2. These are pressurized package
consists of the gas that may be compressed or liquefied and
it has capability to bring out the drug and other ingredients
out of the container.
Advantage-
Product can be dispensed in desired form like foam (quick
breaking foam, stable foam), spray etc
Product can be dispensed without contamination
Due to unidirectional flow contamination of remaining
product does not occur.
Substances that get spoiled by oxygen or moisture can be
maintained.
3.
4. Container
Type of container may be used
Al
Steel
Glass
Valve
Components of Valves
Ferrule or mounting cap
Valve body or housing
Stem
Spring
Gasket
Dip tube or dip spacer
Actuator
Product concentrate
Propellent
Choroflouro carbon
Hydrocarbon
Compressed gas
Nitrogen
Nitrous oxide
Carbondioxide
5. Container should be Withstand at pressure 140 to 180
psig at 130of and bursting pressure is not less than 300
psig
Types of container used
Aluminum
Steel
glass
aluminum –
most commonly used as container in aerosol
Seamless in nature
light in weight and cost effective
Steel-
Higher cost limit their use
6. Glass
Only used in topical prepration mostly in cosmatic
preparation becose pressure inside the the container should
not be more than 25psig and amount of propellent not more
than 15%w/w
Adantage-
Appealing in nature
Great freedom in design
Disadvantage-
Chances of leaching and sorption
Only used when pressure is less than 25psig
7. Used to keep the pressure within the container.
Components of Valves
8. Ferrule or mounting cap-
Give the proper attachment of the valve with the
container.
Valve body or housing-
Made up of Nylon or delrin
Produce fine particle
Reduce chilling effect of propellent on skin.
Stem-
Made up of Nylon or delrin
9. Spring-
Made up of stainless steel.
Spring keep the valve in close position
Gasket-
Gasket is used for air tight seal.
Made up of Rubber (Butyl rubber, Buna-N,
Neoprine Rubber etc)
Dip tube or Tube spacer-
Should be wider in diameter for easy dispensing
of contents in aerosol.
Dip tube made up of Polyethylene or poly
propylene
10. Warning on a aerosol container-
Keep away from fire and heat
Keep away from children
Highly inflammable
Note –
Metering valve-
Used when drug is potent
Use to dispense accurate amount of drug
11. It is a specially designed button to activate the valve assembly.
Allows easy opening and closing of the valve.
It dispense the product in desired form. Actuator design and
dimensions determine the physical form of the emitted product
concentrate (spray or foam).
Actuators types:
1.Spray type (Various openings 1-3)
2.Foam. (Large orifices)
Stable foam
Quick breakable foam
3.Solid stream- Dispense semisolid product (Large opining – as cream,
ointment)
4.Special applications-(They are designed to deliver the medication to the
appropriate site of action - throat, nose, eye, or vaginal tract).
12.
13. Based on the drug product formulation as
solution,
emulsion,
suspension or
powder
we can have
Solutions aerosol,
emulsion aerosol or
Suspensions aerosols .
Foams are produced when the product concentrate is
dispersed throughout the propellant and the propellant is in
the internal phase; i.e., the emulsion behaves like o/w
emulsion
14. It use to propelled the product outside.
Definition-Propellants are chemicals with a vapor pressure
greater than atmospheric pressure at a temperature of 40˚C.
Propellants are simply compressed gas or liquid under
pressure that can readily be vaporized into the desired
pressurized gas.
It provides the necessary force to expel the contents; it
causes the product to be dispensed as foam or mist/spray,
depending on the formulation and the type of valve
employed.
It is one of the most important components of the aerosol
package (It is said to be the heart of the aerosol).
It also serves as a solvent for certain active ingredient.
15. Chlorofluorocarbons(CFC)/Freones
Most common
Cheap,
Good solvent
Environmental problems (depletes ozone layer)
so priviously used only in Inhalational products.
Because high pressure is require to target the
drug at lungs.
Eg. 114, 012,011
Note-FDA banned use of CFC
Hydrofluorocarbons (HFC)
Replaced CFC
No Environmental problems (does not depletes
ozone layer).
Very costly.
16. Compressed gas
Eg- Nitrogen (inert gas), Nitrous oxide (Laughing gas), carbon
di oxide
Pressure falls during use
Doesn't have any environmental problems
Hydrocarbon propellants
They are highly inflammable/ combusable
Eg- Propane (Most inflammable gas),Butane, Isobutane etc..
Cheap
Good solvent
Doesn't have any environmental problems (no ozone
depletion).
Most commonly used in topically product.
Do not use in inhalational products due to their inflammable
nature.
Bad taste is an additional disadvantage
17. Note-
Single or mixture of propellants are used
Mixture of propellents –
Daltons law- Used to calculate the total
pressure of system.
P = P1 +P2+P3
Raoulds law-
Used to calculate the partial vapor pressure
of individual propellant in the mixture of
propellant.
Ideal solution follow Raould’s law.
19. The container is then passed through a water bath of about 55°C to check for leaks or distortion in the
container.
When filling is complete, the valve assembly is inserted into the container and crimped into place.
The heavy vapors of the cold liquid propellant will generally displace the air present in the container.
The chilled product concentrate is quantitatively added to the equally cold aerosol container and then the
liquefied gas is added.
In the cold fill process, both the product concentrate and the propellant must be cooled to temperatures
below 0°C (-30°C to -40°C) where they will remain liquefied.
MANUFACTURE OF PHARMACEUTICAL AEROSOLS
COLD FILL PROCESS
20. Suitable for-
Suitable for metering valve. (damage will not be
occur.
The cold fill process takes advantage of the
property that some ingredients will liquefy when
cooled.
Aqueous solutions cannot be filled by this process
since the water will turn to ice in the low
temperature
Not suitable for-
Hydrocarbon propellant due to their combustible
properties.
Biphasic system (emulsion, suspension, ointment
etc) due to strong temp variation breaking of
biphasic system will occur.
21. After the filling operation is complete, the valve is tested for proper function.
The entrapped air in the package might be ignored if it does not interfere with the stability
of the product, or it may be evacuated prior to filling or during filling.
Then the liquefied gas, under pressure, is added through the valve.
The product concentrate is placed in the container, the valve assembly is inserted and
crimped into place
MANUFACTURE OF PHARMACEUTICAL AEROSOLS
PRESSURE FILLING METHOD
22. More common than cold filling
Pressure filling is carried out essentially at
room temperature.
It has the advantage that there is less danger
of moisture contamination of the product and
also less propellant is lost in the process.
Not suitable for-
Metering valve- damage will be occur during
filling.
PRESSURE FILL PROCESS
23. Process similar as PRESSURE FILLING
METHOD.
Compressed gas is used instead of CFC
Suitable for biphasic system eg.
Suspension
Emulsion
Ointment etc..
24. A Flammability and combustibility
1. Flame extension/flame projection test
2.Flash point test-Tag open cup appratuse
B.Physicochemical characteristics
1. Vapor pressure –Pressure gause
2. Density- Psychnometer
3. Moisture content (Karl fisher method, Gas chromatography)
C. Performance
1. Spray pattern- By TLC or Dye treated paper
2. Net contents
3. Uniformity of delivered dose
4. Particle size determination
5. Leakage
D.Stability testing
25. Flame Projection/extention Test
Spray for 4 second on flame- measure the
height by ruler
20cm ------- combustible
45cm ------- flammable
Flash point test :
Perform by Tag open cup apparatus :
Aerosol is chilled to -250F.
Temperature at which the vapor ignites is the
Flash point.
Less flash point – more combusible
26. Karl Fisher Method :
Iodine produced at
anode reacts with the
water present in the
sample. When all has
been consumed, excess
of iodine is detected
electrometrically and
that is the indication of
end point.
For propellants 10ppm
28. Weigh the ten full containers.
Empty each container through the valve.
Open each container with tube cutters employing any
safe technique -- e.g. chill to reduce the internal
pressure.
Wash and thoroughly dry each container, valve and all
associated parts.
Weigh the containers, valves and all associated parts.
Subtract the weight of the ten empty containers, valves
and associated parts.
Express the difference in the units of declared on the
label.
29. Total wt of filled aerosol container (wt of
container + wt of product)----dispense
20 dose------reweight
W
n
W Initial weight-Final wt
n No. of dose dispense
Foam stability
Visual examination
Rotational viscometer
30. Applicable for suspension
Methods of particle size determination
Microscopy
Cascade Impactor
Glass Impinger
Time of flight
Laser Diffraction
Phase doppler analysis
Optical particle counter
Note- For inhalational preparations – particle size
range 0.5micro meter
For totical preparations—partical size range –
upto 50 micrometer
31. Topical type Aerosol eg foam type– 5%
w/w
Inhalational type Aerosol -95% w/w
