Pharmaceutical Aerosols

Introduction
1. Aerosol is pressurized dosage form in which
therapeutically active drug is dissolved or dispersed
or suspended under compressed or liquified gas to
expel the content from the container in the form of
spray.
2. Aerosol mainly used for the treatment of Asthma.
3. Aerosols are used for either topical, oral or nasal
administration in the form fine particles or mist or
fog.
4. Aerosols are depends on the power of compressed
or liquefied gas to expel the contents from
containers.
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 Advantages
1. A dose can be removed with out contamination of materials.
2. The medication can be delivered directly to the affected area in a
desired form, such as spray, steam, quick breaking foam or stable
foam.
3. Irritation produced by the mechanical application of topical
medication is reduced or eliminated.
4. Ease of convenience of application.
5. Application of medication in thin layer

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1. Produced rapid action
2. It can avoid the hepatic metabolism of drugs.
3. It Prevents to Oxidation of drugs
4. It can be maintain sterility& easy to portable

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• Oropharyngeal region (10-30 micrometer) size
range particles deposited

• Conducting Zone (2-16 micrometer)- Trachea,

Bronchioles,

• Respiratory Zone (<2 micrometer)- Alveolar sac,

alveoli

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Disadvantages
1. Limited safety hazard (Flammable Nature)

2. It is a Costly Preparation

3. It is a chance for continuous deposition of particle

in upper respiratory tract

4. The propellant may cause chillness to the skin.

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 Classification of aerosols

According to administration route

– 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

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PROPELLANTS
A propellant is a chemical with a vapor pressure greater than
atmospheric pressure at 40°C (105°F).

Function:
1) It is responsible for developing the vapor pressure
within the container
2) Expel the product when the valve is opened and in the
atomization or foam production of the product.
3) When the propellant is a liquefied gas or a mixture of
liquefied gases, it can also serve as the solvent or vehicle
for the product concentrate.

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Propellant
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
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While liquefied gas and compressed gas are
similar, their delivery and storage methods are
different.

LNG (liquified natural gas) is frozen in order to

turn it into liquid form, whereas CNG
(compressed natural gas) is pressurized to the
point where it is very compact

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 LIQUIFIED GAS SYSTEM

These compounds are gases at room temperature and

atmospheric pressure.

1. However they can be liquified easily by lowering the

temperature (below the boiling point or by
increasing pressure )

2. These compounds are chosen generally have Boiling point

below 70F and vapour pressure between 14 and 85 psia

3. When it is placed into container it immediately separates

into a liquid and a vapour phase.

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4. Some of the propellant molecule will leave from the liquid state
to vapor state. The pressure at this point is called vapor pressure.

5. It is denoted by the symbol Psia. Psia means = pounds

per square inch absolute.

6. As molecule enter the vapor state a pressure gradually develops

number of molecules in vapor state = vapor pressure

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Propellant

FLUORINATED HYDROCARBONS

It is Used for oral and inhalation aerosol preparation

Chemical Name Numerical Designation

Trichloromonoflouromethane Propellant 11
Dichlorodifluromethane Propellant 12
Dichlorotetrafluromethane Propellant 114
Chloropentaflouroethane Propellant 115

The term psig ( pounds per square inch gauge)

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CHLORO FLURO CARBON (CFC)
Advantages
1. Low inhalation toxicity
2. High chemical stability
3. High purity FHC & CFC Uses
4. CFC-11 is a good solvent
Disadvantages include refrigerants, a
1. Destructive to atmospheric Ozone
erosol propellants in
2. Contribute to “greenhouse effect”
3. High cost medicinal
eg.1. Hydrochlorocarbon applications,
2. Hydroflurocarbon due to their low
3. Hydrochloroflurocarbon toxicity, reactivity and
flammability
Heptafluoro propane (HFA-227)
Tetrafluoroethane (HFA-134a)
Difluoroethane - Propellant 152a
Chlorodifluoromethane - Propellant 22
Chlorodifluoroethane - Propellant 142 b

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HYDROCARBONS

Chemical Name Numerical Designation

Butane Propellant A-17
Isobutane Propellant A-31
Propane Propellant A-108

It is mainly used for the preparation of topical preparation,

1. Chemically stable
2. No hydrolysis
3. Inflammable
4. Low toxicity
5. They are lighter than water

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Compressed Gas Propellants

❖ Gases such as nitrogen, nitrous oxide, and carbon dioxide have been used
as aerosol propellants for products dispensed as fine mists, foams, or
semisolids.—including food products, dental creams, hair preparations, and
ointments. Due to their low expansion ratio, the sprays are fairly wet, and the
foams are not as stable as those produced by liquefied-gas propellants.

❖ Compressed gas propellants only occupy the head space above the liquid in
the container.

❖ When the aerosol valve is opened the gas 'pushes' the liquid out of the
container. 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
container.
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 COMPRESSED GAS SYSTEM
Eg.. Co2 , No,N2

Advantages
1. Low inhalation toxicity
2. High chemical stability
3. High purity
4. Inexpensive–No environmental problem

Disadvantages
1. Require use of a nonvolatile co-solvent
2. Produce coarse droplet sprays
3. Pressure falls during use

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Hydrofluoroalkanes (HFA)-

propellants HFA227 and HFA134a

Hydrofluoralkane showed to be a safe propellent, with pulmonary

deposition ranging from 50 to 60%, and to have significant efficacy,
aerosol propellants in metered-dose inhalers.

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 AEROSOLS CONTAINERS

They must be stand at pressure as high as 140 to 180 psig (pounds per
sq. inch gauge) at 1300 °F.
A. Metals
1. Tinplated steel
(a) Side-seam (three pieces)
(b) Two-piece or drawn
(c) Tin free steel
2. Aluminum
(a) Two-piece
(b) One-piece (extruded or drawn)
3. Stainless steel
B. Glass
1. Uncoated glass
2. Plastic coated glass
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 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

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COMPONENT OF AEROSOLS
VALVE ASSEMBLY

1. Actuator
2. Ferrule or mount cap
3. Valve body or housing
4. Stem
5. Gasket
6. Spring
7. Dip tube

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VALVE ASSEMBLY

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 CONTINUOUS SPRAY VALVE
• Used for topical aerosols .

Valves assembly consists :

• Ferrule or mounting cup

• Valve body or housing
• Stem
• Dip tube
• Gasket
• Spring

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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 - 0.013 to 0.030 inch).
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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.

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 FORMULATION OF AEROSOLS
•It consist of two essential components :
1. Product concentrate and
2. Propellant

Product concentrate :

Active ingredient or mixture of active ingredients 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.
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•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 .

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 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 is pressurized, hand-held devices that use propellants to deliver
doses of medication to the lungs of a patient
i) Propellant driven aqueous pump sprays
ii) Dry powder inhaler -Delivers medication to the lungs in the form
of a dry powder.
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 METERED DOSE INHALER (MDI)

1. Metered-dose inhalers (MDIs), introduced in the mid-1950.

2. 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.

3. A Predetermined dose is release when up on actuation.

4. The high speed of gas flow break the liquid into fine droplets

5. MDI are Generally Packed In aluminum steel canister with

a capacity of 20 -30 ml.

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❑ The metering valve is place in inverted position.

❑ Depression of the valve stem allows the content of the metering

chamber refill with liquid from the bulk is ready to dispense next
dose.

ADVANTAGES OF MDI

❑ Portable

❑ Low cost

❑ Disposability

❑ Hermetically sealed container to prevent oxidation of formulation.

❑ It cause valve clogging due to large particle size.

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 MANUFACTURING OF
PHARMACEUTICAL AEROSOLS

Apparatus

1. Cold filling process

2. Pressure filling process

3. Compressed gas filling process

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 FILLING OPERATIONS
Filling of liquified gas propellent

Two methods are used to manufacture aerosols: the cold fill

process and the pressure fill process.

The cold fill process takes advantage of the property that

some ingredients will liquefy when cooled,

and the pressure fill process uses the property that some
ingredients will liquefy when placed under pressure.

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COLD FILLING 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 1 or 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.

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• The valve is placed and crimped on to 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.

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•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.
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PRESSURE FILLING

•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.

•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.

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•Various units used in pressure filling line are arranged in
the following order :

Unscrambler , Air cleaner , Concentrate filler , Valve placer ,

Purger ,Valve crimper , Propellant filler ,Water bath ,
Labeler , Coder and Packing table .

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ADVANTAGES OF PRESSURE FILLING:

•Solutions, emulsions, suspensions can be filled

by this method as chilling does not occur.

•Contamination due to moisture is less.

•Loss of propellant is less.

DISADVANTAGES :

•Process is slower than Cold filling method.

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 COMPRESSED GAS FILLING

•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.

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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 and the valve is
depressed and the gas is allowed to flow in to container.

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•The gas stops flowing if the delivery pressure and the
pressure within the container become equal.

•High solubility of the gas in the product can be achieved

by shaking the container manually or with the help of
mechanical shakers.

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THANK YOU

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