Targeting aerosolized drugs to the conducting airways using very large particles and extremely slow inhalations

The site of deposition in the respiratory tract for aerosolized, inhaled therapeutic drugs depends on both the particles' aerodynamic size and the patient's breathing pattern.

In 21 healthy subjects with normal lung function, we evaluated an extremely slow inhalation of a large 9.5-μm MMAD particle aerosol (ESI-9) for its ability to enhance the delivery of radiolabeled particles ((99m)Tc-labeled sulfur colloid) to the conducting airways. The regional deposition of the large particles (modified Pari-Boy jet nebulizer), inhaled at the extremely low rate of 0.080 Lps for 10 sec, was compared to the deposition of 5-μm MMAD particles inhaled during cyclic resting tidal breathing (TVB-5-) (mean 0.44 L and 0.46 Lps). Gamma scintigraphy gave an estimate of conducting airway deposition (% CAD) as a fraction of all deposited particles by multiplying the percent of activity in both lungs immediately postdeposition relative to the total deposition (i.e., lungs + mouth + esophagus + stomach) times the percent of activity cleared from the lungs over 24 h.

% CAD for healthy subjects for the ESI-9 and TVB-5 maneuvers was 35% (±8%) and 27% (±11%), respectively, p = 0.004). The amount deposited within the oropharynx was 26% (±7%) and 37% (±11%), respectively, p < 0.001.

Higher therapeutic value of a medication delivered to the conducting airways where the primary defect is associated with many diseases, and with fewer losses to the extrathoracic surfaces, may be obtained by using an "extremely slow inhalation and large particle" routine when compared to a normal tidal volume breathing associated with typical nebulizers.