6.

Pharmaceutical Aerosols
Berhanemeskel W.G, Asst. Prof.
Department of Pharmaceutics
School of Pharmacy
College of Medicine and Health Sciences
University of Gondar

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Wednesday, October 01,
2014
Presentation Outline
Introduction
Components of aerosol Package
Stability testing
Equipment used
Quality control
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Introduction
Definition: A suspension of small solid particles or
droplets suspended in a gas or vapor.
Aerosol or pressurized package is a system that
depends on the power of a compressed or
liquefied gas to expel the contents from the
container
Pressurized packages existed during the early
1900s
Aerosol industry begin in 1942, aerosol insecticide
developed by Good hue and Sullivan of the US
Department of Agriculture.
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The principle of aerosol technology were
applied to the development of pharmaceutical
aerosols in the early 1950s
In 1950s- intended for topical administration
In 1955- intended for local activity in the
respiratory tract
Introduction (2)
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Advantages of Pharmaceutical
Aerosols
Dose can be removed without contamination
of remaining material
Medication can be delivered directly to the
affected area in a desired form
Irritation produced by the mechanical
application of topical medication is reduced or
eliminated
Ease and convenience of application and
application of medication in thin layer
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Limitations
Expensive
Performance of package can deteriorate
during life of product
Limited safety hazard
Flammable
Pressurized
Inadvertent inhalation
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Types of drug delivery systems
Nebulizers
used to administer medication to people in the form of a
mist inhaled into the lungs.
Meter dose Inhaler (MDI)
are pressurized, hand-held devices that use propellants to
deliver doses of medication to the lungs of a patient
Propellant driven
Aqueous pump sprays
Dry powder inhaler (DPI)
delivers medication to the lungs in the form of a dry
powder.
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Components of Aerosol Package
An aerosol product consists of the
following component parts:
1. Propellant
2. Container
3. Valve and actuator (Button)
4. Product concentrate

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Propellant
It is responsible for developing the proper pressure within the
container
It expels the product when the valve is opened and aids in the
atomization or foam production of the product
Types of Propellant
1. Fluorinated hydrocarbons e.g.
Trichloromonfluoromethane (Prop 11)
Dichlorodifluoromethane (Prop 12)
Dichlorotetrafluoroethane (Prop 114)
2. Hydrocarbons e.g.
Propane, Butane, and Isobutane
3. Compressed gases e.g.
Nitrogen, Carbon dioxide, and Nitrous oxide
4. Hydrofluoroalkanes
In practice blends are used to provide various vapor pressure. The
ultimate interest is to have vapor pressure
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Hydrocarbon Propellants
Advantages
Inexpensive
Minimal ozone depletion
Negligible greenhouse effect
Excellent solvents
Disadvantages
Flammable
Aftertaste
Unknown toxicity following inhalation
Low liquid density

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Chlorofluorcarbons (Used only in
inhalation aerosols)
Advantages
Low inhalation toxicity
High chemical stability
High purity
CFC-11 is a good solvent
Disadvantages
Destructive to atmospheric Ozone
Contribute to greenhouse effect
High cost
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Hydrofluoroalkanes (aka
Hydrofluorocarbons)
Advantages
Low inhalation toxicity
High chemical stability
High purity
Not ozone depleting
Disadvantages
Poor solvents
Minor greenhouse effect
High cost
e.g. 1,1,1,2,3,3,3 Heptafluoropropane (HFA-227), 1,1,1,2 Tetrafluoroethane
(HFA-134a)

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Compressed gas propellants
Advantages
Low inhalation toxicity
High chemical stability
High purity
Inexpensive
No environmental problems
Disadvantages
Require use of a nonvolatile co-solvent
Produce course droplet sprays
Pressure falls during use
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Containers
Containers must withstand pressure as high as
140 to 180 psig
Types of containers:
1. Tin plate containers
consists of sheet of steel plate that has been
electroplated on both sides with tin
2. Aluminum containers
greater resistance to corrosion
Light weight, not fragile
Good for light sensitive drugs
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3. Stainless steel container
Limited for smaller size
Extremely strong and resistant to most materials
Pressure stand
4. Glass containers
Available with plastic or without plastic coating
Compatible with many additives
No corrosion problems
Can have various shape because of molding
Fragile
Not for light sensitive drugs
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Valves
Deliver the content in the desired form
Generally designed to work in inverted position
Primary function reproducibly delivery an aliquot
of liquid phase in which drug is dissolved or
suspended
There are mainly two types of valves
Continuous spray valve
Metering valves
Has various components:
Mount cap, Valve housing, Stem, Gasket
(rubber), Spring, Deep tube
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Are specially designed buttons
Ensure proper delivery of the aerosols by
allowing the opening and closing of the valve
When actuators depressed valve open
They produce different forms of final product
Actuators
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Formulations
Pharmaceutical aerosol
Product concentrate + Propellant
Filling first product concentrate to the
container and then fill propellant during
package = two steps
Product concentrate is composed of
Active ingredients
Solvent
Additives
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Types of systems
1. Solution system
Consist of two phases liquid and vapor
If the active ingredient is soluble in propellant
it has one system
The ratio of propellant and solvent could
range from 5% (foaming) to 95% (inhalation).
To lower vapor pressure we can add solvents
of non volatile e.g. Propylene glycol, acetone,
alcohol
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2. Water based systems
Are increasing in use nowadays
Have relatively large amount of water
There is three phase system: water, propellant and vapor
In aquasol system it has two phases i.e. water and vapor
3. Dispersed systems (suspension)
It needs surfactants
Particle size is important
4. Foam systems
Have foaming agent
Aqueous or non aqueous
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Stability testing
Stability is tested during the product development
Parameters for product concentrate and propellant are:
Vapor pressure - Spray rate (pattern valve)
pH - Specific gravity
Viscosity - Total weight with time
Purity of propellant
Total weight of active ingredient with time
Color and odor
Containers stability
Pressure withstand
Corrosion
Stability of valves and actuators functions
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Equipments used
Those fill at pressurized and low temperature
1. Pressure filling (gauge-burette)
2. Cold filling (low temp.)
3. Compressed gas filling (after concentrate has
been filled)
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Quality control (QC)
Leak test
Passing the filled container to hot water. If there is
bubble it has leak
Q.C on propellant
Q.C on concentrate and their stability
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