PAEDIATRIC RESPIRATORY REVIEWS (2004) 5(Suppl A), S103–S106
Inhaled corticosteroids:
devices and deposition
Bruce K. Rubin
Professor and Vice Chair for Research, Dept. of Pediatrics; Section Chief, Pediatric Pulmonary
Medicine; Professor of Biomedical Engineering, Physiology and Pharmacology, Wake Forest
University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1081, USA
INTRODUCTION
Inhaled corticosteroids (ICS) are the most effective
anti-inflammatory drugs used today for the preven-
tion and treatment of asthma in children. Recent
advances in aerosol delivery including improved
formulations of ICS and newer devices present the
clinician with an increasing variety of choices when
trying to decide what form of ICS therapy is best
suited to an individual patient. In this paper I will first
briefly review the physics and physiology of aerosol
generation and deposition followed by a discussion
of the potential advantages and disadvantages of
devices currently used.
AEROSOL PHYSICS
An aerosol is a group of particles that remains
suspended in air because of a low terminal settling
velocity. The terminal settling velocity of an aerosol
can be described as a function of aerosol size and
density; the mass median aerodynamic diameter
(MMAD) equal to the particle diameter multiplied
by the square root of particle density. The MMAD
normalises particle size to the behaviour of a
spherical droplet of water which by definition has
a density of 1. Because therapeutic aerosols are
never of uniform diameter, shape, or density, MMAD
is generally determined by physical methods which
can include laser light scattering, time of flight, or the
settling behaviour of aerosol particles on a series
of stages graded for size in either a multi-stage
liquid impinger or in a cascade (Anderson) impactor.
The three major mechanisms of aerosol deposition
are inertial impaction, gravitational sedimentation,
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and diffusion. Inertial impaction is the primary
mechanism for deposition of particles greater
than 4 mm MMAD. Large particles will fail to be
suspended for appreciable periods of time and
are more likely to settle within the device or on
the patient’s face or oral pharynx. Furthermore,
nose breathing will filter aerosol from inspired
gas. Impaction is also markedly increased by high
inspiratory flow as in children who are distressed or
crying.
Gravitational settlement describes the effects of
gravity on particles not influenced by inertia. This
is the primary deposition mechanism for particles
less that 2 mm MMAD and can affect larger particles
under low flow conditions. Diffusion affects extremely
small particles where Brownian motion has a greater
influence on particle movement than gravity. This
results in coalescence of particles within the airway
particularly when they are within a distance from
the airway wall of less than 25 times the particle
diameter.
Another important concept in understanding par-
ticle deposition in the lower airway is that of particle
size distribution. The MMAD will be the same if the
majority of particles are all of similar size or if there is
a huge size disparity of particles with a large number
of extremely small and extremely large particles
but a mass median diameter that is the same.
Clearly it is advantageous for a greater proportion
of the particles to be in the respirable fraction
(MMAD 0.5-5 mm). Size dispersion is measured
as the geometric standard deviation (GSD). By
definition, a monodisperse aerosol has a GSD less
than 1.22. Nearly all therapeutic aerosols can be
considered heterodisperse.
Particle composition will also influence the mass
of drug delivered to the airway in that particles
1526-0542/$ – see front matter © 2004 Elsevier Science Ltd. All rights reserved.