PHARMACEUTICAL

AEROSOL
DEFINITION
"An aerosol is a disperse phase system, in which
very fine solid drug particles or liquid droplets
get dispersed in the propellants (gas), which
acts as continuous phase".
OR
"An Aerosol system which expels the contents
from the container that depends on the
pressure development by compressed or
liquefied gas" 
“ An aerosol is a pressurized dosage forms
containing one or more therapeutic active
ingredients which upon actuation emit a fine
dispersion of liquid and/or solid materials in a
gaseous medium contain smaller than 50 um".
• An Aerosol also called as Pressurized Packages,
Pressure Package or Pressurized dosage forms.
• The term pressurized package is generally used
when referring to the aerosol container or a
complete product. Pressure is developed to the
aerosol system through the use of one or more
liquefied or gaseous propellants.
 Advantages of aerosol
1. Medication is dispensed in a ready to use form at the
push of a buttom.
2. A portion of a medication may be easily withdrawn
w/o contamination
3. Topical medication may be applied in a uniform, thin
layer to the skin w/o touching the affected area.
4. Aerosol container protects drug adversely affected by
light.
5. Aerosol application is clean process, requiring little or
no wash-up by the user.
Components of Aerosol Package
• The following components / parts require for
aerosol product:
1) Propellant
2) Product concentrate
3) Container
4) Valve and Actuator
Propellants
• Propellants are responsible for developing the
pressure in the aerosol container and also it
expel the product from the container when
the valve is opened and helps in expelling the
product by atomization of contents or by
causing foam production of the product.
• When the propellant/s is a liquefied gas or a
mixture of liquefied gases, it frequently serves
the propellant and solvent or vehicle for the
product concentrate.
Types of propellant
• Depending on the route of administration and
use, the propellant can be classified as
I) Type-I Propellant: A- Liquified Gas
II) Type-II Propellant: B - Compressed Gas
I) Type-I Propellant
A- Liquified Gas:
1) For oral and inhalation (Fluorinated hydrocarbons):
• Tri-chloro-mono-flouro methane (propellant 11)
• Di-chloro di-fluro methane (propellant 12)
• Di-chloro tetra-fluro ethane (propellant 114)
2) Topical Pharmaceutical aerosols (Hydrocarbons):
• Propane
• Butane
• Isobutane
II) Type-II Propellant 
B - Compressed Gas Propellants
 Compound gases:
• Nitrogen
• Carbon di-oxide
• Nitrous oxide
Difference between Liquefied Propellant and
Compressed Gas Propellant
AEROSOL CONTAINERS
• They must be stand at pressure as high as 140 to
180 psig (pounds per sq. inch gauge) at 130 F.
• The glass or metal containers are generally used.
Glass disadvantage is brittleness, so restricted
usage of glass.
• If the pressure is less than 25 psig and propellant
content is less than 15% then glass can be used.
• It should be coated with plastic coating in two
layers if pressure is less than or equal to 33 psig.
For linings Epoxy and vinyl resins can be used.
• The only true tamper resistant packaging is the
aerosol containers
• Different types of materials for aerosol
containers are:
1) Metals
- Tin plated steel (Side-seam or Three, Two piece
or Drawn, Tin-free steel)
- Aluminum
- Stainless steel
2) Glass
- Uncoated glass
- Plastic coated glass
3) Plastics
• Following types of actuators available.
a) Spray actuators: These are having capable of
dispersing the stream of product concentrate
and propellant into relatively small particles by
allowing the stream to pass through various
openings 0.016 to 0.040 inches. It breaks
stream into fine particles.
• These actuators used for topical use such as
spray-on bandages, antiseptics, local
anesthetics and foot preparations.
b) Foam actuators: It consists of relatively large
orifices ranges from 0.070 to 0.125 inches.
c) Solid steam actuators: Similar to foam type of
actuators. Used for semisolid products like
ointments.
d) Special/ Mist actuators: These are designed
for special purpose, to deliver the contents of
medicaments at site of action like throat, eye
or vaginal tract.
Valve and Valve Assembly
• Valves deliver the drug in desired form and
regulate the flow of product concentrate from
the container.
• The valve should be able to withstand the
pressure encountered by product concentrate
and the container, should be corrosion resistant.
• They also provide proper amount of medication.
• Dispersing of potent medication at proper
dispersion/ spray approximately 50 to 150 mg±
10 % of liquid materials at one time use of same
valve.
• There are two types of valves available 
a) Continuous spray valve and 
b) Metering valve.
a) Continuous spray valves: To deliver the contents
in spray or foam or solid stream continuously
with or without measuring. These types of valves
are used for all types of pharmaceutical aerosols.
b) Metering valves: For potent medication and
exact amount of medicament will be dispensed at
one time application. Approximately 50 to 150
mg +- 10% at one time application.
Valve Assembly and its components
• Actuator
• Valve stem
• Gasket
• Valve Spring
• Ferrule/Mounting cup/Valve cup
• Valve Body/ Housing
• Dip tube
 Principle / Mechanism and working of Aerosols  
• For semi solid aerosol, the formulation is
similar to other semisolid preparation but
depends on nitrogen gas to that contents from
package.
 Classification of Aerosols
• Aerosols may be classified as
1) Space Sprays: 
These are finely divided sprays having particle size up to 50
um. E.g. Insecticides, Disinfectants and Room Deodorants etc.
2) Surface Coats: 
These are also sprays but disperse phase particles are coarse
with sizes up to 200 um. They produce a wet coat when
sprayed on a surface. E.g. Hair sprays, Powder sprays and
topical medicament sprays.
3) Foam: 
These are produced by rapid expansion of propellants through
an emulsion. Hence product comes out in the form of a foam
or froth. E.g. Shaving cream and vaginal cream.
Types of Aerosol Systems

1) Solution system / Two Phase system

2) Water based system / Two components or
Three components system
3) Suspension / Dispersion system
4) Foam system / Emulsion systems
5) Aqueous stable foams
6) Non-Aqueous stable foams
7) Quick Breaking foams
8) Thermal Foams
9) Intra Nasal Aerosols
10) Compressed Gas Systems
Solution system / Two Phase system:  (Vapour +
Liquid phase)
• Solution Aerosols are two phase systems
consisting of the product concentrate in a
propellant or mixture of propellants or a mixture
of propellant and solvent. Some solvents may also
be added to the formulation to retard the
evaporation of the propellant.
• Solution aerosols can be difficult to formulate
because many propellant or propellant-solvent
mixtures are non polar in nature and these are
poor solvents for the aerosol product concentrate.
Water based system / Two components or
Three components system : (Propellant +
Water + Vapour phase)
• Large amount of water can be used to replace all or
part of the non aqueous solvents used in aerosols.
• This system is composed of a layer of water
immiscible liquid propellant, highly aqueous product
concentrate and the vapour phase. This type of
system employed when the product is immiscible
with the propellant.
• This system emits the contents as spray or foam.
Spray is dispersion of active ingredient and other
solvents in an emulsion system, in this emulsion
system propellant as external phase.
Suspension Aerosols
• Suspension Aerosols can prepare, when the
product concentrate is insoluble in the
propellant or mixture of propellant and
solvent or when a co-solvent is not desirable. 
E.g: Anti-asthmatic drugs, steroids and
antibiotics are prepared in suspension
aerosols.
Foam system / Emulsion systems
• Emulsion or foam aerosols consist of Active
ingredient + Aqueous or Non aqueous vehicle
+ Surfactant + and propellant (Hydrocarbon or
compressed gases).
• Here the propellant which is present in the
liquid acts as internal phase.
• These aerosols dispensed as stable aqueous or
non aqueous or quick breaking foam aerosol.
Aqueous stable foams
• This system consists of propellant in the range
of 8 to 10% v/v. As the concentration of A-70,
A-46 propellant increases, it results in stiff and
drier spray. And wetter spray is produced as
the concentration of propellant decreases.
• Both Hydrocarbon and Compressed gases
used as propellants.
• This is generally used for steroids and
antibiotics.
Quick Breaking foams
• Here propellant is the external phase. When
dispensed, the product will emitted as foam
which soon collapses or merges in to liquid.
• Hence, this type of system can be applied to
small area or larger surface topical medication
without mechanical application.
• Here Cationic or anionic or non-ionic types of
surfactants are used in the formulation. It should
soluble in both alcohol and water.
• This is pressurized by mixing of 90% concentrate
and 10% propellant.
• Thermal Foams
• These are not using these days. Generally
thermal foams used when the warmness is
required.
• To produce warm foam for shaving.
• Not readily accepted by the consumer, so
discontinued due to expense and lack of
effectiveness.
Intra Nasal Aerosols
• Drug delivery systems intended for the deposition of
medication into the nasal pathways for effectiveness to
produce local or systemic effect.
• Intranasal preparations are limited to nasal drops, non
pressurized nasal sprays (mists), inhalants and intranasal
gels (jellies), ointments and creams. A new alternative is
Pressurized metered nasal aerosol.
• The design of the adaptor varies from the inhalation
aerosols. To produce smaller particles, the adaptors will
be of less height and narrow.
• These are free from contamination, very less quantity of
drug moves into the lungs, the mucosal irritation will be
reduced.
 Inhalers
• Inhalation dosage forms are the form of drugs
or solutions of drugs administered through the
(nasal or oral) respiratory route. Inhalers used
for local action on the bronchial tree or for the
systemic effects through absorption from the
lungs.
• Depending on the physical state of the
dispersed phase and continuous phase,
inhalation system of drug is classified into
three types:
A. Pressurized metered dose inhalers (pMDIs)
B. Dry powder inhalers (DPIs)
C. Nebulizers
A. Pressurized Metered dose inhaler (pMDIs)
The pressurized metered dose inhalers (pMDIs) consist of a
canister, actuator and a spacer. The canister is composed of
a metering dose valve with an actuating stem. The
formulation (containing the active ingredient i.e. drug, a
liquefied gas propellant and a stabilizer) is present in the
canister. The drug may be suspended or dissolved in the
liquefied gas propellant. Upon actuation, the metering dose
valve is opened which releases a single metered dose of
medication along with the liquified gas propellant to spray
out of a canister. This process is called "cavitation". The
liquefied gas propellant is volatile in nature, which breaks
down into liquid droplets and evaporates rapidly and the
dried micronized drug are inhaled to the lung.
Dry powder inhalers (DPIs)
• The DPIs are very advantageous than pMDIs.
Because
a) DPIs requires no coordination of actuation and
inhalation. It activated by patient's inspiratory airflow.
b) DPIs do not extract organic compounds from the device
components and the chances of degradation is less than
pMDIs.
c) The rate of drug release / delivery is good than pMDIs.
d) These are efficient, more stable and easier to use than
pMDIs.
Nebulizers
• Nebulizer is a device used to administer
medication in the form of a mist inhaled
through the lungs. Nebulizers use oxygen,
compressed air or ultrasonic power to break
up medical solutions and suspensions into
small aerosol droplets called mists that can be
directly inhaled from the mouthpiece of the
device. It produces a mist of drug containing
water droplets for inhalation purpose. The
powdered drug is present either in solution
form or suspension form in the nebulizer.
Advantages of nebulizers Disadvantages of nebulizer
• Patient coordination not • They are expensive.
required. • Electrical power or battery sources
• Effective with tidal are required.
breathing. • Jet nebulizer requires pressurized
• High dose possible. form of gas.
• No chlorofluorocarbon • The frequent cleaning required.
(CFC) is released. • There is a chance of contamination.
• Nebulizers used with • The suspension of dosage cannot
supplemental oxygen. be properly aerosolized.
• Can use for combination • The jet nebulizer produces large
therapy if compatible. and different sizes of particles.
• The ultrasonic nebulizer • The ultrasonic stimulation and rise
is faster in delivery, in temperature may cause
smaller and portable. degradation of drug.
FILLING OF AEROSOLS
• The manufactured aerosols can be filled in to
the containers can be done by following
methods and apparatus used.
a) Cold filling Apparatus
b) Pressure filling apparatus
c) Compressed gas filling apparatus
d) Rotary filling machine
General Formulation and Manufacturing
components of Aerosols
Evaluation of Aerosols

Pharmaceutical aerosols can be evaluated by testing

physicochemical, performance and biological tests.
1) Flammability and Combustibility
A) Flame Projection and flash back 
B) Flash Point
2) Physicochemical Characteristics
A) Vapour Pressure
B) Density
C) Moisture Content
D) Identification of Propellant
E) Concentrate - Propellant ratio
3) Performance Test
A) Aerosol Valve Discharge Rate
B) Spray Patterns
C) Dose Uniformity / Dosage Testing with Metered
valves
D) Net Contents
E) Foam stability
F) Particle Size determination
G) Leakage Test
4) Biological Testing
A) Therapeutic Activity
B) Toxicity
C) Extractable substances
 Packaging, Labeling and Storage
• A unique aspect of pharmaceutical aerosols compared to other dosage forms is
that the product is actually packaged as part of the manufacturing process. The
product is completely manufactured before itself and then placed in the
appropriate container.
• Most aerosol products have a protective cap or cover that fits snugly over the
valve and mounting cup. This mounting cap protects the valve against
contamination with dust and dirt. The mounting cap, which is generally made
of plastic or metal and also serves a decorative function.
• Exposure to temperatures above 49C may burst an aerosol container.
• When the canisters are cold (less than the usual results into spray). This may
be particularly important to users of metered-dose inhalation sprays.
• Storage 15C – 30C.

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