Medical and Pharmaceutical Aerosols - Aerosols: Measurement, Dosimetry, and Health Effects - page 17

low-pressure impactor (BLPI) to create an electrical low-pressure impactor (ELPI), 175 or modifying
a Next Generation Impactor (NGI) to create an Electrical Next Generation Impactor (eNGI). 176,177
These apparatus allow the elucidation of triboelectriication as a function of particle size, and these
data can be used both in the design of an inhaler or the formulation of the drug.

1.5 RESPIRATORY DEPOSITION, RETENTION, AND DOSIMETRY

1.5.1 d ePosition
1.5.1.1 Gamma Scintigraphy, PET, and SPECT
The assessment of lung deposition of pharmaceutical and medical drug delivery systems is a key
step in the evaluation of pharmaceutical aerosol device performance. It has also been shown that
with inhaled anti-asthma drugs, lung deposition data can act as a surrogate for clinical response.
Thus, lung deposition studies can facilitate optimized drug delivery to the lungs during product
development and also can be used in therapeutic equivalency studies. Gamma scintigraphy has been
widely used in quantifying regional lung deposition of aerosolized drugs. 178 Gamma scintigraphy is
a planar imaging technique where a gamma-ray-emitting nuclide of appropriate half-life (typically
99 m Technetium for pulmonary systems) is included in the pharmaceutical formulation such that
its aerodynamic particle size and deposition parallels that of the drug substance. The radionuclide
distribution in the lungs is then analyzed using a gamma camera and can be quantiied using com-
puter-based software. Single-photon emission computed tomography (SPECT) is similar to gamma
scintigraphy in that it involves similar radio-labeling procedures and measurement of deposition
using a gamma camera. 179 However, in SPECT the emitted gamma rays are detected using a rotating
gamma camera from various angles in order to obtain several views of lung deposition. Thus, it may
be possible to deine drug deposition more closely with respect to the three-dimensional anatomy
of the lung. Nebulizers and MDIs have been investigated using this technique, but some signiicant
drawbacks are that larger amounts of radionuclides are required for satisfactory scintigraphic data
collection and that longer imaging periods result in drug clearance from the lung. 179 Positron emis-
sion tomography (PET) is a relatively new technique in analyzing lung deposition resulting from
pharmaceutical systems. 179,180 The basis of the method is the use of positron emitting nuclides (typi-
cally 11C, 15O, 13N, or 18F) that are detected after positron collision with electrons. This interac-
tion results in two photons being emitted in opposite directions that are detected using coincident
counting of photons on ring-shaped array of detector elements. Advantages of the technique include
the small radiation doses resulting from the relatively short half-lives of the radionuclides used,
scanning times are very short, picomolar concentrations of nuclides are detectable, and nuclides are
often chemically incorporated into the drug molecule rather than physical attachment. 179 However,
these are balanced against practical disadvantages of handling radionuclides with such short half-
lives: transportation, formulation and labeling steps, and dosing volunteers. Apart from time limi-
tations the cost of PET can also be signiicant due to the need for a nearby cyclotron and detector
equipment. These factors need to be weighed against the PET images that yield more precise rela-
tion of deposition data with three-dimensional structural features of the respiratory tract. 179

1.5.2 r etention
The retention of aerosols in the lungs is related to the physicochemical properties of the material,
particularly those linked to dissolution rate, 181,182 and the mechanisms of clearance from the lungs,
that is, absorption, mucociliary transport, and cell-mediated transport. 183
Rapidly dissolving particles are subject to clearance from lungs by absorption and mucociliary
clearance depending on the site of deposition. Slowly dissolving particles are cleared predominantly
by mucociliary clearance in the upper airways and macrophage uptake in the periphery of the lungs.