aerosols _ icri , bangalore , india
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Aerosols
Vijayalakshmi
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Definition
Pressurized dosage forms that upon
actuation emit a fine dispersion of liquid or
solid material containing one or more active
ingredients in a gaseous medium
Aerosols expel their contents as fine mist,
coarse, wet or dry spray, a steady steam or astable or a fast breaking foam
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Advantages
Uncontaminated delivery of a portion of drug
Hermetic containers--- protected from oxygen
Opaque containers ----- protected from
atmospheric light
Sterility due to aseptic packing
Topical application feasible
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Advantages
Particle size of the emitted product and its
physical form may be controlled
Dosage can be controlled through the use of
metered valves
Aerosol application is a clean process
requiring little or no wash up by the user
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Principle
Formulation consists of two component parts
Product concentrate
Propellant
Product concentrate is active ingredient
Combined with antioxidants , surface active
agents and solvents
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Principle
Propellant is a liquefied gas or a mixture ofliquefied gases
Responsible for maintaining pressure
Acts as solvent or vehicle for the productconcentrate
Compressed gases like carbondioxide,nitrogen,nitrous oxide are employed aspropellants
Chloro-fluorocarbons were used aspropellants
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Propellants
Eg:dichloro-difluoro methane, dichloro
tetrafluoro ethane, trichloromonofluoro
methane
Fluorinated hydrocarbons are gases at roomtemperature but can be liquefied by cooling
or by compression at room temp.
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Aerosol systems
Pressure and performance
Pressure can be controlled by
Type and amount of propellant
Nature and amount of product concentrate
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Types
Solution system
Two phase system vapor phase and liquid
phase
Active ingredients are soluble in the propellant
Water based system
Water replaces the non aqueous solvents
Depending on the formulation emitted as spray orfoam.
Surfactants, cosolvents are used
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Types
Suspension or disperse systems
Foam systems
Non aqueous stable foams
Quick breaking foams
Thermal foams
Intranasal foams
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Selection of a propellant
Blends of various LG propellants
Non reactive with formulation ingredients orvalve components
Eg:trichloromonofluoro methane tends to formhydrochloric acid with water or ethyl alcohol
No physiological effects
Non irritant
No effect on the absorption of drugs
No cardiotoxic effects
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Two phase systems
Contains liquid phase containing propellant
and product concentrate
Vapor phase
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Three phase systems
Three phases consisting of
Immiscible liquid propellant
Highly aqueous product concentrate
Vapor phase
Dip tube extends only up to product
concentrate (aqueous phase)
Vapor phase is replenished from thepropellant
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Compressed Gas systems
Pressure of the compressed gas in the head
space of the container forces the product
concentrate up the diptube and out of the
valve Nitrogen is the inert gas that can be used
Other gases that can be used are
carbondioxide, nitrous oxide Pressure decreases as the product is used
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Aerosol container and valve assembly
Proper combination of formulation, containerand valve assembly.
Formulation must not chemically interact with
the container or valve components Container and valve must be capable of
withstanding the pressure
Resist corrosion
Valve must contribute to the form of theproduct
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Containers
Glass, uncoated or plastic coated
Metal including tin plated steel, aluminum andstainless steel
Plastics Selection :
Adaptability to production methods
Compatibility with formulation components Sustainability to pressure
Design and aesthetic appeal
cost
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Glass containers
Disadvantage:
Brittleness and danger for breakage
Properly designed to sustain pressure
Advantages
Chemical compatibility
More adaptive
Plastic coated glass containers are used
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Tin plated steel containers
Most widely used metal containers
Starting material is in sheets
Completed aerosol cylinders are seamed and
soldered to provide a sealed unit
Corrosion and leak test perfomed
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Aluminum containers
Manufactured by methods that make them
seamless
Greater safety against leakage,
incompatibility and corrosion
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Stainless steel
Certain small volume containers
Corrosion resistant
Main limitation is higher cost
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Plastic containers
Vapor permeates within the container
Drug plastic interactions
Affect the release of the drug
Reduce the efficacy of product
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Valve assembly
Function :To permit expulsion of the contents of the can
In the desired form ,
At the desired rate and
In the metered dose in the proper amount ofdose
Materials used in the manufacture of valvesmust be
Inert to the formulations Approved by FDA
Plastic ,rubber, aluminum and stainless steel
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Valve assembly
Actuator
Stem
Gasket
Spring
Mounting cap
Housing
Dip tube
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Actuator
The button the user presses to activate the
valve assembly for the emission of the
product
Permits easy opening and closing of thevalve
Product is discharged from the orifice
Type and quantity of propellant used controlthe particle size
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Stem
Supports the actuator
Delivers the formulation in the proper form to the
chamber of the actuator
Gasket
Placed closely with the stem Prevents leakage of the formulation when the
valve is closed
Spring Holds gasket in place
Helps in returning valve to the closed position
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Mounting cap
Attached to the aerosol can or container
Holds the gasket in place Inner part is in contact with the formulation
Housing
Is directly below the mounting cap
Links the dip tube and the stem and actuator Dip tube
Extends from housing down into the product
Brings the formulation from the container to the valve
Diameter of the tube depends on the viscosity of theproduct and intended delivery
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Materials used
Actuator ,stem ,housing and dip tube ---
plastic
Mounting cup and spring --- metal
Gasket --- rubber or plastic resistant to
formulation.
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Metered dose inhalers
Used when the formulation is a potent
medication
Amount of material discharged is regulated
by an auxiliary valve chamber
Single depression of the actuator causes
evacuation of this chamber and delivery of its
contents Controlled by dual valve mechanism
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Metered dose inhalers
Actuator valve closed , chamber is sealed from theatmosphere
In this position chamber is filled with the contents ofthe chamber
Depression of the actuator causes simultaneousreversal of positions
Chamber becomes open to the atmosphere
Release its contents
Becomes sealed from the contents of the container
Upon release of the actuator system is restored forthe next dose
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Filling operations
Cold filling
Both propellant and product concentrate are
cooled to -30 to -40 degrees F
Water systems cannot be filled
Pressure filling
Product concentrate is quantitatively placed in
aerosol container
Liquified gas under pressure is metered into the
valve stem from a pressure burette
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Testing the filled containers
Leak test
Valve functioning
Valve discharge rate
Spray pattern for particle size distribution of
the spray
Accuracy and reproducibility of dosage in
metered valves
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