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PHARMACEUTICAL AEROSOL
Vikrant SalujaFaculty of Pharmaceutical Sciences
PCTE Group of Institutes, LudhianaPunjab, India
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PHARMACEUTICAL AEROSOL
Aerosols are pressurized dosage forms containing one or more
active drug dissolved, suspended, or emulsified in a propellant or
a mixture of solvent and propellant, which is released on actuation
of the valve as a fine dispersion of liquid or solid in a gaseous
medium.
Used for either topical, oral or nasal administration in the form
fine particles or mist or fog.
Mainly used for the treatment of Asthma and COPD disease
Designed to expel their contents as a fine mist, a coarse wet or
dry spray, a steady stream or a stable or fast breaking foam.
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ADVANTAGES
A dose can be removed without contaminationof remaining material.
Prevents Oxidation of drugs
Maintain sterility
Direct application to the affected area.
Irritation produced by the mechanicalapplication of topical medication is reduced oreliminated.
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TYPES OF AEROSOL SPRAY
There are three types of aerosol spray.
1. Space sprays
These products are delivered as a fine mist.
It contains not more than 50 m of particle.
eg. Room sprays
2. Surface coating spray
Aerosols intended for carrying active ingredients to surface are
termed as surface sprays or surface coating spray.
eg. Topical Aerosol
3. Foam spray
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COMPONENT OF AEROSOL
Aerosol consist of
1. Product concentrate
2. Propellant
Productconcentrateconsist of API, additives like suspending
agent , emulsifying agent,antioxidant, aqeous and non aqueous
sovents, cosolvent etc
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PROPELLANT
It is responsible for developing the vapour pressure
with in the container and also expel the product when
the valve is opened and aids in the atomization or foam
production of the product.
It is classified in to mainly two types
1. Liquified gas system
a) Flourinated hydrocarbon(FHC)
b) Hydrocarbons (HC)
2.Compressed gas system eg CO2 , NO, N2
FHC find widespread use in aerosols for oral and inhalation use. HC and compressed gas find widespread use in aerosols for topical
use.
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Liquified gas system
These compounds are gases at room temperature and atmospheric pressure
.However they can be liquified easily by lowering the temperature (below theboiling point or by increasing pressure )
These compounds are chosen generally have B.Pt below 70o F and vapour
pressure between 14 and 85 psia at 70o F.
When it is placed into sealed container it immediately separartesinto a liquid and a vapour phase
Chemical Name Numerical Designation Vapour Pressure (psia)at
70oF
Trichloromonofluoromethane 11 13.4Dichlorodifluoromethane 12 84.9
Dichlorotetrafluoroethane 114 27.6
Butane A-17 31.6
Isobutane A-31 45.8
Propane A- 108 122.8
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CHLORO FLURO
CARBON( CFC)
Advantages
Low inhalation toxicity
High chemical stability
High purity
Disadvantages
Destructive to
atmospheric Ozone
High cost
HYDROCARBONS
Chemically stable
Inflammable
Low toxicity They are lighter than
water
COMPRESSED GAS
SYSTEM
High chemical stability
High purity
Inexpensive
No environmental
problems
Produce course droplet
sprays
Pressure falls during use
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Aerosol PrincipleLiquifiedgas propellant
+
Product concentrate
Equilibriumestablished
(b/w portion of liqified propllent and which
vaporizes and occupies the upper portion
of aerosol container)
The vapour phase exerts pressure and
this pressure upon actuation of the
areosol valve forces the liquid phase
up the diptube and out of the orifice of
the valve into the atmosphere
Propllent meets the air , it expands and
evaporates because of drop in
preassure , leaving the product
concentrate as airborne liquid droplets
ordry partticles
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AEROSOL CONTAINERContainers must withstand pressure as high as 140 to 180 psig
A. Metals
1. Tinplated steel(a) Side-seam (three pieces)
(b) Two-piece or drawn
(c) Tin free steel
2. Aluminium
(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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AEROSOL CONTAINERTypes of containers:
1. Tin platecontainers
Sheet of steel plate that has been electroplated on both sides with tin.
Welded side seam are done using 2 processes: Soudoronicand Conoweld
2. Aluminumcontainers
Greater resistance to corrosion
Light weight, not fragile
Good for light sensitive drugs
3. Stainless steelcontainer
Limited for smaller size
Extremely strong and resistant to most materials
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
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COMPONENT OF AEROSOLS
Actuator Ferrule or mounting cup
Valve body or housing
Stem
Gasket
Spring
Dip tube
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TYPES OF ACTUATOR
Actuators:
These are specially designed button placed onthe valve system which helps in easy opening andclosing of the valve.
It helps in deliver the product in the desired form.
There are different type of actuators are used ,
Spray Actuators Foam Actuators Solid Stream Actuators Special Actuators
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FERRULE/ mounting cup It is used to attach the valve in proper position to the container.
Made from tin-plate steel although aluminium also can be used.
To increase resistance to corrosion a single or double epoxy orvinyl coating can be added.
Valve body / housing T
he part of the valve which holds the stem, gasket and spring inplace and to which the dip tube is attached.
It is made ofnylon/delrin and contains an opening at the point
of attachment of the diptube which ranges from 0.013 to 0.080
inch.
The housing may or may not contain another opening vapourtap
Produce fine particle size
Prevents valve clogging with products containing insoluble
materials
Reduce the chilling effect of propllent on skin
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Stem: It is made of nylon /delrin/s.steel. It contains one or more orifice (0.013 to 0.030)
Gasket : It is made of Buna N, Neoprene rubber
Spring:
It is used to hold the gasket in a place and when actuator isdepressed and released, it returns the valve to its closed position
It is made of stainless steel
Dip tube: It is made up of poly propylene material / poly ethylene
Inside diameter (0.120 0.125 inch) for capillary tubes -0.050
inch and Viscous product - 0.195
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TYPES OF AEROSOL SYSTEM
Solution system / Two phase system
Water based system / Three phase system
Suspension or Dispersion system
Foam system
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Solution system / Two phase system Consists of two phases:
Liquid phase Liquified propellent + Product concentrateVapor phase
Active ingredients soluble in the propllent no other solventrequired.
Generally used propellent may consist of:Propellent 12 Fine sprayMixture of propellent 12 and other propellent Coarse spray
As the amount of propellent 12 is increased, the pressureincreases. The preassure of these system necessitatespakaging the contents in a metal container.
Active ingredients to 10 -15 %
Propellent 12/11(50:50) to 100%
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Waterbased system/ Three phase system
Consist of large amount of water, usually to replace all ora portion of nonaqueous solvents.
Three phase system consists of:A layer of water- immisible liquid propellent
A layer of highly aqueous product concentrateA vapour phase
The formulatio must consist of a dispersion of activeingredients and other solvents in an emulsion system inwhich the propellent is in the external phase.
Ethanol is used as cosolvent in these systems.
Surfactants (0.5-2%) are added for homogenousdispersion.
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Suspensionor Dispersion system
It is prepared by dispersion active ingredients in the
propellent or a mixture of propellants by using suspendingagent.
Developed primarily for oral inhalation aerosols.
Eg. Ephedrine bitartarate aerosol
The physical stability of suspension can be increased by:
Control of moisture content- must be below 300ppm
Use of derivatives of AI having minimum solubility in propellent. Reduction of initial particle size to less than 5microns Adustment of density difference Use of surfactants (HLB < 10; 0.01 1 %)
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Foam system
Consist of AIs, aqueous or non aqueous vehicle, surfactant
and propellant. Dispensed as a stable or quick-breaking foam.
Stable foam
Liquified propellent is emulsified and is found in internalphase Both hydrocarbons and compressed gas propellents may
be used.
Quick breaking foam
Liquified propellent is in the external phase
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MANUFACTURING OF PHARMACEUTICAL AEROSOL
Apparatus
Cold filling apparatus
Pressure filling apparatus
Compressed gas filling apparatus
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PRESSURE FILLING
Pressure filling is carried out at R.T. under high pressure.
The apparatus consists of a pressure burette capable of metering smallvolumes of liquefied gas under pressure into an aerosol container.
The propellant is added through the inlet valve located at thebottom or top of the burette.
The desired amount of propellant is allowed to flow through theaerosol valve into the container under its own vapor pressure.
When the pressure is equalized between the burette and the
container (thus happens with low pressure propellant), thepropellant stops flowing.
To help in adding additional propellant, a hose leading to acylinder of nitrogen or compressed is attached to the upper valveand the added nitrogen pressure causes the propellant to flow.
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Pressure filling apparatus
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ADVANTAGES
It is the preferred method for solutions, emulsions and
suspension.
Less chances for contamination of product
with the moisture.
Less propellant is lost
No refrigeration is required, can be carried out at RT
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COLD FILLING PROCESS
The principle of cold filling method requires the chilling
of all components including concentrate and propellantto a temperature of -30 to -40 F.
This temprature is necessary to liquify the propellant
gas.
The cooling system may be a mixture of dry ice and
acetone or refergiration system.
First, the product concentrate is chilled and filled into
already chilled container followed by the chilled liquefied
propellant.
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Cold filling apparatus
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Advantages
Easy process
Disadvantages
Aqueous products, emulsions and those products
adversely affected by cold temperature cannot be filledby this method.
For nonaqueous systems, some moisture usually
appear in the final product due to condensation of
atmospheric presure
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COMPRESSED FILLING
Compressed gases are present under high pressure in
cylinders. These cylinders are fitted with a pressure reducing
valve and a delivery gauge. T he concentrate is placed in the container
The valve is crimped in place
Air is evacuated by means of vacuum pump
The filling head is inserted into the valve opening, valve
depressed and gas is allowed to flow into the container
For those products requiring an increased amount of gas or
those in which the solubility of gas in the product is necessary,carbon dioxide and nitrous oxide can be used.
To obtain maximum solubility of the gas in the product, the
container is shaken manually during and after the filling
operation by mechanical shakers.
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Evaluationofpharmaceuticalaerosols
A.Flammabilityandcombustibility
Flame extension
Flash point
B. Physiochemicalcharacteristics
Vapour pressure
Density
Moisture content Identification of propellant(s)
C. Performance
Aerosol valve discharge rate
Spray pattern
Dosage with metered valves Net contents
Foam stability
Particle size determination
D.BiologiccharacteristicsE. Therapeuticactivity
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FLAME PROJECTION TEST
This test indicates the effect of
an aerosol formulation on theextension of an open flame.
Product is sprayed for 4 sec.
into flame.
Depending on the nature of
formulation, the flame is extended,
and exact length was measured
with ruler.
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FLASH POINT
Determined by using standard Tag Open Cap Apparatus.
PROCEDURE:
Aerosol product is chilled to temperature of - 25 0 F and
transferred to the test apparatus.
Temperature of test liquid increased slowly, and the
temperature at which the vapors ignite is taken a flash point.
Calculated for flammable component, which in case of
topical hydrocarbons.
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MEASUREMENT VAPOR PRESSURE
To determine pressure variation from container to
container.
Determined by pressure gauge or Can puncturing
device.
Variation in pressure indicates the presence of air in
headspace.
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MEASUREMENT OF DENSITY
Determined by Hydrometerora Pycnometer
Procedure:
A pressure tube is fitted with metal fingers and
hoke valve, which allow for the introduction of
liquids under pressure.
The hydrometer is placed in to the glass
pressure tube.
Sufficient sample is introduced through the
valve to cause the hydrometer to rise half way upthe length of the tube.
The density can be read directly.
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MOISTURE CONTENT
KarlFischermethod Gas Chromatography
IDENTIFICATION OF PROPELLANTS
Gas Chromatography
I.R spectrophotometry
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AEROSOL VALVE DISCHARGE RATE
Expressed as gram per seconds.
Determined by taking an aerosol known weight and discharging
the contents for given time using standard apparatus.
By reweighing the container after time limit has expired, the
change in weight per time dispensed is discharge rate.
Spray pattern
Spray the product on the coated (dye +talc ) paper.
Depending upon the nature of aerosol water /oil soluble dye is
used.
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Dosage with metered valves
Reproducibilityofdosageeach timethevalveis depressed.
Amountofmedicationactually receivedbythe patient.
NET CONTENT
Weight of empty container = gm
Weight of the filled container = gm
net content
FOAM STABILITY:
Visual evaluation
Time for a given mass to penetrate the foam
Rotational viscometer
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Particle size
cascade impactor
Operates on the principle that in a stream of particles
projected through a series of nozzles and glass slides at high
velocity, larger particles became impacted first on the lower
stages and the smaller particles pass on and are collected at
higher stages
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