1) Aerosols use compressed gases or liquefied gases to expel product from containers through special valve systems. Common propellants include HFAs which are safer for the ozone layer than CFCs. 2) Aerosol formulations exist as solutions, suspensions, or emulsions depending on whether the product is soluble or dispersed in the propellant. Solution aerosols produce fine sprays while suspension and emulsion aerosols can produce foams. 3) Key aerosol components include propellants, containers which must withstand high pressures, valves for metering and actuating flow, and formulations incorporating active ingredients and propellants. Aerosols offer advantages like targeted delivery but also have fl

1. PHARMACEUTICAL AEROSOLS

2. AEROSOLS
•
Aerosols - A system that depends on the power of a compressed gas or
liquefied gas to expel the contents from the container with special
valve system.
• 1942 - First aerosol – Good Hue & Sullivan

4. AEROSOLS PRINCIPLE
When a liquefied gas propellant or propellant mixture is sealed within an
aerosol container with the product concentrate, equilibrium is quickly
established between the portion of propellant that remains liquefied and
that which vaporizes and occupies the upper portion of the aerosol
container
The vapor phase exerts pressure in all directions—against the walls of the
container, the valve assembly, and the surface of the liquid phase, which is
composed of the liquefied gas and the product concentrate.
It is this pressure that upon actuation of the aerosol valve forces the liquid
phase up the dip tube and out of the orifice of the valve into the
atmosphere.
As the propellant meets the air, it expands and evaporates because of the
drop in pressure, leaving the product concentrate as airborne liquid
droplets or dry particles, depending upon the formulation.

5. As the liquid phase is removed from the container, equilibrium between the
propellant remaining liquefied and that in the vapor state is reestablished.
Thus, even during expulsion of the product from the aerosol package, the
pressure within remains virtually constant, and the product may be
continuously released at an even rate and with the same propulsion.

7. Advantages
•
•
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•
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•
•
•
•
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Easy and convenient application
Can be delivered directly to the affected area
It prevents oxidation of drugs
Rapid response to the medicament
It can avoid first pass effect
Reduced irritation
Dose can be delivered without contamination
Protect unstable drugs
Portable
It can maintain sterility
It can produce local and systemic effects
Disadvantages
•
•
•
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Expensive
Propellants are toxic
Highly inflammable
Propellants can cause chilling effect to skin

8. Types of drug delivery systems
Nebulizers
used to administer medication to people in the form of a mist inhaled into
the lungs.
Meter dose Inhaler (MDI)
are pressurized, hand-held devices that use propellants to deliver doses of
medication to the lungs of a patient Propellant driven Aqueous pump
sprays
Dry powder inhaler (DPI)
delivers medication to the lungs in the form of a dry powder.

9. Classification of aerosols
According to administration route
– Inhalation aerosols
– Non-inhalation aerosols
– Topical aerosols
According to the working way of valve
– Metered dose aerosols
– Non-metered dose aerosols
According to dispersion system
– Solution aerosols
– Emulsion aerosols
– Suspension aerosols
According to the number of phases
– Two phases aerosols
– Three phases aerosols

11. Components of Aerosols
•
•
•
•
Propellants
Containers
Valves and actuators
Product concentrate
Propellants
Responsible for developing proper pressure within the container.
Provide driving force to expel the product from the container.
Types of propellants
(a) Liquefied gases
(b) Compressed gases

15. LIQUIFIED GAS
FLUORINATED HYDROCARBONS
Used in almost all types pharmaceuticals, Inhalation and oral use
Advantages
– Chemical inertness
– Lack of toxicity
– Non flammability & explosiveness
Disadvantages
– High cost
– It depletes the ozone layer
– Damage Global Warming Potential

16. NOMENCLATURE OF FLORINATED AEROSOLS
EXTREME RIGHT DIGIT INDICATES NUMBER OF FLORINE ATOMS IN THE
MOLECULE
THE SECOND DIGIT IN RIGHT INDICATES ONE GREATER THAN NUMBER
OF HYDROGEN ATOMS IN A MOLECULE
THE THIRD DIGIT FROM RIGHT IS ONE LESS THAN THE NUMBER OF
CARBON ATOMS
If this number is zero it is omitted and two digit number is given

17. HYDROCARBONS
– Can be used for water based aerosols, topical use
Advantages
– Inexpensive
– Excellent solvents
– It does not cause ozone depletion
Disadvantages
– Flammable
– Unknown toxicity produced
e.g. propane , butane , isobutane

18. Recently HFA propellants are used instead of CFC propellants.
Hydrofluoroalkanes
Advantages
Low inhalation toxicity
High chemical stability
High purity
Not ozone depleting
Disadvantages
Poor solvents
High cost
Minor green house effect
Examples
1,1,1,2,3,3,3-Heptafluoropropane
1,1,1,2-Tetrafluoroethane

19. COMPRESSED GASES
- Used when the aqueous phase need not be miscible with the propellant
- Do not have chilling effect, for topical preparation
Advantages
– Inexpensive
– Non flammable
– No environmental problems
Disadvantages
– Pressure falls during use
– Produce coarse droplet spray
– Require use of non volatile co solvent
e.g. CO2, N2O, N2

21. Containers
•
Containers must withstand pressure 140-180 psig at 130°F
Types of Containers
• Metal containers
– Tin Plated Steel
– Aluminum
– Stainless Steel
• Glass containers
- Uncoated glass
- Plastic coated glass
· Plastic Containers

22. Metal Containers
Tin plated steel containers
• It consist of a sheet of steel plate, which is coated on both sides with tin by
electrolytic process
• The coated sheet is cut into three sizes and these sizes are desired fabricated
in to body , top , bottom
• The body is shaped in to cylinder
• The top and bottom are attach to the body by soldering
If internal organic coating is required it is given
Disadvantage: This process is slow and expensive
Recent developments in welding include
Soudronic system- The round bodies are welded with copper wire electrode
and they are sent to conventional line where the bottom and top are attached
Conoweld system – The round body is passed through two rotating electrode
rings and they are sent to conventional line where the bottom and top are
attached

23. Aluminum Containers
• Many pharmaceutical aerosols are packed in Aluminum containers
• Light weight, Less incompatibility due to its seamless nature, Greater
resistance to corrosion
• Used for inhalation and topical aerosols
• Solvents (Pure Water and ethanol) corrode Al containers
• The combination of Anhydrous ethanol and propellant 11 corrode Al,
produces H2 gas, acetyl chloride , aluminum chloride and propellant 21
•
•
•
This can be overcome by anodizing Al or addition of 2-3% water
Non polar solvents are used in Al containers
Creams and ointments

24. Advantages with welding method
•Corrosion minimized
•Decrease product and container interaction
•Saves considerable mfg time
•Non aqueous product can be filled
•Alcohol based pharmaceuticals can be filled
Stainless Steel Containers
•We are going to prepare only Small size containers because of its cost
•Strong
•Reduce corrosion problems
•Used for inhalation aerosols
•No need for internal coating

25. Glass Containers
Compatible with most formulations
Allows for greater degree of freedom in
container design resistant to corrosion, low cost.
Available with or without plastic coating
Limited to use – its brittleness and breakage
Plastic Containers
• Made with acetyl resins or poly propylene
• Can withstand high pressure

26. Types of Containers
METAL CONTAINERS
maximum pressure
(psig)
Temperature (F)
Tin Plated Steel
upto 140
130
Aluminum
upto180
130
Stainless Steel
upto181
130
less than 18
70
Plastic coated glass
less than 25
70
PLASTIC CONTAINERS
less than 26
70
GLASS CONTAINERS
Uncoated glass

27. Valves
It is multifunctional
Easy to open and close
Capable of delivering the content in the desired form
(spray, foam and solid
stream)
It can deliver a given amount of medicament
Materials used in construction of valves should by approved by FDA
Types
• Continuous spray valves
• Metered valves

28. Continuous spray valves
In this type of aerosols the product is released as long as the pressure is maintained in
the actuator
The valve consists of many different parts and is assembled using high speed
production techniques
Ferrule or mounting cup
Valve body or housing
Stem
Gasket
Spring
Dip tube

30. Ferrule or mounting cup
Used to attach valve to container
It is made up of Tin plated steel, Al , Brass (glass bottles),
Under side of the valve cup is coated with single or double epoxy or vinyl resins
(To avoid the effects of oxygen trapped in head space)
They are used with glass bottles and small aluminum tubes
It is attached to the bottle by either rolling or clinching method
Valve body or housing
Made up of nylon or derlin and contains an opening at the point of attachment of
dip tube (0.013 to 0.080 inch)
Housing may or may not contain another opening called VAPORTAP (0.013 to 0.080
inch)
allows escape of vaporized propellant with liquid product
Fine particle
avoids clogging,
inverted position
reduce flame extension and chilling
Stem
Nylon or derlin , metals like brass steel can also be used
Gasket
Buna –N and neoprene rubber
They are compatible with most of the materials

31. Spring
Stainless steel
to hold gasket in place,
Dip tube
Poly ethylene or poly propylene ( more rigid) , I. D- 0.120 – 0.125 inch,
Capillary dip tube – 0.050 inch
Dip tube for Highly viscous products – 0.195 inches
METERING VALVE
•It has defined volume of reservoir
•It can deliver desired volume of medicament by depressing actuator.
•Used for all inhalations and some topical aerosols.
• Applicable to potent medication.

32. ACTUATORS
It is a specially designed button which is fitted to the valve and allows for
easy opening and closing of valve
It delivers the product in a desired form.
It discharges the product as spray, foam, solid stream.
Types of actuators
Spray actuators
It allows the stream of product concentrate and propellant to pass through
various openings ( 0.016 inches to 0.040 inches ) and dispense as very fine
spray
The product is dispensed as a stream rather than as a spray by the actuator
when the propellant conc. is low (50%or less) so for these case Mechanical
break up actuators are used , which are capable of breaking the stream
into fine particles
It can be used for topical preparation, such as antiseptics, local anesthetics
and foot preparation

33. FOAM ACTUATORS
It consist of large orifice (0.070—0.0125inch)
SOLID STREAM ACTUATORS
these actuators are required for dispensing of semi solid products such as
ointments
SPECIAL ACTUATORS
These are used for a specific purpose
It delivers the medicament to the appropriate site of action such as throat, nose,
dental and eyes etc.

34. Formulation
Formulation of aerosols consist of two essential components
Product concentrate
Active ingredient or mixture of active ingredient,
solvents,
anti oxidants,
surfactants.
Propellant
single or blend, is used to give 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

35. Types of Systems
SOLUTION SYSTEM
Large no of aerosol products are formulated.
Solution aerosols produce a fine to coarse spray.
It is also called as Two phase system because it consists of Vapor and
Liquid phase.
No solvent is required, if active ingredient is soluble in propellant.
Depending on the type of spray, propellant 12 or A-70 (very fine particles)
or mixture of propellant 12 and other propellants. If low VP propellants
are added to P-12, large particle size
The vapor pressure of system is reduced addition of less volatile solvents such
as ethanol, propylene glycol, glycerin, ethyl acetate.
Propellant from 5% (for foams) to 95% (for inhalations).
General formula
Active drug -10-15%
Propellant 12/11 (50:50) to 100%

36. Types of Systems
SOLUTION SYSTEM
Large no of aerosol products are formulated.
Solution aerosols produce a fine to coarse spray.
It is also called as Two phase system because it consists of Vapor and Liquid
phase.
No solvent is required, if active ingredient is soluble in propellant.
• Depending on the type of spray, propellant 12 or A-70 (very fine
particles) or mixture of propellant 12 and other propellants. If low VP
propellants are added to P-12, large particle size
• The vapor pressure of system is reduced by addition of less volatile
solvents such as ethanol, propylene glycol, glycerin, ethyl acetate.
• The concentration of Propellant used is from 5% (for foams) to 95% (for
inhalations).
General formula
Active drug -10-15%
Propellant 12/11 (50:50) to 100%

37. Depending on water content the final product may be
solution or
Three phase system.
•
Hydrocarbon propellants
•
A-70 (drier particles)
•
e A-17 and A-31 (wetter spray).
•
These are useful for topical and preparations and in Plastic coated glass
containers when the amount of flamable propellant donot exceed 15 % of
total product weight and the volume capacity of the containers do not exceed
5 fluid ounces
•
Also usefully in inhalation aerosols

38. Water based system
Here the non-aqueous solvents are partly or completely replaced with water
so the name water based system
Depending on formulation they emit spray or foam
Also called as three phase system( water , vapour and propellant phases
The formulation is dispersed in an emulsion system where the propellant is in
external phase
Ethanol: Cosolvent and in production of small particles
Surfactants: low water soluble and high non polar soluble (0.5-2%)
Examples: long chain fatty acid esters of polyhyroxylic compounds
Concentration of propellant: 25-60%
To achieve the desired fine particle size with product containing large
amounts of water and low portion of propellant , a mechanical break up
actuator is used along with the vapour tap valve

39. •
•
•
•
Recent development is use of aquasol valves
Fine mist
No chilling effect
Designed to dispense the product efficiently and effectively using small
amounts of propellants
In aquasol valve the vapour phase of propellant and product enter the mixing
chamber of the actuator separately through seperate ducts
The vapour phase of propellant enters into actuator with high velocity and
the product is also forced into actuator with the pressure of propellant
At this point the product and vapour are mixed thoroughly and results in
uniform , finely suspended spray

40. Suspension or Dispersed system
Here the active ingredient is dispersed in propellant or mixture of propellant
This system is primarily used with oral inhalation aerosols
• Physical stability increased by
Control of moisture content (300 ppm)
– Moisture content of both suspensoid and propellant should be controlled because
high moisture content results in particle agglomeration
– DRYING
Use of derivatives of derivatives of drug with minimum solubility in
propellant
– When the drug is having partial solubility it shows signs of particle growth
Reduction of initial particle size to less than 5 µm for
inhalation.
GRINDING EQUIPMENT

41. Adjustment of density of propellant and suspensoid to equal
by adjusting the density , the rate of settling of the suspensoid can be decreased
The density can be adjusted by addition of a compound of higher or lower density
so that density of suspensoid and propellant are made equal
Use of dispersing agents
Isopropyl myristate and mineral oil are used to reduce agglomeration.
Surfactants of HLB less than 10 are useful (sorbitan monooleate,
monolaurate, trioleate, sesquioleate. (Conc. 0.01 to 1 %)
oleic acid
Dispersing agent
Prevention of particle growth
Valve lubricant

42. FOAM SYSTEMS
Emulsion and foam aerosols consist of
active ingredient,
Aq. or non aq. vehicle,
surfactant,
Propellant.
These systems dispense the product as stable or quick-breaking foams
Liquefied propellant is emulsified and generally in internal phase.
Stable foams
AQUEOUS STABLE FOAM
NON AQUEOUS STABLE FOAM

43. AQUEOUS STABLE FOAM
Active drug
Oil
o/w surfactant
Water( 95-96.5)
HC Propellant (3 -5%)
•Hydrocarbon propellant (3 to 5% W/W or 8-10% V/V usually).
•As the amount of propellant increases a stiffer and dryer
produced.
•Lower propellant concentrations yield wetter foams.
HC and compressed gas propellants are used.
NON- AQUEOUS STABLE FOAM
Water is replaced with glycols such as polyethylene glycols
foam is

44. QUICK BREAKING FOAM
• Propellants are external phase
• Especially applicable to topical medications
•It dispenses the product as foam , which collapses into liquid
Ethyl alcohol ( 46-66%)
Surfactant ( 0.5-5%)
Water ( 28-42%)
HC Propellant (3-15%)
Surfactant should soluble in alcohol and water.
THERMAL FOAM
• To produce warm foam for shaving
• Used for hair colors and dyes
. They are not readily accepted by consumer

45. Manufacturing of Pharmaceutical Aerosols
PRESSURE FILLING
•
Process carried out at room temp
•
HC and FHC prop can be filled by this process
•
Less propellant loss
•
Less moisture contamination of the product
•
Most preferable because some solution , emulsion , suspension , and
other preparation which cannot be chilled.
•
Not used for metered dose inhaler
•
It is not used for inhalation aerosols

46. Method in pressure filling:
The product concentrate is quantitatively placed in the aerosol
Containers
The valve assembly is inserted and crimped into place
The liquified gas under pressure is metered into the valve stem from
pressure burrete
The desired amount of propellant is allowed to enter the container
under its own vapor pressure
When the pressure in the container equals to that in the burette ,
propellant stops flowing.
Additional amount of propellant can be added by increasing the
pressure in the filling apparatus through the use of compressed air of
nitrogen gas

49. COLD FILLING
•
In this method the product concentrate and propellants are
refrigerated to a temperature at least 5°F below their boiling points.(30-40C)
•
The cooling system may be mixture of dry ice or acetone or
refrigiration system
•
The chilled product concentrate is quantitaively metered into cold
aerosol container
•
Then liquified gas is added
•
When sufficient propellant is added , the valve assembly is inserted
and crimped into place
•
Used for inhalation aerosols
•
Used with metered valves and non metered valves
•
Should not use to fill HC propellants

52. Quality Control of Aerosols
Propellants:
All the propellants are shipped to the user along with a specification
sheets. Before propellant is used it is subjected to some tests
A sample of it is sent to laboratory , where its density , vapour
pressure are determined and compared with the specification sheet
And also tests for identification of propellants and if a mixture of
propellants are used their composition is determined by gas
chromatography
The for purity point of view , the moisture content , halogens , non
volatile residual contents are determined and are compared with the
specification sheet
These tests are preformed to ensure that the propellants have not
been contaminated during shipment

53. Valves , actuators and dip tubes
These parts are subjected to both physical and chemical inspection
Metered dose valves:
Valve Delivery rate:
Test procedure:
25 valves are selected , and placed on the containers , into which the
test solutions are filled. A button type actuator with 0.02 inch or larger
orifice is attached
The containers are placed a temperature of 25± 10 C
The valve is actuated to fullest extent for atlest 2 seconds following
complete dispensing of single delivery. This procedure is repeated for
10 times
The test unit is weighed and the valve is actuated to fullest extent for
atlest 2 seconds following complete dispensing of single delivery.
Again it is weighed and the difference between this weight and
previous weight is determined it gives the delivery of the valve

54. The test procedure is repeated for a total of two individual deliveries from
25 containers
The individual delivery weights are divided by specific gravity of test
solution to obtain the valve delivery per actuation
Valve acceptance
The test procedure is applicable to two categories of metered aerosol
valves having
the following limits
For valves delivering
54µl or less , the limits are ± 15%
55 t0 200µl , the limits are ± 10%
1.Of the 50 individual deliveries , if four or more are out side the limits for
the specified valve delivery , the valves are delivery
2.If three individual deliveries are outside the limits another 25 valves are
Samples and test is repeated. The lot is rejected if more than one is out side
the specifications
3. If two deliveries from one valve are beyond the limits , another 25 valves
Should be taken. The lot is accepted if not more than one delivery is out
side the limits

55. Containers:
Weight checking
Leak testing

56. Testing of Pharmaceutical Aerosols
FLAMMABILITY AND COMBUSTIBILITY
•
Flame projection: Extension of an open flame by spraying aerosol
for about 4 sec into the flame.
•
Flash point: Tag open cup apparatus
Product is chilled (-25°F). Allowed to increase the temperature
and temperature at which vapors ignite is taken as flash point.
PHYSICOCHEMICAL CHARACTERISTICS
•
Vapor pressure: pressure gauge , water bath , test gauges
•
Density: Modified Hydrometer or Pycnometer
•
Moisture content: Karl Fischer, GC
•
Identification of propellants: GC, IR
•
Concentration of propellant ratio: GC, IR
•
Specific gravity:
•
High pressure cylinder of 500m capacity

61. PERFORMANCE
Aerosol valve discharge rate:
Take an aerosol , determine its weight and discharge the contents for
specified period of time , reweigh the container ,
Discharge rate :
Change in weight per time dispensed.
Spray pattern
Take a paper , treat the paper with dye-talc mixture
The dye may be oil soluble or water soluble
Impinge the spray on the paper attached to rotating disk , the
particles
that strike the paper causes the dye to go into the solution and gets
absorbed on the paper

62. Dosage with metered valves
- Reproducibility of dosage, each time valve is depressed
Determined by assay techniques where one or two doses are dispensed in a
solvent or any material that absorbs active ingredient
Or
Weigh a container , dispense several doses and once again determine the
Weight . The difference in weight / no doses gives the average dose. This is
repeated and is compared
- Amount of medication actually received by patient.
Net contents:
Wtotal - Wcontainer
Foam stability
- Visual inspection with time.
- Time for a given mass to penetrate the foam.
- Time for the rod inserted in the foam to fall
- Rotational viscometers

63. PARTICLE SIZE DETERMINATION
- Cascade Impactor: 0.1 to 30 microns
- Light scatter decay: Tyndall beam
BIOLOGICAL CHARACTERISTICS
- Therapeutic activity
- Toxicity:
Topical effects – irritating, chilling effect
Inhalation effects (even intended for topical preparations)

64. Thank U