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Pharmaceutical Aerosols

Quality Control Department


Dr Amir Ramzy

Pharmaceutical Aerosols
Definitions:
o
o
o

Disperse phase system in which solid particles or liquid droplets constitute the disperse phase and
gas in the continuous phase
System that depends on the power of compressed or liquefied gas to expel the content from
container.
Its a package contains the product and a propellant capable of expelling that product through an
opened valve.

Classification of Aerosols
Space spray:
Dispensation as a fine
spray
Particle size 50

Surface coat:
Produces a wet coat
Particle size are 200 in
diameter

Advantages:
1. Dose is removed without contamination of
remaining materials.
2. Stability is enhanced for those substances
adversely affected by oxygen and or
moisture.
Sterility can be maintained When it is an
important factor,
3. The medication can be delivered directly to
the affected area in a desired form, such as
spray, steam, quick breaking foam or stable
foam.
4. Reduce Irritation produced by the
mechanical application of topical
medication.
5. Ease, convenience of application.
(Application of medication in thin layer).

Foams:
Product comes out in
the form of a
foam/froth

Disadvantages:
1. Expensive.
2. Disposal of empty aerosol containers are
difficult.
3. Due to volatility of the propellant/scan
irritate the injured skin.
4. Some persons may be sensitive to the
propellant/s and persons who using an
inhalation aerosol/s,

The fluorinated hydrocarbons may cause


carcinotoxic effects on rapid and repeated use
of the aerosol product.

5. Aerosol packs must away from temperature


and fire, because it may develop high
pressure inside the container leads to
explosion.
6. If the drug is not soluble in the propellant,
aerosol formulation is difficult.
7. Sometimes propellants may cause toxic
reactions, if therapy is continued for a long
period of time.

Components of aerosol package:


1. Propellants:
o
o
o
o
o

Develop pressure within container to expel product when the valve is opened.
Serves as solvents, suspending agents or dileunts.
These are compressed gases at 70 to 80 p.s.i.g
Compressed gases such as CO2 or nitrogen
Liquefied gases like halogen derivatives such as some saturated hydro carbons like methane
ethane etc ...

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Pharmaceutical Aerosols
Quality Control Department
Dr Amir Ramzy
A large no of liquid propellants some of which are refrigerants gases also have been developed
Eg. T.F.D.C.E ,T.C.M.F.E etc ....
Liquefied gas are preferred comparing to compressed gas
o Compressed gas
1. Pressure are in order of 70-80 psig
2. High tensile material steel and glass
o Liquefied gases:
1. Constant pressure is maintained till last drop
2. Low pressure used 30-40 psig
3. Material other than steel can be used for packing.
Based on material to be prepared to be propelled:
Two phase system
Three phase system
This system is comprised of the
This system is comprised of a layer of
liquid phase, containing the liquefied water-immiscible liquid propellant, a layer
propellant and product concentrate,
of highly aqueous product concentrate,
and the vapor phase.
and the vapor phase.
o
o
o

Product is solid and insoluble in


propellant
Or it is solid or liquid which dissolves
in it.
If a product is insoluble solid than it
can be suitably suspended and
system will have one liquid phase
and a gaseous phase

Product is immiscible with propellant and


dissolved in liquid which also does not mix
with propellant
o Gas
o Product and
o Liquid propellant

2. Containers:

Container material are designed such that they withstand pressures as high as 140 to 180 p.s.i.g at 54C
1. Metals such as aluminium, stain less steel and tin plated steel
Very rare incompatible cases
Stain less steel containers are generally avoided because of high cost
2. Glass uncoated or plastic coated In Glass containers practically no corrosion
3. Plastics polymeric amides, acetyl co polymers

3. Valves
o
o
o

The modern day aerosol valves are Multifunctional i.e they deliver product in desired form
As well as in measured quantities when ever required
Components of aerosol valves:
1.
2.
3.
4.
5.
6.

Gaskets: affix valve on container


Housing
Stem
Dip tube
Valve body or housing
Spring

Metered valve aerosols


o Some metering type of valves have been designed which permit only a specified amount of product
to come out at any go
o Such valves actually consist of two valve's chambers both of which are connected to actuator
When actuator button is in closed position upper chamber valve is in closed position and power chamber
valve is open required amount of product is filled.

4. Actuator
Actuators enable closing and opening of the valves
To ensure that aerosol product is delivered in the proper and desired form.

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Pharmaceutical Aerosols
Quality Control Department
Dr Amir Ramzy
Different types of actuator:
1. Spray actuator
2. Foam actuator
3. Solid steam actuator
4. Special actuator

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Pharmaceutical Aerosols
Quality Control Department
Dr Amir Ramzy

Manufacturing
In general manufacturing of aerosol takes place in two stages
1. Manufacturing of concentrate
2. Addition of propellant
o This manufacturing procedure is quite different from non-aerosol pharmaceuticals product
o This require Q.C measures during filling operation to ensure both concentrate and propellant are
brought together in the proper proportion
o The aerosol concentrate is prepared and sample is tested (early detection prevents loss of other
components)
o Once the propellant is added product is sealed in to a container with a valve methods
1. Cold filling method
2. Pressure filling method
This method requires chilling of all components
This method is carried out at room temperature
including concentrate and propellant to temperature utilizing pressure equipments
-30f or- 40 F
The type of product and size of container usually influence method to be used
Cold filling method
1. Product concentrate is chilled to -40 F
2. Added to the chilled container
3. Then the chilled propellant is added
Alternate methods is to chill both concentrate and propellant in a pressure vessel to -40 F
And then added mixture to aerosol container
A valve is then crimped
Then the container passed through a heated water bath in which content are heated to 130 F
This is to test for leak and strength of container
Container is air dried and spray tested if necessary
Drawbacks
o This method is restricted to non aqueous products
o And those products not adversely affected by low temperatures in the range of -40 F
o
Pressure filling method
o When first developed its slower than cold f filling method
o With development of new techniques speed of this method has been greatly increased.
1. Concentrate added to container at room temperature
2. Valve is crimped
3. Then the propellant is added through the valve/ under the cap
Since the valve contain extremely small opening (0.018 to 0.030 inch), this step is slow and limits
production
o With development of rotary filling machines which allow propellant to be added around and through
the valve stem the speed has been increased
For those products adversely affected by air the air in headspace is evacuated prior to adding of propellant
o

Pressure method is preferred to the cold method


1. As some solutions, emulsions, suspensions and other preparations cant be chilled
2. There is less danger of contamination of the product with moisture
3. High production speed can be achieved
4. Less propellant is lost
5. And the method is not limited

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Pharmaceutical Aerosols
Quality Control Department
Dr Amir Ramzy

Quality control and evaluation of pharmaceutical aerosols:


Quality control tests
includes:
1.
2.
3.
4.
5.
6.

Propellants
Valves, Actuator. Dip Tubes
Containers
Weight Checking
Leak Testing
Spray Testing

Evaluation tests:
A.
B.

C.

D.
E.

Flammability & combustibility:


a. Flash point
b. Flash Projection
Physicochemical characteristics:
a. Vapor pressure
b. Density
c. Moisture content
d. Identification of Propellants
Performance:
a. Aerosol valve discharge rate
b. Spray pattern
c. Dosage with metered valves
d. Net contents
e. Foam stability
f.
Particle size determination
Biological testing:
a. Therapeutic activity
Toxicity studies

1. Propellants
o
o

All Propellants are accompanied by Specification sheet. Parameter Tested By Identification Purity
Gas Chromatography Moisture, Halogen,
Non-Volatile Residue Determination

2. Vales, Actuator, Dip-tubes


o
o

This done according to standard procedure as found in Military Standards MIL-STD-105D". For
metered dose aerosols test methods was developed by Aerosol Specification Committee
industrial Pharmaceutical Technical Section Academy Of Pharmaceutical Sciences
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.

3. Containers:
o

Containers are examined for defects in lining. Q.C aspects include 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.
Leak test:
Leak test is done by measuring the Crimps dimension and ensuring that they meet specification
Final testing of valve closure is done by passing filled containers through water bath (temp is checked
repeatedly and values are recorded)
o

Spray testing:
It is done to clear tube of pure propellant and concentrate to check for defects in valves and spray pattern
Leakage test:
1234-

Weigh 10 can units and calculate the mean value =W1


Immerse the 10 can units in water bath for 15 min adjusted on temperature 50 C
Re-weight the 10 can units after drying =W2
The test is passing if there is no visual leakage observed and the difference between the initial and final weight
is less than 1.0%.

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Pharmaceutical Aerosols
Quality Control Department
Dr Amir Ramzy

A.

Flammability and combustibility

1- Flash point: Apparatus: Open Cup Tag Apparatus


Test liquids temp. is allowed to increase slowly & temp. at which vapors Ignite is called as
Flash Point.
2- Flame Projection: Product is sprayed for 4 sec onto flame & exact length is measured with
ruler.

B. Physiochemical characteristics

The pressure can be measured simply with a pressure gauge /through use of water bath ~test gauge and
special equipments like
1- Vapor Pressure Can Puncturing Device.
2- Density >> Hydrometer, Pycnometer.
3- Moisture Karl Fisher Method~
4- Identification Gas Chromatography, >> IR Spectroscopy.

C. Performance
1) Aerosol valve discharge rate: Aerosol product of known weight is discharged for specific
time. By reweighing the container, the change in the wt. per time dispensed is the Discharge
rate in gm/sec.
2) 2. Spray pattern: The method is based on the impingement of spray on piece of paper that
has treated with Dye-Talc mixture.
3) 3 dosage with metered valves: Reproducibility of dosage determined by: Accurate weighing
of filled container followed by dispensing several dosage. containers again reweighed & diff.
in wt. divided by no of dosage dispensed gives average dose.
4) Net contents:
Tarred cans placed on filling lines are reweighed & then
Difference in wt is equal to net content.
In Destructive method: opening the container & removing as much of product possible.
Mean volume of can concentrate and mean weight of propellant gas:
1) Weigh each can unit individually 1 each initial unit weight= W1
2) Des-cramping the can unit to discharge the gas 1 re-weight the can with its des-cambered valve=
W2
3) The different between W1-W2 =the propellant weight
4) Repeat the last steps for 10 can units and calculate its mean value= mean weight of propellant gas
5) Using measuring cylinder to measure the volume of each can concentrate solution of 10 unit
6) Calculate the mean value = Mean volume of can concentrate
5. Foam stability:
o The life of a foam can range from few seconds to an hour Various Methods are used
o Visual Evaluation,
o Time for given mass to penetrate the foam,
o Time for given rod to fall which is inserted into the foam,
o Rotational Viscometer.

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