Theoretical relationship of lung deposition to the fine particle fraction of inhalation aerosols

Abstract

Pharmaceutical inhalation aerosols intended to deliver drugs to the lungs may be sampled by inertial devices, that divide particle distributions into pre-calibrated diameters. A characteristic particle diameter (D50) is prescribed, below which the aerosol mass is designated the ‘respirable fraction’. The following studies compare designated respirable fractions with predicted lower lung deposition. Designated respirable fractions (% of particulate matter < 6.4 μm or alternatively < 9.8 μm) of 30, 40 and 50% were selected to represent typical inhalation aerosols. The compendial inertial samplers used to aerodynamically characterize the particle size of pharmaceutical aerosols operate at approximately 30 or 60 l/min. These values were selected as the volumetric flow rates (Qv) for a mathematical model of lung deposition. The model was employed to predict the lung deposition of particle size distributions giving rise to each designated respirable fraction. Nominal tidal volumes (TV) of 500 and 1622 ml were adopted at appropriate breathing frequencies to accommodate the designated Qv. Predicted lung depositions (± range due to particle size) of 1.4 ± 0.6%, at a respirable fraction of 30% (Qv = 60 l/min, Tv = 500 ml, D50 = 9.8 μm), and 20.9 ± 3.6%, at a respirable fraction of 50% (Qv = 30 l/min., Tv = 1622 ml, D50 = 6.4 μm) illustrate the range of results obtained. Under well defined conditions there appeared to be a qualitative correlation between respirable fraction and predicted lower lung deposition. However, this was influenced by the aerosol particle size distribution and breathing parameters.