This document discusses the manufacturing and quality control of pharmaceutical aerosols. It begins by defining aerosols and their classification. It then describes the key components of an aerosol system, including propellants, containers, valves, and actuators. The two main manufacturing methods - cold filling and pressure filling - are outlined. Finally, the document details various quality control tests performed on the propellants, components, containers, and finished aerosol products to ensure quality. These include tests for leaks, spray pattern, weight, delivery rate and more.

1. Manufacturing of
Aerosols and Quality
control
By; Syed Umar Farooq
M.Pharmacy
Department of pharmaceutics
Care college of Pharmacy
Kakatiya university

2. contents
1. Definition
2. Classification
3. Advantages
4. Components of
aerosol system
5. Manufacturing
6. Quality control

3. Definition

4. Product
Produces a
comes out in
wet coat
the form of a
Particle size Particles are
200 in Foam/Froth
50 diameter

5. Advantages
• A dose can be removed with out contamination
of materials.
• Stability is enhanced for those substances
adversely affected by oxygen and or moisture.
• sterility can be maintained When it is an
important factor,

6. Advantages contd….
• The medication can be delivered directly to the
affected area in a desired form, such as
spray, steam, quick breaking foam or stable foam.
• Irritation produced by the mechanical
application of topical medication is reduced or
eliminated.
• Ease of convenience of application. Application of
medication in thin layer

7. Components of aerosol package

8. propellants
• These are compressed gases at 70 to 80 p.s.i.g
• Compressed gases such as CO2 or nitrogen or
• Liquefied gases like halogen derivatives such as some
saturated hydro carbons like methane ethane etc…
• 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….

9. Liquefied gases are preferred
comparing to compressed gases

10. Based on material to be
propelled
Two phase system Three phase system
• Product is solid and • Product is immiscible
insoluble in propellant with propellant and
• Or it is solid or liquid dissolved in liquid
which dissolves in it which also does not mix
• If a product is insoluble with propellant
solid than it can be • Gas
suitably suspended and • Product and
system will have one
• Liquid propellant
liquid phase and a
gaseous phase

12. containers
• Container material are designed such that they with
stand pressures as high as 140 to 180 p.s.i.g at 54 C
1. Metals such as aluminum, 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

14. valves
• 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
• Gaskets :affix valve on container
• Housing
• Stem
• Dip tube

16. Metered valve aerosols
• some metering type of valves have been designed which
permit only a specified amount of product to come out
at any go
• Such valves actually consist
of two valve's chambers both
of which are
connected to actuator

17. 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

18. Actuator
Actuators
enable
closing and
opening of
the valves

19. Manufacturing
In general Manufacturing of
aerosols takes place in two stages
Manufacturing • Addition of
of concentrate propellant

20. • This manufacturing procedure is quite different
from non aerosol pharmaceuticals product
• This require Q.C measures during filling operation
to ensure both concentrate and propellant are
brought together in the proper proportion
• The aerosol concentrate is prepared and sample is
tested (early detection prevents loss of other
components)
• Once the propellant is added product is sealed in to a
container with a valve

21. Methods
• 1.cold filling method 2.pressure filling method
• This method requires This method
chilling of all is carried out at room
components including temperature utilizing
concentrate and pressure equipments
propellant to
temperature -30 f or -
40 f
The type of product and size of
container usually influence method to be
used

22. cold filling method
product
concentrate is
chilled to -40 F
added to the
chilled container
Than the chilled
propellant is added

23. • 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..
• This method is restricted to non aqueous products
• And those products not adversely affected by low
temperatures in the range of -40 F

24. Pressure filling method
• When first developed its slower than cold filling method
• With development of new techniques speed of this
method has been greatly increased
•
Valve is crimped
concentrate added to
container at room
temperature
Then the propellant is
added through the
value /under the cap

25. • Since the valve contain extremely small opening
(0.018 to 0.030 inch)
• This step is slow and limits production
• 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

26. Pressure burette for laboratory
filling of aerosols

27. 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

28. Filling machine

33. Quality Control &
Evaluation Of
Pharmaceutical Aerosols
• QUALITY CONTROL TESTS It Includes
• 1. Propellants
• 2. Valves, Actuator. Dip Tubes
• 3. Containers
• 4. Weight Checking
• 5. Leak Testing
• 6. Spray Testing

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

35. 2.Valves, Actuator, Dip-tubes
• 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.

36. Test Solutions:
• Test Solutions Ingredients % w/w Test
Solutions ‘A’ Test Solutions ‘B’ Test Solutions
‘C’ .
• Isopropyl myristate 0.10% 0.10% 0.10%
• Dichlorodifluoro methane 49.95% 25.0%
50.25%
• Dichlorotetrafluoro ethane 49.95% 25.0%
24.75%
• Trichloromonofluoro methane - 24.9%
• Alcohol USP - 49.9% - Specific Gravity @ 25 °c
1.384 1.092 1.388

37. 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.
• Individual delivery wt in mg. Valve delivery per
actuation in µL = Specific gravity of test sol n Valve
Acceptance : Deliveries Limit’s 54 µL or less ± 15%
55 to 200 µL ± 10%

38. Valve acceptance
• Of 50 delivery If 4 or more are outside
limits : valves are rejected If 3 delivery
are outside limits : another 25 valves are
tested : lot is rejected if more than 1
delivery outside specification If 2 delivery
from 1 valve are beyond limits : another
25 valves are tested : lot is rejected if
more than 1 delivery outside
specification
•

39. 3.Containers:
• 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)

40. 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.

41. 5.Leak Test:
• Leak Test Is done by measuring the Crimp’s
dimension & 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)
6. Spray Testing
. It is done `
To clear dip tube of pure propellant &
concentrate,
To check for defects in valves & spray pattern.

42. Evaluation Tests
• A. Flammability & combustibility:
• 1.Flash point 2.Flash Projection
• B. Physicochemical characteristics:
• 1.Vapour 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

43. A. Flammability &
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.
•

44. B. Physicochemical characteristics:
• The pressure can be measured simply with a
pressure gauge /through use of water bath ,test
gauge and special equipments like
• . Vapor Pressure » Can Puncturing Device.
• 2. Density » Hydrometer, » Pycnometer.
• 3. Moisture » Karl Fisher Method,
• 4. Identification » Gas Chromatography, » IR
Spectroscopy.

45. 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. Spray pattern : The method is based on the
impingement of spray on piece of paper that has
treated with Dye-Talc mixture.

46. 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.

47. 5. Foam stability :
• The life of a foam can range from few seconds
to an hour Various Methods are used
• Visual Evaluation,
• Time for given mass to penetrate the foam,
• Time for given rod to fall which is inserted into
the foam,
• Rotational Viscometer.

48. 6.Partical Size Determination :
• a). Cascade Impactor :
• Principle : Stream of particle projected through a
series of nozzle & glass slides at high velocity, larger
particle are impacted on low velocity stage , &
smaller on higher velocity stage.
• b) . Light Scattering Decay :
• Principle : As aerosol settles under turbulent
condition, the changes in the light of a Tyndall beam
is measured.

49. 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.

50. References:
• The Theory & Practice Of Industrial Pharmacy” by Leon
Lachman, H.A.Liberman, Joseph Kanig, 3 rd
Edition, Varghese Pub., page no. 613-618.
• Remington’s “The Science & Practice Of Pharmacy” 3 rd
Edition, Volume-I, page no.1014-1015.
•