This is a seminar of my M Pharm Sem-II. It consist of nearly all information about the dosage form called Aerosol in briefly. It will be helpful for the students to get insights about this topic in very simple manner.

1. 7/01/2021 1
AEROSOLS, PROPELLANTS,
CONTAINERS TYPES,
PREPARAION AND EVALUATION
Guided By :
Dr. L. R. Zawar
(HOD, Dept. of Pharmaceutics)
DEPT.OF PHARMACEUTICS/HRPIPER ,SHIRPUR
Presented By:
Gaurav Shriram Patil
M Pharm I Year (SEM II)
H.R. PATEL INSTITUTE OF PHARMACEUTICAL EDUCATION AND RESEARCH ,SHIRPUR (MH)

2. I. INTRODUCTION
II. COMPONENTS OFAEROSOL PACKAGE
III. TYPES OF SYSTEM
IV. MANUFACTURING OF PHARMACEUTICAL
AEROSOLS
V. QUALITY CONTROL OF PHARMACEUTICAL
AEROSOLS PACKAGE
VI. EVALUATION TESTS OF PHARMACEUTICAL
AEROSOLS
VII. NEWER DEVELOPMENTS
VIII. REFERENCES
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CONTENTS

3. DEFINITION – PHARMACEUTICAL AEROSOLS
• Pharmaceutical aerosols are the products that are packed under
pressure and contain therapeutically active ingredient that
releaseupon activationof appropriatevalve system.
• A system that depends on the power of a compressed to expel
the contentsfrom the container.
• Development of pharmaceutical aerosolsis occurred in 1950s.
• These aerosol products were intended for burns , minor cuts and
bruises , infections and various dermatologic conditions.
• Aerosol products intended for local activity in the respiratory
tract appeared in 1955 , when Epinephrine was made available
in a pressurized package.
I INTRODUCTION
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4. An aerosol
product
consist of
following
component
parts :
Propellant
Container
V
alve and actuator
Product
concentrate
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II COMPONENTS OF AEROSOL PACKAGE

5. The propellant is responsible for developing the
proper pressure within the container
• The propellant is responsible for developing the
proper pressure within the container.
• Expels the product when the valve is opened.
• It aids in atomization or foam production of the
product.
VARIOUS TYPES OF PROPELLANTS:
A) Liquefied Gases Propellants
B) Compressed Gases Propellants
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I PROPELLATNS

6. A) Liquefied Gases Propellants:
• These are Gases at room temp and atmospheric
pressure.
• They are liquefied by lowering the temp.
• When they are place in the container they are
immediately separated into Liquid and Vapor phase.
• They are of Following types:
CHLOROFLURO
CARBONS
FLORINATED HYDRO
CARBONS
HYDROCARBONS
EX- di-chloro-di-
flouro-methane(12)
EX- Di-flouroethane EX- Butane ,Propane
Used for Oral
Inhalation
preparation.
Used for Oral
Inhalation
preparation.
Used for Topical
preparation.
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7. B) Compressed Gas Propellants:
Some gases can be compressed in small volume and
remain in the gaseous form. When these are used to
provide pressure to remove product from the aerosol they
can called as compressed gas propellants.
• These are having High Purity
• Also, Having High Stability.
• Nitrogen, Nitrous Oxide, Carbon Dioxide are some of
its example.
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8. 7/01/2021 8
PRODUCT

9.  The containers, must withstand pressures as
high as 140 to 180 psig at 1300 F
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II CONTAINERS
V
arious materials
Were used as
containers A. Metal –
• 1.Tinplatedsteel
• A. Side – seam(three
– piece )
• B . Two – piece or
drawn
• C .Tin – free steel
• 2. Aluminum
• a. Two – piece
• b.One – piece (extruded
or drawn)
• 3. Stainless steel
B. Glass
• a. Uncoated glass
• b.Plastic –
coated glass

10. I .Tinplated containers
• They consists of a sheet of steel plate that has
been electroplated on both sides with tin
• The thickness of the tin coating is described in terms
of its weight , e.g.-#25,#50 and #100
• Tinplated steel is obtained in thin sheets, and when
required, it is coated with an organic material
• These are most used containers as they are light
In-expensive and durable.
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A METAL

11. II. Aluminum containers
II. Aluminum Containers (canisters)
• Aluminum is used to manufacture extruded
(seamless) aerosol containers.
• Manufactured by impact extrusion process.
• Used for Inhalation and Topical aerosols.
• Light weight, Less Compatible to corrosion, less
fragile are some of advantages of Aluminum
Containers.
• Disadvantages-
a. Corroded by pure water and pure ethanol.
b. High Cost
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12. III. Stainless Steel Containers
• These containers are limited to the smaller sizes ,
owing to production problems as well as cost.
• They are extremely strong and resistant to most
materials.
• Stainless steal containers have been used for
inhalation aerosols.
• They do not require coating like other containers.
• Expensive, Restricts its size to smaller size are some
of its disadvantages.
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13. • Glass containers are available with or without plastic
coatings.
• Corrosion problems are eliminated and allows a greater
degree of freedom in design of the container.
• Their use is limited due to brittleness property.
• Use in MDI and Topical Aerosols
• Advantages: Less chemical compatibility, Corrosion Free
etc.
• Disadvantages: Accidental breakage, Not suitable for
Photosensitive material.
• Two types are available in them;
1)Uncoated glass containers.
2) Plastic Coated containers.(prevent shattering)
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B. GLASS CONTAINERS

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15. Defined as a device that is used to seal the aerosol
container and to permit controlled discharge of the
contents.
Components of Valve:
 The normal aerosolvalvehas 7 basicparts:
1. Actuator: Controls pattern.
2. Stem: Controls flow
3. Stem Gasket: The “ON/OFF” Switch
4. Housing (Body): Encloses spring/stem &
controls flow.
5. Spring Mounting: Closes Valve
6. Mounting Cup (With mounting & gasket): The
link between the can & valve.
7. Dip Tube: Draws product valve upward.
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III VALVE

16. Formulation of pharmaceutical Aerosols
 Contains two essential components
 Product concentrate
 Propellant
 Product concentrate contains ingredients or mixture of
active ingredients and other such as solvents,
antioxidants and surfactants.
 Propellant may be single or blend of various
propellants
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17.  Solution system (Two Phase System)
 Water based system ( Three Phase System)
 Suspension or Dispersion systems
 Foam systems
 1. Aqueous stable foams
 2. Non aqueous stable foams
 3. Quick-breaking foams
 4. Thermal foams
 Intranasal aerosols
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TYPES OF SYSTEM

18.  Contains both vapor & liquid phase.
 Drug soluble in propellant – no other solvent is
required .
 Propellant 12 orA– 70 – single or mixture
 Example:
Weight %
Active ingredients To 10 -15
Propellant To 100
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TWO PHASE SYSTEM

19.  Large amounts of water can be used to replace all or
part of non – aqueous solvents
 The products are emitted as a spray or foam
 Contains water phase, vapor phase and the propellant.
 Water immiscible with propellant – solubility increased
by adding,
 Co – solvent (ethanol)
 Surfactants (0.5% - 2.0%) – non polar ( esters
of oleic acid, palmitic acid, stearic acid)
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20.  Using suspending agent.
 Oral inhalation aerosols.
 Active ingredients dispersed in propellant or mixture
 Physical stability by,
- Control of moisture content
- Active ingredients with minimum solubility in propellant.
- Propellant density
- Suspending agents
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21.  Consists of aq. or non aq. vehicles, propellant &
surfactants.
 Four types ,
 Aqueous stable foams
 Non aqueous stable foams
 Quick breaking foams
 Thermal foams
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22.  Intended for the deposition of medication into the nasal
passage ways
 Drugs intended to produce local or systemic effect can
be used
 A new alternative is pressurized metered nasal aerosols
 Advantages:
 Excellent depth of penetration
 Reduced droplet or particle size
 Example: Oxytocin Nasal Spray.
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23. Apparatus
I.. Cold filling apparatus
II.. Pressure filling apparatus
III..Compressed gas filling apparatus
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MANUFACTURINGOF PHARMACEUTICALAEROSOL

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25. MethodA
 Product concentratechilledto -30 to -40o F.
 Chilled product added to chilled container.
 Chilled propellantadded through inlet valve.
Method B
 Product concentrateand propellant chilledto -30 to - 40o F.
 Mixture added to chilled container.
 The valves are set in place.
 Filled containerspassed through water bath (contentsheated to
130o F).
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26.  Containers dried, capped and labeled.
Advantage
 Easy process
Disadvantage
 Aqueous products, emulsions cannot be filled.
 For non aqueous systems, moisture appears in final
product.
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27. 7/01/2021 27
PRESSURE FILLING APPRATUS

28.  Consists of metering burette – measures the
amount of propellant to be filled.
Method
 Product concentrate is filled through the burette at
room temperature.
 Propellant is added through the inlet valve.
 Flow of propellant stops when pressure of filling
propellant become equal to the pressure within the
container.
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29.  Propellant – compressed gas
 Pressure reduced by pressure reducing valve
 Pressure used – 150 psig
METHOD
 Product concentrate placed in container
 Valve crimped in its place
 Air evacuated by vacuum pump
 Filling head inserted into valve opening
& gas allowed to flow into container.
 Container shaken during and after filling by
mechanical shakers.
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COMPRESSED GAS FILING APPRATUS

30. It Includes Tests of:
 Propellants
 V
alves, Actuator and Dip Tubes
 Containers
 Weight Checking
 Leak Testing
 Spray Testing
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31.  Vapor pressure is determined and compared to
Specifications
 The density is determined by hydrometer.
PARAMETER TESTED BY
Identification
(of propellant and when
a blend of propellant is
used , to determine its
composition)
Gas Chromatography
Purity and acceptability Moisture, Halogen,
Non-VolatileResidue
Determinations
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32.  Take 25 valves and placed on containers
 Filled with specific test solution
 Actuator with 0.020 inch orifice is attached.
(containers placed at temp. 25±10 C)
 Valve is actuated to fullest extent for 2 sec.
 Repeat for total of 2 individual delivery from each
25 test units.
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33.  Valve delivery per actuation in µL =
Individual delivery wt in mg
Specific gravity of test solution
 Valve Acceptance
 The test procedure applies to two categories of metered
aerosol valves having the following limits
For valves Delivering The limits are
54µL or less ± 15%
55 to 200 µL ± 10%
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34. Of 50 individual deliveries
(1)If four or more are outside limits : the valves are
rejected
(2)If three individual deliveries are outside limits :
another 25 valves are sampled and the test is
repeated
Lot is rejected if more than one delivery is outside the
specification.
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35.  Both uncoated and coated metal Containers are
examined for defects in lining.
 Quality control aspects include specifications for the
degree of conductivity of an electric current as a
measure of exposed metal.
 Glass containers examined for Flaws.
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CONTAINERS
It is done,
»To clear the dip tube of pure propellant and Concentrate.
»To check for defects in the valve and spray pattern.
SPRAY TESTING

36. WEIGHT CHECKING
 Add tared empty aerosol container to filling lines which after filling with
concentrate are removed and then weighed.
 Same procedure is used for checking weight of Propellants.
 The finished container is weighed to check the accuracy of filling.
 For metal containers done by measuring the Crimp dimensions & ensure
that they meet specifications.
 Final testing of the valve closure is done by passing filled
containersthrough water bath.
 Periodic checks are made of the temperatureof the water bath.
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LEAK TEST

37. A. Flammability & Combustibility
1. Flash point
2. Flame Extension / Projection
B. Physicochemical characteristics
1. V
apor pressure
2. Density
3. Moisture content
4.Identification of Propellants
5.Concentrate– propellant ratio
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C. Performance
1. Aerosol valve discharge rate
2. Spray pattern
3. Dosage with metered valves
4. Net contents
5. Foam stability
6. Particle size determination
7. Leakage
D. Biological testing
1.Therapeutic activity
2.Toxicity studies
EVALUATION TEST OF PHARMACEUTICALAEROSOLS

38. Flash Point Flame Projection
 The aerosol product is chilled
to a temperature of about-250F
and transferred to the test
apparatus
 Test liquids temperature is
allowed to increase slowly and
the temperature at which
vapours ignite is taken as Flash
Point.
 Apparatus : Open Cup Tag
 This test indicates effect of
aerosol formulation on the
extension of open flame.
 Product is sprayed for 4 sec
into a flame & exact length is
measured with ruler.
 Below is the Apparatus used for
Flame Projection test.
A. FLAMABILITY AND COMBUSTIBILITY
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39. Property Method
1. Vapor pressure Can Puncturing Device
2. Density Hydrometer
 Pycnometer
3. Moisture  Karl Fischer Method,
 Gas Chromatography
4. Identification Gas Chromatography,
IR Spectroscopy
7/01/2021 39

40. 1 Aerosol valve discharge rate
 Aerosol product of known weight is taken and discharged for a given
period of time.
 By reweighing the container after time limit has expired, the change in weight
per time dispensed is the discharge rate (g/sec).
2 Spray Pattern
 The method is based on the impingement of spray on piece of paper that
has treated with Dye-Talc mixture
 The particle that strike the paper cause the dye to go solutionand to be
absorbed onto the paper
 This gives a record of the spray can be used for comparison purposes.
7/01/2021 40

41. 3. Dosage with Metered Valve
Reproducibilityof dosage determinedby
»Assay Techniques
 Where one or two doses are dispensed into a solvent or onto a
material that absorbs the active ingredients.
 These solutionscan then be assayed , and the amount of
active ingredients determined.
4. Net contents
 Several methodscan be used.
 Tared cans have been placed onto the filling lines are
reweighed and the difference in weight is equal to the net
content.
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42. Methods :
Visual Evaluation
Rotational Viscometer
6.Partical size determination
Methods :
Light Scatter Decay
Cascade Impactor
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a) Light ScatterDecay
 As aerosol settles under turbulent conditions, the changes
in light intensity of a Tyndallbeam is measured

43. 1.TherapeuticActivity 2.Toxicity
• For Inhalation Aerosols : Depends
on the particle size distribution.
• For TopicalAerosols: Is applied to
test areas and adsorption of
therapeutic ingredients can be
determined.
• For Inhalation Aerosols : Exposing
test animals to vapor sprayed from
aerosol container.
• For Topical Aerosols : Irritation &
chilling effects are determined.
• Degree of chilling depends on the
type and amount of propellant
present.
• Thermistor probes attached to
recording thermometers used to
indicate the change in skin
temperature.
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44. 7/01/2021 44
NEWER DEVELOPMENTS
• At present, there is much interest in developing MDIs
for a variety of conditions, including asthma,
emphysema, diabetes, AIDS, cancer, heart disease, and
cystic fibrosis.
• Many of these compounds have been developed using
biotechnology processes, and their delivery to the
respiratory system via an MDI is an extremely
challenging undertaking.
• With the introduction of newer, alternative propellants,
the challenge becomes even greater and presents a
unique opportunity for the delivery of these compounds.

45.  Lachman, L., Lieberman, HA., 2009. The theoryand practiceof
industrial pharmacy, special Indian ed. CBS publishersand
distributorsPVT. LTD, New Delhi , 589-618.
 Sciarra, JJ., Stoller, L., 1998. The science and technology of
aerosol packaging .AWiley – interscience publication, Newyork,
247-255.
 John J Sciarra and Christhopher J Sciarra, Remington Essentials
of Pharmaceutics, Edited by Linda Felton, 633-651.
 Search Engine: Google and You tube.
 Wikipedia.
7/01/2021 45
REFERENCES