Medical and Pharmaceutical Aerosols - Aerosols: Measurement, Dosimetry, and Health Effects - page 13

TABLE 1.3
Speciic Challenges of Particle Size Measurement of Pharmaceutical Aerosols

Device Manufacturer Trade Name Description of Atomization Mechanism References

Aerogen Aerodose ® Electrically induced vibrations to a concave surface generates

an aerosol from aqueous solution or suspension formulation

[203]

Aradigm AERx ® Computer-controlled device using a laser-machined nozzle

through which the formulation is mechanically extruded to
produce an aerosol

[204]
[205]

Battelle Mystic™ Electrohydrodynamic atomization [8]

Boehringer Ingelheim Respimat Mechanical propulsion [137]

ODEM TouchSpray™ Vibrating perforated membrane [206]

Source: Hickey, A.J. and Swift, D., Characterization of pharmaceutical and diagnostic aerosols, in: Baron, P.A. and
Willeke, K. eds., Aerosol Measurement: Principles, Techniques and Applications , Wiley, New York, pp. 1031-
1052, 2001.

is increased, while respirable particles are minimized. 138 In addition, systemically acting sprays
have been developed (NitroLingual™). This sublingual spray is used to deliver nitroglycerin for the
treatment of angina. A metered spray device is used. Topical sprays are also being investigated for
other systemically acting agents such as hormones. 139,140 Sinomenine hydrochloride has been deliv-
ered locally, for the treatment of rheumatoid arthritis, using a topical spray. 141 Related technologies
also include high-speed powder transdermal delivery (Powderject ® ). This involves the acceleration
of powder particles of a speciic size range, density, and strength so that they penetrate the skin
without the need for injections. Applications of this technology include traditional small-molecule
pharmaceutical agents, peptides, proteins, and vaccines. 142,143

1.4 SPECIFIC MEASUREMENT TECHNIQUES AND CALIBRATION
As with other aerosols, pharmaceutical and medical aerosols are described using properties such
as particle size, electrostatics, hygroscopicity, and uniformity of drug dispersion. 138 Measurement
is performed for product development and also for quality and regulatory purposes. Measurement
techniques focus on characterizing the eficiency and reproducibility by which aerosols are gener-
ated and delivered to the respiratory tract of patients. In vitro and in vivo techniques are used and
are summarized in the following.

1.4.1 P article s ize M easureMent
Particle size analysis is extremely important in the characterization of medical and pharmaceutical
aerosols as particle or droplet size and distribution are the most important physicochemical proper-
ties inluencing lung deposition. 144 Hence, the measurement of particle size is important in several
aspects of pharmaceutical aerosols, including particle manufacture, formulation optimization and
stability, and quality control. Medical and pharmaceutical aerosols are generally sized using two
general classes of particle size analysis: inertial methods and optical methods.
Particle size analysis in medical and pharmaceutical aerosols has unique issues relating to aero-
sol sampling. There are spatial restrictions between the generation site (device) and the inhalation
target site (lungs). The presence of inhalation low rates and cyclical breathing patterns in vivo also
complicates the interpretation of particle size observations. Measurement can be particularly chal-
lenging given the often unstable nature of generated particles due to evaporation, condensation,
temperature, and humidity changes.