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It consist of two essential components :
▪ Product concentrate and
▪ Propellant

➢ Product concentrate : Active ingredient or mixture of active ingredients
and other necessary agents such as solvents, anti oxidants and

➢ Propellant : Single or blend of various propellants is used.
Blend of solvents is used to achieve desired solubility characteristics.


• Various surfactants are mixed to give the proper HLB value
for emulsion system.

• The propellants are selected to give the desired vapor
pressure, solubility and particle size.

• Pharmaceutical aerosol may be dispensed as fine mist, wet
spray, quick breaking foam, stable foam, semi solid etc.

Type of system selected depends on
❑ Physical, chemical and pharmacological properties of drug.
❑ Site of application .



• Solution system
• Water based system
• Suspension or Dispersion systems
• Foam systems
• Aqueous stable foams
• Non aqueous stable foams
• Quick-breaking foams
• Thermal foams
• Intranasal aerosols.


• This system is also referred to as “Two phase system” consists of

vapor and liquid phase.
• If active ingredient is soluble in propellant ,no other solvent is

• The vapor pressure of system is reduced by the addition of less

volatile solvents such as ethanol, acetone , propylene glycol, glycerin,
ethyl acetate. This results in production of larger particles upon

• Amount of Propellant may vary from 5% (for foams) to 95% (for

General formula weight %
Active drug – to 10-15
Propellant 12/11 (50:50) – to 100


• Depending on water content the final product may be solution or
three phase system.

• Solution aerosols produce a fine to coarse spray.


Formulation Weight %
Isoproterenol Hcl – 0.25
Ascorbic acid – 0.1
Ethanol – 35.75
Propellant 12 – 63.9
Packed in 15 -30 ml Stainless Steel, Aluminum or glass

Formulation Weight %
Active ingredient -up to 10-15
Ethanol – up to 10-15
Water – 10-15
Hydro Carbon propellant (A-46) – 55-70


• Hydrocarbon propellant A-70 produces drier particles while
propellants A-17 and A-31 tend to produce a wetter spray.

• These are useful for topical preparations.
• Packaged in Plastic coated glass containers.



• Large amounts of water can be used to replace all or part of the non
aqueous solvents used in aerosols.


• Produce spray or foam.
• To produce spray, formulation must consist of dispersion of active

ingredients and other solvents in emulsion system in which the
propellant is in the external phase.

• Since propellant and water are not miscible, a three phase aerosol
forms (propellant, water and vapor phases).

• Ethanol can be used as cosolvent to solubilize propellant in water.
It also reduces surface tension aiding in the production of smaller
particles .

• 0.5 to 2% of surfactant is used to produce a homogenous


• Surfactants with low water solubility and high solubility in non
polar solvents will be most useful eg: Long chain fatty acid esters of
polyhydric compounds including glycol, glycerol and sorbitan
esters of oleic, stearic, palmitic and lauric acids .

• Propellant concentration varies from about 25 to 60%.

❖ Aquasol system (Aquasol valve) – dispensing fine mist
or spray of active ingredient dissolved in water .

• No chilling effect, since only active ingredient and water are
dispensed, propellant is in vapor state.

• Difference between aquasol system and three phase system is
aquasol dispenses fairly dry spray with very small particles.


• It involves dispersion of active ingredient in the propellant or mixture of

• To decrease the rate of settling of dispersed particles, surfactants or

suspending agents can be added.
• Primarily used for inhalation aerosols.
• Example:

Formulation Weight%
Epinephrine bitartrate (1-5 0.50
Sorbitan trioleate 0.50
Propellant -114 49.50
Propellant -12 49.50

• Epinephrine bitartrate has minimum solubility in propellant system but
soluble in fluids in the lungs


Physical stability of aerosol dispersion can be increased by:

• Control of moisture content. (< 300 ppm)
• Reduction of initial particle size to less than 5 µm.
• Adjustment of density of propellant and suspensoid so that they are

• Use of dispersing agents.
• Use of derivatives of active ingredients with minimum solubility in

propellant system.


• Physical stability of a dispersed system depends on rate of
agglomeration of the suspensoid.

• Agglomeration is accelerated at elevated temperatures and it is also
affected by particle size of drug (1-5µ , never > 50 µ).

• Agglomeration results in valve clogging , inaccuracy of dosage and
depending on the nature of active ingredients, it may cause damage to
the liner and metal container.

• Isopropyl myristate and mineral oil are used to reduce agglomeration.
• Surfactants of HLB value less than 10 are utilized for aerosol

dispersions (sorbitan monooleate, monolaurate, trioleate,

• Surfactants are effective in a concentration of 0.01 to1 %.



• Emulsion and foam aerosols consist of active ingredients, aqueous or
non aqueous vehicle, surfactant, Propellant and are dispensed as a stable
or quick breaking foam depending on the nature of the ingredients and
the formulation.


• Total propellant content is usually (3 or 5% w/w or 8-10% v/v) .
• As the amount of propellant increases a stiffer and dryer foam is

• Lower propellant concentrations yield wetter foams.
• Hydrocarbon and compressed gas propellants are used.


Formulation %w/w
Glycol 91-92.5
Emulsifying agent 4
Hydrocarbon propellant 3.5-5

Glycols such as poly ethylene glycols are used.
Emulsifying agent is propylene glycol monostearate


• Propellant is in the external phase .
• When dispensed the product is emitted as a foam, which

then collapses into a liquid.
• Especially applicable to topical medications .

Formulation %w/w
Ethyl alcohol 46-66
Surfactant 0.5-5
Water 28-42
Hydrocarbon Propellant 3-15

• Surfactant should be soluble in both alcohol and water and can
be of non ionic or cationic or anionic type


• Used to produce warm foam for shaving

• Used to dispense hair colours and dyes but were unsuccessful due to
corrosion problems and are expensive, inconvenient to use and lack
of effectiveness.

• Intended to deposit medication into nasal passages for local or systemic effect.
• Deliver measured dose of drug.
• Require lower doses compared to other systemic products.
• Excellent depth of penetration into the nasal passage way.
• Decreased mucosal irritability .
• Maintenance of sterility from dose to dose.
• Greater flexibility in the product formulation.


Quality control for pharmaceutical aerosols
• Propellants
• Valves, actuator and dip tubes
• Testing procedure
• Valve acceptance
• Containers
• Weight checking
• Leak testing
• Spray testing


Vapor pressure, density, purity & acceptability of the propellant are
determined & compared with specification sheet.

2.Valves, Actuator, Dip-tubes
• This done according to standard procedure as found in Military Standards “MIL-STD-

• For metered dose aerosols test methods was developed by ‘Aerosol Specification

Committee’ ‘Industrial Pharmaceutical Technical Section ‘Academy Of Pharmaceutical

• The object of this test is to determine magnitude of valve delivery & degree of uniformity
between individual valves. Standard test solutions were
proposed to rule out variation in valve delivery.


Testing Procedure::
• Take 25 valves & placed on containers, Filled with specific test solution
• Actuator with 0.020 inch orifice is attached.
• Valve is actuated to fullest extent for 2 sec. Repeat this
for total 2 individual delivery from each 25 test units.
• Valve delivery per actuation in μL soln = Individual delivery wt in mg /

Specific gravity of test


• Containers are examined for defects in lining. Q.C aspects includes degree
of conductivity of electric current as measure of exposed metals. Glass
containers examined for Flaws.(defects)

4. Weight Checking
• Weight Checking is done by periodically adding tarred empty aerosol
container to filling lines which after filling with concentrate are removed &
weighed. Same procedure is used for checking weight of Propellants.


•Means of checking crimping of the valve & detect the defective
containers due to leakage.
•Done by measuring the Crimp’s dimension & comparing.
•Final testing of valve closure is done by passing the filled containers
through water bath.

•Most ph aerosols are 100% spray tested.
•This serves to clear the dip tube of pure propellant and pure concentrate.
•Check for defects in valves and spray pattern.



• Pressure filling apparatus
• Cold filling apparatus
• Compressed gas filling apparatus

• It consists of a pressure burette capable of metering small volumes of liquefied gas into

the aerosol container under pressure.
• Propellant is added through an inlet valve located at the bottom or top of the pressure

• The propellant is allowed to flow with its own vapor pressure in the container through

aerosol valve.
• The trapped air escapes out from the upper valve.


• The propellant stops flowing when the pressure of burette and container
becomes equal.

• If further propellant is to be added, a hose (rubber pipe) leading to a
cylinder of nitrogen is attached to the upper valve, the pressure exerted
by nitrogen helps in the flow of the propellant into the container.

• Another pressure filling device makes use of piston arrangement and is
capable of maintaining positive pressure .

• This type of device cannot be used for filling inhalation aerosols which
have metered valves.


• This method involves filling of the concentrate into the container at the

room temperature.
• Then the valve is placed in the container and crimped.
• Through the opening of the valve the propellant are added or it can be

added under the cap.
• Since the opening of the valve are smaller in size ranging from 0.018-

0.030 inches, it limits the production and the process becomes slow.
• But with the use of rotary filling machines and newer filling heads

where the propellants are filled through valve stem, the production rate
is increased.

• The trapped air in the container and air present in head space is
removed before filling the propellant to protect the products from
getting adversely affected.


Various units used in pressure filling line are arranged in the following order :
Unscrambler , Air cleaner , Concentrate filler , Valve placer , Purger ,Valve
crimper , Propellant filler, Water bath , Labeler , Coder and Packing table .
Purger ,valve crimper and pressure filler are replaced with a single unit if
filling is carried by under the cap method.


• Solutions, emulsions, suspensions can be filled by this method as

chilling does not occur.
• Contamination due to moisture is less.
• High production speed can be achieved.
• Loss of propellant is less.

• Certain types of metering valves can be handled only by the cold filling

process or through use of an under the cap filler and valve crimper.
• Process is slower than Cold filling method.


Pressure burette
Pressure filling Equipment



• It consist of an insulated box fitted with copper tubings and the tubings
are coiled to increase the area exposed to cooling.

• The insulated box should be filled with dry ice or acetone prior to use.
• The apparatus can be operated with or without metered valves.
• Hydrocarbon propellant cannot be filled into aerosol containers using this

apparatus because large amount of propellant escapes out and vaporizes.
• This may lead to formation of an explosive mixture .
• Fluorocarbon vapors do not form any explosive or flammable mixture

though their vapors are heavier than air.




• Non aqueous products and products which can withstand low temperatures of – 40°F

are used in this method.
• The product concentrate is chilled to a temperature of – 40°F and filled into already

chilled container.
• Then the chilled propellant is added completely in 1 or 2 stages, depending on the

• Another method is to chill both the product concentrate and propellant in a separate

pressure vessel to – 40 °F and then filling them into the container.
• The valve is placed and crimped on to the container.
• Then test for leakage and strength of container is carried out by passing container into a

heated water bath, where the contents of the container are heated to 130°F. After this,
the containers are air dried , capped and labeled.


Various units used in cold filling methods are : Unscrambler, Air
cleaner, Concentrate filleer, Propellant filler, Valve placer, Valve
crimper, Water bath, Labeler, Coder and Packing table .

The cold filling method is no longer being used, as it has been
replaced by pressure filling method.
• Easy process .
Disadvantages :
• Aqueous products, emulsions and those products adversely

affected by cold temperature cannot be filled by this method.



• Compressed gases have high pressure hence a pressure
reducing valve is required.

• The apparatus consists of delivery gauge.
• A flexible hose pipe which can withstand 150 pounds per square inch

gauge pressure is attached to the delivery gauge along with the filling

• A flow indicator is also present in specialized equipments.

• The product concentrate is filled into the container.
• Valve is placed and crimped on the container.
• With the help of vacuum pump the air is removed from the container.


• Filling head is put in the opening of the valve and the valve is
depressed and the gas is allowed to flow in to container.

• The gas stops flowing if the delivery pressure and the pressure
within the container become equal.

• Carbon dioxide and nitrous oxide is used if more amount of gas is

• High solubility of the gas in the product can be achieved by
shaking the container manually or with the help of mechanical


A. Flammability and combustibility :

1. Flash point
2. Flame Projection
B. Physicochemical characteristics :

1. Vapor pressure
2. Density
3. Moisture content
4. Identification of Propellants.
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
D. Biological testing :
1. Therapeutic activity
2. Toxicity studies


A. Flammability and combustibility
1] Flash Point
• Determined by using the Standard Tag Open Cup Apparatus.
• The aerosol product is allowed to chilled to a temp of about -25 0F & transferred
to test apparatus.
• The test liquid is allowed to increase slowly in a temperature & the temp at
which the vapor ignites is taken as the flash point.
• Calculated for flammable components, which in case of topical hydrocarbons.


Flame Projection
• Effect of an aerosol formulation on an open flame.
• The product is sprayed for about 4 sec into a flame
• Depending on the nature of the formulation, the flame is extended, the
exact length is measured with a ruler.


B. Physicochemical characteristics:

Property Method

1. Vapor Pressure » Pressure gauge

» Can Puncturing Device.

2. Density » Hydrometer,

» Pycnometer.

3. Moisture » Karl Fisher Method,

» Gas Chromatography.

4. Identification of propellants » Gas Chromatography,

» IR Spectroscopy.


❑Measurement Of Vapor Pressure
• To determine pressure variation from container to container.
• Determine by pressure gauge or can puncturing device.
• Variation in pressure indicates the presence of air in headspace.

❑Measurement Of Density
•Determination by Hydrometer or a Pycnometer.
•A pressure tube is fitted with metal fingers and hoke valve, which allow for the
introduction of liquids under pressure.
•The hydrometer is placed in to the glass pressure tube.
•Sufficient sample is introduced through the valve to cause the hydrometer to rise
half way up the length of the tube.
•The density can be read directly.


Moisture content
Method used — Karl Fischer method

G. C has also been used
Identification of propellants

I.R spectrophotometry


Aerosol Valve Discharge Rate
• This is determine by taking an aerosol product of known weight and
discharge the content for a given period of time using standard apparatus.
• By reweighing the container after the time limit has expired, the change
in weight per time dispensed is the discharge rate, which can then be
expressed as grams per second.

Spray pattern
• Method is based on the impingement of the spray on a piece of paper that has been
treated with a dye-talc mixture.
• Depending on the nature of the aerosol, an oil-soluble or water-soluble dye is used.
• The particles that strike the paper cause the dye to go into solution and to be absorbed
onto the paper.
• These gives the record of the spray, which can then be used for comparison.


Dosage With Metered Valve
1. Reproducibility of dosage each time the valve is
2. Amount of medication actually received by the patient.
• It is done by assay method.
• Either by spraying the content into the solvent or on the
material which absorb the API. Which then assay for the
content uniformity.


Net content
• Weight of empty container =W1 gm
• Weight of the filled container = W2gm
• Difference in the weight = W1-W2gm net content.
• Distractive method: weight the filled container, dispensing the content
and than contents are weigh.

Foam Stability
• Visual evaluation
• Time for a given mass to penetrate the foam
• Time for a given rod that is inserted into the foam to fall
• Rotational viscometer


Particle size determination
Cascade impactor
Light scatter decay method

Cascade impector.
•Operates on the principle that in a stream of particles projected through a
series of nozzles and glass slides at high velocity, larger particles became
impacted first on the lower velocity stages and the smaller particles pass on
and are collected at higher velocity stages.
•Particle size = 2-8 μ.


❑ Light Scatter Decay
• As the aerosol settles under turbulent conditions, the change in the light
intensity of a Tindal beam is measured.

❑ Leakage
• Select 12 pressurized containers at random, and
• record the date and time to the nearest half hour.
• Weigh each container to the nearest mg, and
record the weight, in mg, of each as W1.
• Allow the container to stand in an upright position at room temperature for
not less than 3 days,
• And again weigh each container, recording the weight, in mg, of each as W2


• Recording the date and time to the nearest half-hour.
• Determine the time, T, in hours, during which the containers were under
• Calculate the leakage rate, in mg per year, of each container from the
expression .
• 365 x 24/T x (W1 – W2).


D. Biological testing: :
1.Therapeutic Activity :
❑ For Inhalation Aerosols : is depends on the particle size.
❑ For Topical Aerosols : is applied to test areas & adsorption of

therapeutic ingredient is determined.

2.Toxicity : »
❑ For Inhalation Aerosols : exposing test animals to vapor sprayed

from Aerosol container.
❑ For Topical Aerosols : Irritation & Chilling effects are determined.


A unique aspect of pharmaceutical aerosols as compared to other dosage forms is that

the product is actually packaged as part of the manufacturing process.
Most aerosols have a protective cap that fits snugly over the valve & mounting cap.
This protect the valve against contamination with dust & dirt
The cap which is generally made up of plastic or metal also serves a decorative

function .



• Expose to temp above 49 C (120 F)
may burst an aerosol container.

• When the containers are cold less
than the usual spray may result.

• These products are generally
recommended for storage between
15C – 30C (59F & 86F)


Medicinal aerosols are labeled by the manufacturer with

plastic peel-away labels or easily removed paper labels.


Aerosols have special requirements for
use & storage:

For safety, labels must warn users
not to use or store them near heat or an
open flame.

Aerosols are labeled with regard to
shaking before use & holding at the


1. Formulation and evaluation of Pharmaceutical Aerosols. {5 marks}



• “The Theory & Practice Of Industrial Pharmacy” by Leon Lachman,
• Remington’s “The Science & Practice Of Pharmacy” 21st Edition,