Aerosols

Vijayalakshmi

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 a stable 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 of liquefied gases Responsible for maintaining pressure Acts as solvent or vehicle for the product concentrate Compressed gases like carbondioxide ,nitrogen,nitrous oxide are employed as propellants Chloro-fluorocarbons were used as propellants
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Propellants

Eg:dichloro-difluoro methane, dichloro tetrafluoro ethane, trichloromonofluoro methane Fluorinated hydrocarbons are gases at room temperature 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 replaces the non aqueous solvents Depending on the formulation emitted as spray or foam. Surfactants, cosolvents are used
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Water based system

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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 or valve components

Eg:trichloromonofluoro methane tends to form hydrochloric 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 the propellant
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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, container and 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 the product
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Containers

Glass, uncoated or plastic coated Metal including tin plated steel, aluminum and stainless 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

Chemical compatibility More adaptive

Advantages

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 of dose

Materials used in the manufacture of valves must 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 the valve Product is discharged from the orifice Type and quantity of propellant used control the particle size
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Stem

Supports the actuator Delivers the formulation in the proper form to the chamber of the actuator Placed closely with the stem Prevents leakage of the formulation when the valve is closed

Gasket

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 Is directly below the mounting cap Links the dip tube and the stem and actuator 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 the product and intended delivery

Housing

Dip tube

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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 the atmosphere In this position chamber is filled with the contents of the chamber Depression of the actuator causes simultaneous reversal 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 for the 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
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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Pressure filling

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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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