Factors affecting the deposition of inhaled porous drug particles

Recent findings indicate that the inhalation of large manufactured porous particles may be particularly effective for drug delivery. In this study, a mathematical model was employed to systematically investigate the effects of particle size, particle density, aerosol polydispersity, and patient ventilatory parameters on deposition patterns of inhaled drugs in healthy human lungs. Aerodynamically similar particles with densities of 0.1, 1.0, and 2.0 g/cm(3) were considered. Particle size distributions were defined with mass median aerodynamic diameters (MMADs) ranging from 1 to 3 microm and geometric standard deviations ranging from 1.5 to 2.5, representing particles in the respirable size range. Breathing rates of 30 and 60 L/min with tidal volumes of 500 to 3000 mL were assumed, simulating shallow to deep breaths from a dry powder inhaler. Particles with a high density and a small geometric diameter had slightly greater deposition fractions than particles that were aerodynamically similar, but had lower density and larger geometric size (typical of manufactured porous particles). This can be explained by the fact that particles with a small geometric diameter deposit primarily by diffusion, which is a function of geometric size but is independent of density. As MMAD increased, the effect of density on deposition was less pronounced because of the decreased efficiency of diffusion for large particles. These data suggest that polydisperse aerosols containing a significant proportion of submicron particles will deposit in the pulmonary airways with greater efficiency than aerodynamically similar aerosols comprised of geometrically larger porous particles.