DEFINITION

Technically,

an aerosol is a suspension of fine

solid particles or liquid droplets in a gas.
Examples are smoke, oceanic haze and smog.
In general conversation, aerosol usually refers
to an aerosol spray can or the output of such a
can.
Pharmaceutical aerosols are Active
Pharmaceutical ingredients in solid or liquid
state suspended in a propellant.
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COMPOSITION OF IPA
Composition

of an aerosol inhaler is a follows;

an active material, a propellant containing a
hydrofluoroalkane (HFA), a cosolvent and
further low volatility component to increase the
mass median aerodynamic diameter (MMAD)
of the aerosol particles on actuation of the
inhaler, filling of an aerosol container and use
of the composition for the administration of
active materials by inhalation
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Inhaler Types
There

are many different inhalers used to

deliver IPAs.
MDI - The technical term for such puffers is
"pressurized metered dose inhaler" or
"propellant metered dose inhaler", usually
abbreviated as pMDI or simply MDI. A sketch
of a typical such device is shown below

MDPI

 pMDIs

are the most commonly used inhaler

worldwide, and have been used since the mid
1950s. The aerosol is created when a valve is
opened (usually by pressing down on the
propellant canister), allowing liquid propellant to
spray out of a canister, involving a complex
process called cavitation.
The drug is usually contained in small particles
(usually a few um in diameter) suspended in the
liquid propellant, but in some formulations the
drug is dissolved in the propellant.
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 In

either case, the propellant evaporates

rapidly as the aerosol leaves the device,
resulting in small drug particles that are
inhaled.
Prior to the mid 1990s, pMDIs used various
chlorofluorocarbons (CFCs) as their propellant,
but with the elimination of CFCs in industry due
to ozone depletion concerns, the propellants in
new pMDIs typically use hydrofluoroalkanes
(HFAs), which do not result in ozone depletion.
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 Add-on

devices (spacers, holding chambers

and other modifications) are sometimes used
with pMDIs (particularly in young children) to
remove the difficulty some patients have with
coordinating inhalation with firing the pMDI
spray.
Such add-on devices can also reduce the
amount of drug depositing in the mouth and
throat.
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NEBULIZERS
Although

pMDIs are the most common type

of modern day inhaler, they are not the
oldest. This honour goes to nebulizers, which
have been around in one form or another for
more than a century. Nebulizers produce a
mist of drug-containing water droplets for
inhalation. They are usually classified into
two types: electronic nebulizers and jet
nebulizers.
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 Jet

nebulizers are more common due to their

lower cost, and use a source of pressurized
air to blast a stream of air through a drugcontaining water reservoir, producing droplets
in a complex process involving a viscosityinduced surface instability that leads to
nonlinear phenomena in which surface
tension and droplet breakup on baffles play a
role. In contrast, electronic nebulizers
produce droplets by mechanical vibration of a
plate or mesh.
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 In

either type of nebulizer, the drug is usually

contained in solution in the water in the
nebulizer and so the droplets being produced
contain drug in solution. However, for some
formulations (notably Pulmicort) the drug is
contained in small particles suspended in the
water, which are then contained as particles
suspended inside the droplets being
produced. A schematic diagram of a typical
nebulizer is shown below.
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NEBULISER

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DPI
The

third major type of inhaler is the dry powder

inhaler, abbreviated as DPI.
In DPIs the aerosol is a powder, contained within
the device until it is inhaled. The therapeutic drug
is manufactured in powder form as small powder
particles (5 micrometers in diameter).
In many DPIs the drug is mixed with much larger
sugar particles (usually lactose monohydrate), that
are typically 50-100 micrometers in diameter.
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The much smaller drug particles attach to these

excipient particles. The increased aerodynamic
forces on the lactose/drug agglomerates improve
entrainment of the small drug particles upon
inhalation, in addition to allowing easier filling of
small individual powder doses. Upon inhalation, the
powder is broken up into its constituent particles
with the aid of turbulence and/or mechanical
devices such as screens or spinning surfaces on
which particle agglomerates impact, releasing the
small, individual drug powder particles into the air to
be inhaled into the lung. The sugar particles are
intended to be left behind in the device and in the
mouth-throat.
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 Although

pMDIs, DPIs and nebulizers are the

three major types of inhalers currently on the
market today, new inhaler designs are
continually being invented and several novel
designs are making their way through the
regulatory approval process, so that in the
future we may see inhalers that do not readily
classify into one of the three traditional
inhaler types mentioned above.
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The Importance of Particle Size

When

the lung is the target for the aerosol

(either because the intent is to treat the lung
surface or to get the drug into the blood
through the capillaries via the alveoli) the
inhaled aerosol must consist of particles in a
certain size range.( 1-5 micrometers in
diameter), This is because particles larger
than this size tend to simply land in the mouth
and throat and mostly do not make it into the
lung.
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 Particles

somewhat smaller than this size tend

to get inhaled and then exhaled right back out,
while very small particles usually can't be made
in high enough numbers to give high enough
dosages. Thus, IPAs are usually designed to
produce drug particles each having the
incredibly small mass of between approximately
1 and 100 ngm. For particles with densities near
that of water, this corresponds to particle
diameters of a few um .
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Some Challenges with Inhaled

Pharmaceutical Aerosols (IPAs)
1.

One of the main challenges with IPAs is

producing such small particles - a mass
between 1 and 100 trillionths of a gram in a
device that can be carried around easily!
Developed process is drug specific and so one
process for one particular drug will not work
well or not work at all, for a different drug.
Research and development process must be
revisited for each drug under consideration, a
time-consuming and labor intensive process.
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 2.

Another challenge is the fact that everyone

inhales differently. Thus, the speed of the air that
an inhaled pharmaceutical aerosol (IPA) is
exposed to is different for everyone. This presents
some interesting challenges.
For example, for certain dry powder inhalers, this
requires trying to design the powder so that
people inhaling either slowly or quickly both inhale
similar amounts of powder from the device.
Inhaled air speed can also affect where particles
deposit in the respiratory tract
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 3.

Another complicating factor is caused by

differences in the geometry of people's mouththroat airway passages, with some people
having very sudden bends that cause many
particles to deposit in the mouth-throat while
others have a relatively "smooth" mouth-throat
passage with much less mouth-throat
deposition. This can cause variability in the
dose reaching the lung between different
patients
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 4.

A further complication is added by the

differing effects of device mouthpieces on
mouth-throat geometry and their effect on the
fluid mechanics in the mouth-throat (small
diameter mouthpieces that have been
commonly used in the past have been shown
to cause high mouth-throat deposition due to
a high speed jet of air impacting in the
mouth). There are also differences in the lung
geometry between individuals.
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 5.

Finally, different disease states can also

result in differences in where IPAs deposit in
the lungs of different individuals.
6. For drug carried by inhaled water droplets
(such as are produced by nebulizers), the
humidity of the air being inhaled can cause
differing amounts of droplet evaporation and
also give rise to variations in where the drug
deposits in the lung.
These are just a few of the challenges that
need to be considered with IPAs.
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EXAMPLES OF IPA

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