mg/min) was
higher than the Acorn II (31 mg/min) to maximize lung exposure to the aerosol, small median
diameters and broad particle size distributions would be most effective. This study demonstrates
that the dose delivered to the lungs will be maximized, under the current operating
conditions by adopting the LC Plus, and high (100 mg/mL) azithromycin concentrations.
