INTRODUCTION

Aerosol or Pressurized package is defined as

―A system that depends on the power of a compressed gas
or liquefied gas to expel the contents from the container.‖

• In 1942 - First aerosol was developed.

• In1950 - Pharmaceutical aerosol for topical

administration was developed.

• In 1955 - Aerosol for the local activity in the respiratory

tract was developed (Epinephrine).
 ADVANTAGES OF AEROSOLS
• A dose can be removed with out contamination of
materials.
• Stability is enhanced for these substances adversely
affected by oxygen and or moisture.
• When sterility is an important factor, it can be maintained
while a dose is being dispensed.
• The medication can be delivered directly to the affected
area in a desired form.
• Irritation produced by the mechanical application of
topical medication is reduced or eliminated.
• Ease and convenience of application.
• Application of medication in thin layer .
• Rapid response to the medicament .
• Portable
 COMPONENTS OF AEROSOLS
• Propellant

• Container

• Valve and actuator

• 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 Propellants

(b) Compressed gases Propellants
 LIQUEFIED GAS PROPELLANTS
• Liquefied propellants are gases that
exist as liquids under pressure.
• Because the aerosol is under pressure
the propellant exists mainly as a liquid,
but it will also be in the head space as a
gas.
• The product is used up as the valve is
opened, some of the liquid propellant
turns to gas and keeps the head space
full of gas.
• In this way the pressure in the can
remains essentially constant and the
spray performance is maintained
throughout the life of the aerosol.
 CHLORO FLUORO CARBONS
• Propellant of choice for oral and inhalation .
Advantages Disadvantages
• Chemical inertness • High cost
• Lack of toxicity • It depletes the ozone layer
• Non flammability.
• Lack of explosiveness.
Examples: Trichloromonofluoromethane - Propellant 11
Dichlorodifluoromethane - Propellant 12
Dichlorotetrafluoroethane - Propellant 114
Chlorodifluoromethane - Propellant 22
Chlorodifluoroethane - Propellant 142b
Difluoroethane - Propellant 152a
 HYDROCARBONS

• Can be used for water based aerosols and topical use.

Advantages Disadvantages
• Inexpensive • Inflammable
• Excellent solvents • Unknown toxicity
• It does not cause ozone produced
depletion
Ex: Propane - Propellant A-108
Isobutane - Propellant A-31
Butane - Propellant A-17
 HYDROFLUORO ALKANES

•These compounds break down in the atmosphere at faster

rate than CFCs.
• Lower ozone destroying effect.

Advantages Disadvantages
• Low inhalation toxicity • Poor solvent
• High chemical stability • High cost
• High purity
• Not ozone depleting

Examples: 1,1,1,2,3,3 3-Heptafluoro propane (HFA-227)

1,1,1,2-Tetrafluoroethane (HFA-134a)
 COMPRESSED GAS PROPELLANTS
• Compressed gas propellants really
only occupy the head space above the
liquid in the can.
• When the aerosol valve is opened
the gas 'pushes' the liquid out of the
can.
• The amount of gas in the headspace
remains the same but it has more
space, and as a result the pressure
will drop during the life of the can.
• Spray performance is maintained Examples: Carbon
however by careful choice of the dioxide, Nitrous oxide
aerosol valve and actuator. and Nitrogen
 CONTAINERS
They must be able to withstand pressures as high as 140
to 180 psig (pounds per sq. inch gauge) at 130 ° F.

AEROSOL CONTAINERS

A . Metals
1. Tinplated steel
2. Aluminum
3. Stainless steel

B. Glass
1. Uncoated glass
2. Plastic coated glass
 TIN PLATED STEEL CONTAINERS

• It consist of a sheet of steel plate, this sheet is coated with

tin by electrolytic process .
• The coated sheet is cut into three desired fabricated
pieces.
• The top, bottom are attached to body by soldering .
• When required it is coated with organic material usually
oleoresin, phenolic , vinyl or epoxy coating
• Welding eliminates soldering process, Saves considerable
manufacturing time and decreases the product/container
interaction.
• Recent developments in welding include Soudronic
system and Conoweld system
 ALUMINIUM CONTAINERS

• Manufactured by impact extrusion process.

• Light in weight, less fragile, Less incompatibility due to
its seamless nature.
• Greater resistance to corrosion .
• Used for inhalation and topical aerosols .
• Pure water and pure ethanol cause corrosion to Al
containers.
• Added resistance can be obtained by coating inside of
the container with organic coating like phenolic , vinyl or
epoxy and polyamide resins.
 STAINLESS STEEL CONTAINERS

• Used for inhalation aerosols

Advantage :
• Extremely Strong.
• Resistant to many materials.
• No need for internal coating.

Disadvantage :
• Costly
 GLASS CONTAINERS
• These containers are preferred because of its Aesthetic
value and absence of incompatibilities.
• These containers are limited to the products having a lower
pressure (33 psig) and lower percentage of the propellant.
•Used for topical and MDI aerosols.

Two types of glass aerosol containers

i) Uncoated glass container:
• Decreased cost and high clarity and contents can be
viewed at all times.
ii) Plastic coated glass containers:
• These are protected by plastic coating that prevents the
glass from shattering in the event of breakage.
 VALVES
• Easy to open and close .
• Capable of delivering the content in the desired form such
as spray, foam, solid stream etc.
• It can deliver a given amount of medicament .

TYPES OF VALVES :

1. Continuous spray valve

2. Metering valves
VALVE ASSEMBLY
 CONTINUOUS SPRAY VALVE
• Used for topical aerosols .

Valves assembly consists :

• Ferrule or mounting cup

• Valve body or housing
• Stem
• Dip tube
• Gasket
• Spring
FERRULE OR MOUNTING CUP :
• Used to attach valve to container.
• Made from Tin plated steel, Al , Brass .
• Under side of the valve cup is coated with single or
double epoxy or vinyl resins.

VALVE BODY OR HOUSING :

• Made up of Nylon or Derlin and contains a opening at the
point of attachment of dip tube. (0.013 to 0.080 inch)

STEM :
• Made from Nylon or Derlin , brass and stainless steel can
also be used. (orifice - 0.13 to 0.040 inch).
GASKET :
• Made from Buna-N and neoprene rubber.

SPRING :
• Made from Stainless steel .
• Used to hold gasket in place.

DIP TUBE :
• Made from Poly ethylene or poly propylene.
• Inner diameter 0.120 – 0.125 inch.
• However for Capillary dip tube inner diameter is 0.050
inch and for highly viscous products it is 0.195 inch.
 METERING VALVES
• Used for dispensing of potent medication.
• Operates on the principle of a chamber whose size
determines the amount of medication dispensed.
• Approximately 50 to 150 mg ±10 % of liquid materials
can be dispensed at one time with the use of such valve.

MDI

Metering valve
 ACTUATORS

• Ensures that aerosol product is delivered in the proper

and desired form .
• These are specially designed buttons which helps in
delivering the drug in desired form i.e., spray, wet stream,
foam or solid stream .

TYPES OF ACTUATORS :
• Spray actuators
• Foam actuators
• Solid steam actuators
• Special actuators
SPRAY ACTUATORS:
• It can be used for topical preparation, such as antiseptics,
local anesthetics and foot preparation .
• It allows the stream of product concentrate and propellant
to pass through various openings and dispense as spray.
FOAM ACTUATORS :
• It consist of large orifice which ranges from 0.070—
0.0125 inch .
SOLID STREAM ACTUATORS :
• These actuators are required for 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.
SPRAY

ACTUATORS ACTUATORS

FOAM
 METERED DOSE INHALERS
• Used to minimize the number of administration errors.
• To improve the drug delivery of aerosols particles into the
drug delivery system of the nasal passageways and respiratory
tract.
Advantages of MDI:
• It delivers specified amount of dose .
• Small size and convenient .
• Usually inexpensive .
• Quick to use .
• Multi dose capability more than 100 doses available .
Disadvantages of MDI :
• Difficult to deliver high doses .
• Most products have low lung deposition .
• Drug delivery highly dependent on good inhaler technology.
Metered Dose Inhalers (MDIs)
 FORMULATION OF AEROSOLS
• It consist of two essential components :
1. Product concentrate and
2. Propellant

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

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

1. Physical, chemical and pharmacological properties of

drug.
2. Site of application .
 TYPES OF SYSTEMS

TYPES OF AEROSOL SYSTEMS :

• Solution system
• Water based system
• Suspension or Dispersion systems
• Foam systems
1. Aqueous stable foams
2. Non aqueous stable foams
3. Quick-breaking foams
4. Thermal foams
• Intranasal aerosols
 SOLUTION SYSTEM

• Solution aerosols produce a fine to coarse spray.

• Two phase system consisting of Vapor and Liquid phase.
• No solvent is required, if active ingredient is soluble in
propellant.
• The vapor pressure of system is reduced by the addition of
less volatile solvents such as ethanol, propylene glycol,
glycerin, ethyl acetate.
• Amount of Propellant may vary from 5% (for foams) to
95% (for inhalations).

General formula weight %

Active drug -10-15%
Propellant 12/11 (50:50) - 100%
INHALATION AEROSOL :
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
container.

HYDROCARBONS IN TOPICAL AEROSOL PHARMACEUTICAL

PREPARATIONS :
Formulation Weight %
Active ingredient - 10-15
Ethanol - 10-15
Water - 10-15
Hydro Carbon propellant (A-46) - 55-70
• Depending on water content the final product may be
solution or three phase system.

• Hydrocarbon propellant A-70 produces drier particles

while A-17 and A-31 tend to produce a wetter spray.

• These are useful for topical preparations.

• Packaged in Plastic coated glass containers.

 WATER BASED SYSTEM

• 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.
• 0.5 to 2% of surfactant is used.
• Surfactants with low water solubility and high solubility
in non polar solvents will be most useful eg: 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, non flammability of the product .
• Fine and dry spray is obtained using 6 parts of water
with 1 part of Hydrocarbon propellant, even it
extinguishes fire.
• Alcohol use results in the two phase system, however
flammability is increased.
• In Aquasol system vapor phase of Propellant and
product enter actuator through separate ducts or channels.
• Moving at tremendous velocity , the vaporized
propellant enters in to the actuator while the product is
forced into the actuator by the pressure of the propellant.
• At this point product and vapor are mixed with violent
force results in uniform finely dispersed spray.
• Depending on the configuration of the valve and
actuator , either a fine dry spray or coarse wet spray is
obtained .
 SUSPENSION SYSTEM
• It involves dispersion of active ingredient in the propellant
or mixture of propellants.
• 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 Microns) 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:

1. Control of moisture content. (< 300 ppm)

2. Reduction of initial particle size to less than 5 µm for

inhalation.

3. Adjustment of density of propellant and suspensoid so

that they are equalized.

4. Use of dispersing agents.

5. Use of derivatives of derivatives of drug with minimum

solubility in propellant system.
• Physical stability of a dispersed system depends on rate of
agglomeration of the suspensoid.
• Agglomeration results in valve clogging , inaccuracy of
dosage and depending on the nature of active ingredients,
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, sesquioleate).
• Surfactants are effective in a concentration of 0.01 to1 %.
 FOAM SYSTEMS
• 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.
• Liquefied propellant is emulsified and found in the internal
phase.
AQUEOUS STABLE FOAM :
Formulation %w/w
Active ingredient
Oil waxes
o/w surfactant 95-96.5
Water
Hydrocarbon Propellant (3 -5%) 3.5-5
• Total propellant content is usually (3 to 5% W/W or 8-10%
V/V) .
• As the amount of propellant increases a stiffer and dryer
foam is produced.
• Lower propellant concentrations yield wetter foams.
• Hydrocarbon and compressed gas propellants are used.

NON-AQUEOUS STABLE FOAM :

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.
QUICK BREAKING FOAM :

• Propellants are in 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 soluble in alcohol and water.
THERMAL FOAM :
• Used to produce warm foam for shaving
• Used to dispense hair colors and dyes but were
unsuccessful due to corrosion.
INTRANASAL AEROSOLS :
• Intended to deposit medication into nasal passages for
local or systemic effect.
• To deliver measured dose of drug.
• Require lower doses compared to other systemic products.
• Excellent penetration into the nasal passage way.
• Decreased mucosal irritability .
• Maintenance of sterility from dose to dose.
• Difference from inhalation aerosol is in the design of
adaptor.
Manufacture of aerosols
 MANUFACTURE OF PHARMACEUTICAL AEROSOLS

• Pressure filling apparatus

• Cold filling apparatus
• Compressed gas filling apparatus
PRESSURE FILLING APPARATUS
• It consists of a pressure burette capable of metering small
volumes of liquefied gas into the aerosol container under
pressure.
• An inlet valve is located at the bottom or top of the
pressure burette
• 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 or compressed air is
attached to the upper valve, the pressure exerted by
nitrogen helps in the flow of the propellant into the
container.
• Another device capable of maintaining positive pressure
and consisting of piston arrangement can also be used for
pressure filling.
• This type of device cannot be used for filling inhalation
aerosols which have metered valves.
PROCEDURE:
• It is a slow method compared to cold filling method.
• 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 new 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.
• This is done so as to protect the products from getting
adversely affected.

ADVANTAGES OF PRESSURE FILLING:

• 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.

DISADVANTAGE:
• 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.
• Various units used in pressure filling apparatus are
arranged in the following order :
Unscrambler , Air cleaner , Concentrate filler , Valve placer ,
Propellant filler , Valve crimper , Water bath , Labeler ,
Coder and Packing table .
• Purger and vacuum crimper are added .
• Followed by a pressure filler.
• The do not have the facility of refrigeration as chilling is
not required.
• Vacuum crimper and pressure filler comes under single
unit if filling is carried by ‗under the cap‘ method.
Pressure filling apparatus Pressure burette
 COLD FILLING APPARATUS

• 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 at the
floor level.
• Fluorocarbon vapors do not form any explosive or flammable
mixture though their vapors are heavier than air.
PROCEDURE:
• 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 1or 2
stages. Depending on the amount.
• 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 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 filler ,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.
Advantage:
• Easy process .
Disadvantages :
• Aqueous products, emulsions and those products adversely
affected by cold temperature cannot be filled by this
method.
 COMPRESSED GAS FILLING APPARATUS

• 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 head.
• A flow indicator is also present in specialized equipments.

PROCEDURE :
• 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,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 required or for the stability purposes.
• High solubility can be achieved by shaking the container
manually or with the help of mechanical shakers.
 QUALITY CONTROL TESTS

It includes the testing of

1. Propellants
2. Valves, Actuators and Dip Tubes
3. Containers
4. Weight Checking
5. Leak Testing
6. Spray Testing
 1. PROPELLANTS :
• Vapor pressure and density of the propellant are
determined and compared with specification sheet.

Parameter Tested By

Identification Gas Chromatography

Purity and acceptability Moisture, Halogen,

Non-Volatile Residue
determinations
 2. VALVES , ACTUATORS AND DIP TUBES :

• Sampling is done according to standard procedures as found

in Military Standards ―MIL-STD-105D‖.

• For metered dose aerosol valves ,test methods were

developed by
‗Aerosol Specifications Committee‘
‗Industrial Pharmaceutical Technology 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.
 TEST SOLUTIONS
Ingredients Test Test Test
% w/w Solutions ‘A’ Solutions ‘B’ Solutions ‘C’

Iso Propyl Myristate 0.10% 0.10% 0.10%

Dichloro Difluoro 49.95% 25.0% 50.25%

methane
Dichloro tetrafluoro 49.95% 25.0% 24.75%
ethane
Trichloro monofluoro - - 24.9%
methane
Alcohol USP - 49.9% -

Specific Gravity @ 1.384 1.092 1.388

25 c
 Testing Procedure:
• Take 25 valves and placed on containers filled with specific test
solution.
• Actuator with 0.020 inch orifice is attached.
• Temperature -25±1°C.
• Valve is actuated to fullest extent for 2 sec and weighed.
• Again the valve is actuated for 2 sec and weighed.
• Difference between them represents delivery in mg.
• Repeat this for a total of 2 individual deliveries from each of 25
test units.
Individual delivery wt in mg.
Valve delivery per actuation in µL =
Specific gravity of test solution

Valve Acceptance: Deliveries Limit’s

54µL or less 15%
55 to 200 µL 10%
• Of the 50 individual deliveries, if 4 or more are outside the
limits : valves are rejected

• If 3 deliveries are outside limits : another 25 valves are

tested.
Lot is rejected if more than 1 delivery is outside the
specifications.

• If 2 deliveries from 1 valve are beyond limits : another 25

valves are tested.
Lot is rejected if more than1 delivery is outside
specification.
3. CONTAINERS :
• Containers are examined for defects in lining.
• Quality control aspects includes degree of conductivity of
electric current as measure of exposed metals.
• Glass containers examined for Flaws.

4. WEIGHT CHECKING :
• Is done by periodically adding to the filling line tared
empty aerosol containers, which after filling with concentrate
are removed & weighed.
• Same procedure is used for checking weight of Propellants
being added.
5. LEAK TESTING :
• It is a means of checking crimping of the valve and detect
the defective containers due to leakage.
• Is done by measuring the Crimp‘s dimension & comparing.
• Final testing of valve closure is done by passing the filled
containers through water bath.

6. SPRAY TESTING :
• Most pharmaceutical aerosols are 100% spray tested.
• This serves to clear the dip tube of pure propellant and
pure concentrate.
• To check for defects in valves and spray pattern.
 EVALUATION TESTS

A. Flammability and combustibility :

1. Flash point
2. Flash 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:
Apparatus : Open Cup Tag Apparatus
Product is chilled to – 25°F and test liquid
temperature is allowed to increase slowly & temperature at
which vapors Ignite is called as Flash Point .
2. Flame Projection:
Product is sprayed for 4 sec
into a flame & exact length is
measured with ruler.
 B. Physicochemical characteristics:

Property Method

1. Vapor Pressure » Can Puncturing Device.

» Pressure gauge
2. Density » Hydrometer,
» Pycnometer.
3. Moisture » Karl Fisher Method,
» Gas Chromatography.
4. Identification of propellants » 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 after the time limit, the change in
the weight per time dispensed is the Discharge rate ( gm/sec).

2. Spray pattern :
• The method is based on the
impingement of spray on
piece of paper that has been
treated with Dye-Talc
mixture.
 3. Dosage with metered valves :
• Reproducibility of dosage determined by:
»Assay
»Accurate weighing of filled container followed by dispensing
several dosage.
containers again reweighed & difference in weight divided by
number of dosage dispensed gives average dose.
4. Net Contents :
• Tared 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.
 5. Foam stability :
Methods : » Visual Evaluation,
» Time for given mass to penetrate the foam,
» Time for given rod to fall which is inserted
into the foam,
» Rotational Viscometer.

6. Particle Size Determination :

Methods : » Cascade Impactor,
» Light Scattering Decay.
a). Cascade Impactor :
Principle :
Stream of particle projected
through a series of nozzle and
glass slides at high velocity,
larger particle are impacted
on low velocity stage and
smaller particles are collected
on higher velocity stage.
b). Light Scattering Decay :
Principle :
As aerosol settles under turbulent
condition, the changes in the light
intensity of a tyndall beam is measured.
 D. Biological testing:

1.Therapeutic Activity :
» For Inhalation Aerosols : depends on the particle size.
» For Topical Aerosols : is applied to test areas and adsorption
of therapeutic ingredient is determined.
2.Toxicity :
» For Inhalation Aerosols : exposing test animals to vapor
sprayed from aerosol container.
» For Topical Aerosols : Irritation and Chilling effects are
determined.
 CONCLUSION

• At present there is much interest in developing MDIs

for conditions including asthma, diabetes, AIDS, cancer,
heart disease and cystic fibrosis etc.
• Many of compounds have been developed using
biotechnology process and their delivery to the
respiratory system via MDI in an extremely challenging
undertaking.
• As Hydrofluorocarbon (HFC) propellants cause ozone
depletion , they are being replaced with acceptable
Hydrofluoroalkanes (HFA) propellants.
 References:

• “The Theory & Practice Of Industrial Pharmacy” by Leon Lachman

, H.A.Lieberman.

• Remington’s “The Science & Practice Of Pharmacy” 3rd Edition,

Volume-I.