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at fl ow rates of 60 and 100 L/min, and models obtained were validated
using laser Doppler velocimetry techniques. Different mouthpiece
designs, cylindrical, conical, and oval, were analyzed. The authors found
pronounced infl uence of mouthpiece geometry on fl ow fi eld in the
mouthpiece, which affected the velocity of the exiting airfl ow. It was
shown that the axial component of the velocity vector, not the radial
component, controls the amount of throat deposition. It was demonstrated
that by minor changes in mouthpiece geometry, the amount of throat
deposition may be reduced.
Aerosolization in DPIs is based on the energy provided by the patient's
inspiration, and in order to achieve drug delivery to the respiratory tract,
particles need to have an aerodynamic diameter of approximately 1 to
5 µm. Particles within this size range have a high surface area, which
leads to high cohesive and adhesive forces, resulting in a poor
aerosolization effi ciency. Two common formulation approaches utilized
to overcome this problem are the carrier-based system and the
agglomeration-based system (Young et al., 2007). In the carrier-based
system, the micronized drug adheres to the larger carrier particle and
during inhalation separates from the carrier, after which it is inhaled into
the lungs, while the carrier particles are retained in the oropharynx. In
the agglomeration-based system, the micronized drug is agglomerated
with the micronized excipient, and during the patient's inhalation,
turbulence and collisions between agglomerates and the inhaler walls
break the agglomerates, and both drug and the excipient are inhaled into
the lungs.
Wong et al. (2011b) investigated the infl uence of the grid structure on
mechanisms of break-up and aerosolization in agglomeration-based DPI
systems. The authors designed various grids that differ in wire diameter
and aperture sizes, and applied CFD analysis to evaluate the infl uence of
impaction against a grid structure at different fl ow rates (60, 100, or
140 L/min) on agglomerate break-up and aerosolization effi ciency. It was
found that impaction against the grid structure is the prevalent break-up
mechanism when compared with turbulence generated by the grid. It was
shown that if the agglomerate passes through the center of the large grid
aperture without impacting upon the grid structure, it will encounter
minimal forces acting to break it up, because the turbulence kinetic
energy in the center of the grid aperture is small (Figure 7.7). If the
agglomerate impacts upon the grid, it will break into fragments that will
be re-entrained in close proximity to the edges, that is, into regions of
high integral shear and turbulence kinetic energy, which act to further
break up these fragments. It was also found that at higher fl ow rates,
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