PHARMACEUTICAL

AEROSOLS

Presented By :
Mr. Naresh Rajgor,
Assistant Professor,
M.P. Patel College of Pharmacy,
Kapadwanj
PHARMACEUTICAL

AEROSOLs
DEFINITION
“Aerosol is pressurized dosage form in which
therapeutically active drug is dissolved or dispersed or
suspended in compressed or liquefied gas to expel the
content from the container in the form of spray.”
OR
“A system that depends on the power of compressed
or liquefied gas to expel the contents from the
container.”
• Aerosol mainly used for the
treatment of Asthma and COPD
disease etc….
• Aerosols are used for either topical ,
oral or nasal administration in the
form fine particles or mist or fog.
• In mid 1950 the pharmaceutical
aerosol introduced in market.
ss
 Components of aerosols
Aerosol consist of
1. Product concentrate
2. Propellant
3. Container
4. Valve and actuator
1. PRODUCT CONCENTRATE
It consist of API, Additives
like suspending agent,
emulsifying agent ,
antioxidant, aqueous and
non aqueous, co-solvent
etc…
 2. PROPELLANT
• It is responsible for developing the vapour pressure with
in the container and also expel the product when the
valve is opened and in the atomization or foam
production of the product.
It is classified in to mainly three types
1. Liquified gas system
a) Flourinated hydrocarbon(FHC)
b) Chloro fluro carbon (CFC)
C) Hydrocarbons (HC)
2. Compressed gas system
3.Hydrofluoroalkanes
 1. LIQUIFIED GAS SYSTEM
• These compounds are gases at room temperature and atmospheric
pressure .However they can be liquefied easily by lowering the
temperature (below the boiling point or by increasing pressure ).
• These compounds are chosen generally have B.Pt below 700F and
vapour pressure between 14 and 85 psia at 700 F
• When it is placed into sealed container it immediately separates into
a liquid and a vapour phase.
• Some o f the propellant molecule will leave from the liquid state to
vapor state. The pressure at this point is called vapour pressure
• It is denoted by the symbol Psia (pounds per square inch absolute)
• As molecule enter the vapor state a pressure gradually develops
• no .of molecule in vapour state = vapor pressure
• PHYSIOCHEMICAL PROPERTIES OF
PROPELLANTS are
• Vapor pressure
• Boiling points
• Liquid density
• Vapor pressure of mixture of propellants is calculated by
Doltan’s law which states that total Pressure in any
system is equal to the sum of individual or partial
pressure of various compounds.
• Raoult’s low regards lowering of the vapor pressure of
a liquid by the addition of another substance, states that
the dispersion of the vapor pressure of solvent upon the
addition of solute is proportion to the mole fraction of
solute molecules in solution.
• The relationship can be shown mathematically
3. CONTAINER
1. Tin plate containers

• It consist of a sheet of steel plate that has been

electroplated on both sides with tin.
• The size of the container is indicated by a standard
system and measured by height and weight.
2. Aluminum containers
• greater resistance to corrosion
• Light weight, not fragile
• Good for light sensitive drugs
3. Stainless steel container
•Limited for smaller size.
•Extremely strong and resistant to most materials.
•Pressure stand.

4. Glass containers
•Available with plastic or without plastic coating.
•Compatible with many additives.
•No corrosion problems.
•Can have various shape because of molding.
•Fragile.
•Not for light sensitive drugs.
4. Actuator and valve
2. Stem:
• it is made of nylon /delrin/s.steel
• It contains one or more orifice (0.013 to 0.030)
3. Gasket :
• It is made of Neoprene rubber
4. Spring:
• It is used to hold the gasket in a place and when actuator is depressed it
returns the valve in closed position
• It is made of stainless steel
5. Dip tube :
• It is made up of poly propylene material / poly ethylene
• Inside diameter (0.120 – 0.125) for tube and viscous product is 0.195
 B. Metering Valve
• Metering valves are applicable to the
dispensing of potent medication.
• These operate on the principle of a chamber
whose size determines the amount of
medication dispensed.
• Approximately, 50 to 150 mg of liquid material
can be dispensed at one time with use of such
valves.
FORMULATION OF PHARMACEUTICAL AEROSOL
 1. SOLUTION SYSTEM
• This system referred to as a two phase system and
consists of two phases: a vapor phase and a liquid phase.
• When the active ingredients are soluble in the
propellant, no other solvent is required.
• Depending on the type of spray required, the propellants
are used.
• Propellant 12 produce fine particle, but when the other
type of propellant is added with this one, it reduces the
vapour pressure and produce large particles.
• The amount of propellant used may vary from 5% to 95%.
• This system can be best explained by the following general
formulations.

Weight (%)
• Active ingredientsto 10-15
• Propellant 12/11 (50:50)to 100
• Solution aerosols produce a fine to coarse spray, depending on the
concentration of the other ingredients.
• Hydrocarbon propellants A-70 produces a drier particles, while A-17
and A-31 tend to produce a wetty spray.
 2. WATER BASED SYSTEM
• It is three phase system containing vapour phase,
propellant , water.
• Some non- aqueous solvents replace with water
so called as a water based system so called as a
spray or foam system.
• Ethanol used as a co-solvent to solubilize the
propellant in water.
• Surfactants (0.5-2%) have been used to a large
extent to produce a satisfactory homogeneous
dispersion.
• Propellant content varies from 25 -60%.
• A recent development that is useful for
pharmaceutical aerosols is the Aquasol valve.
• This new Aquasol system allows for the
dispensing of a fine mist or spray of active
ingredient and dissolved water, which is not
possible with three phase system.
• Since only water and active ingredient are
dispensed.(propellant is in vapor phase and have
a little quantity.)
• Depending on the configuration of the valve and
actuator, either a fine dry spray or a coarse wet
spray can be obtained.
 3. SUSPENSION SYSTEM
• Various methods have been used to overcome the difficulties
encountered that are due to the use of co-solvent.
• It is prepared by dispersion active ingredients in mixture propellant and
by using suspending agent.
• The system have been developed primarily for the use with oral
inhalation aerosols.
• Ex: Weight (%)
Epinephrine bitartrate 0.50
Sorbitan trioleate 0.50
Propellant 114 49.50
Propellant 12 49.50
• The epinephrine bitartrate has a minimum solubility in
the propellant system, but is sufficiently soluble in the
fluids in the lungs to exert a therapeutic activity.
• The physical stability of an aerosol dispersion can be
increased by
1. control of moisture content.
2. Use of derivatives of active ingredient having minimum
solubility in propellant.
3. Reduction of initial particle size to less than 5 micron.
4. Use of dispersing agents.
• In this system, there are chances of agglomeration.
Various agents like isopropyl myristate and mineral oils
are used to reduce agglomeration.
 4. FOAM SYSTEM
• They contain Dispersion of API, Vehicle, surfactant
and propellant. Liquefied propellant used as
internal phase.
a. Aqueous stable foam :
• Ingredients( antiseptic )
• oil waxes
• O/W surfactant
• Water
• Hydrocarbon propellant
b. Non aqueous stable foam
• Non-aqueous stable foams may be formulated
through the use of glycols (PEG).
• Emulsifying agent used this type PEG Esters
(PEG monostearate).
• Ingredients
• Glycol 91-92.5 %
• Emulsifying agent 4%
• Hydrocarbon propellant 3.5-5.0 %.
 c. Quick breaking foam
• In this system, the propellant is in the external phase.
• When dispensed, the product is emitted as a foam, which then
collapses into a liquid.
• This type of system is especially applicable to topical medication,
which can be applied to limited or to large areas without the use of
mechanical force to dispense the active ingredients.
• Ex:
• Ethyl alcohol 46-66 %
• Surfactant 0.5-5 %
• Water28-42%
• Hydrocarbon propellant 3-15%
 d. Thermal Foams
• These foams were developed several years
ago and were used to produce a warm foam
for shaving.
• They were not readily accepted by costumer.
• The same technology were used for hair color
and dyes, but unfortunately they were subject
to some problem.
 5. INTRANASAL AEROSOLS
• Drug delivery through intra nasal has long
been used as most effective way for
administration of drugs.
• Until recently, the modes of administering
intranasal preparations have been limited to
nasal drops, non pressurized nasal sprays,
inhalants, intra nasal gels, creams and
ointments.
• A new alternative to this preparation is the
pressurized meter nasal aerosols.
• The advantages through the intranasal ways
are measured dose of drug, depth of
penetration into the nasal passageway, reduce
droplet size, lower dose than other route etc.
• Ex:
• Active ingredient 1.0 %
• Dispensing agents, additives 1.0 %
• Propellant (12/11) 98%
 Name of the available products.
Sr. No Trade Name Dosage Form Active Ingredient Indication
1 Decadron Pressurized Dexamethasone Allergic or
Turbinaire aerosol sodium phosphate inflammatory
suspension nasal condition
2. Beconase or Pressurized Beclomethasone Seasonal and
Vancenese aerosol dipropionate perennial
suspension rhinitis.
 TYPES OF AEROSOLS DELIVERY
• Nebulizers
• Used to administer medication to people in the form of a mist
inhaled into the lungs.
• Meter dose Inhaler (MDI)
• It 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.
It is a device used to converting a liquid drug (Solution
/suspension) into a fine mist which can then be inhaled easily

Two types:
• Jet Nebuliser( air jet /air blast)
• Ultrasonic Nebuliser
• It is powered by high pressure air
• Nebulizer commonly used in hospital and home
• for drug administration have small medication
• reservoirs(<10ml)
 METERED DOSE INHALER
• Metered-dose inhalers (MDIs), introduced in the mid
1950.
• In MDIs, drug is either dissolved or suspended in a
liquid propellant mixture together with other
excipients, including surfactants and presented in a
pressurized canister fitted with a metering valve .
• A Predetermined dose is release when up on
actuation.
• When released from the canister the formulation undergoes
volume expansion in the passage within the valve and forms
mixture of gas.
• The high speed of gas flow break the liquid into fine droplets
• MDI are Generally Packed In aluminum steel canister with a
capacity of 20 -30 ml.
• Aluminium is inert material . So either coated with epoxy
material.
• CFC used as a propellant in MDI Preparation along with
surfactant and lubricant.
• eg. CFC -11, CFC -12, CFC-14
• Alternative for propellant CFC – HFA-134,127
 DRY POWDER INHALER(DPI)
• In DPI the drug is inhaled as a cloud of fine
particle .
• The drug is either preloaded in the inhaled
device or filled in hard gelatin capsule .
• DPI are propellant free.
• No additive except carrier like lactose .
• It can deliver large dose than MDI
 MANUFACTURING OF
PHARMACEUTICAL AEROSOL

Apparatus
• COLD FILLING PROCESS
• PRESSURE FILLING PROCESS
• COMPRESSED GAS FILLING PROCESS
 Preparation of product
concentrate
• The aerosol concentrate consists of drug or combination
of drugs, solvents, antioxidants and surfactants
formulated as solution, suspension .
• The aerosol concentrate is first prepared and filled into
the container.
• The propellant is then filled into the container.
Therefore, part of the manufacturing operation takes
place during the filling operation measures to ensure
that both concentrate and propellant are brought
together in the proper proportion.
COLD FILLING APPARATUS
• The cold filling aerosol line consists of:
• 1.Un-scrambler
• 2.Air-cleaner
• 3.Concentrate filler (capable of being chilled)
• 4.Propellant filler
• 5.Valve placer
• 6.Vaccum purger
• 7.Valve crimper
• 8.Heated water-bath
• 9.Labeler
• 10.Coder and packaging table
• The principle of cold filling method requires the chilling of all
components including concentrate and propellant to a
temperature of 30 to -40 º F.
• This temperature is necessary to liquefy the propellant gas .
• The cooling system may be a mixture of dry ice and acetone
or refrigeration system.
• First, the product concentrate is chilled and filled into
already chilled container followed by the chilled liquefied
propellant.
• The heavy vapour of the cold liquid propellant generally
displace the air in the container
• Single head or multiple head rotary unit capable of
vacuum crimping up to 120 can / min are available.
• The rotary unit requires air pressure (90 to 120 lbs / inch)
and vacuum.
• A valve is placed either manually or automatically
depending on the production rate required.
• The valve is crimped in place by using valve crimper.
• Advantages
• Easy process
• Disadvantages
• Chilling of the product, container and propellant is required.
• Aqueous products, emulsions and those products adversely
affected by cold temperature cannot be filled by this method.
 TESTING OF FILLED CONTAINER
• The container passes through a heated water
bath in which the contents of the container
are heated to 130ºF to test for leaks and
strength of the container.
The container is air dried, spray – tested,
capped and labeled.