AEROSOLS
“Pharmaceutical aerosols are pressurized dosage forms that upon actuation emit a fine dispersion of liquid and/or solid materials containing one or more active ingredients in a gaseous medium.”
THE AEROSOL PRINCIPLE:
An aerosol formulation consist of two components
· Product concentrate
· Propellant
1. Upon sealing the container equilibrium is established between liquefied propellant and the propellant, which vaporizes.
2. These vapors exert a pressure on the liquid mixture (product concentrate & propellant), push them out in atmosphere upon actuation.
3. As the propellant comes in the air, evaporates and the product concentrate travels to the target site in the form of air-born liquid droplets or dry powders.
COMPONENTS OF AEROSOL SYSTEM
Ø Container
Ø Valve Assembly
Ø Propellant
Ø Product Concentrate
CONTAINER:
General Features:
For the accurate aerosol system
· The material should be non reactive with formulation components.
· Should be able to with stand high-pressure e.g. 140 pounds/sq. inch gauge.
MACTURING MATERIAL:
Container may be of,
1. Metal
2. Glass
3. Plastic
1. Metals:
· Tin-plated container
· Aluminium
· Stainless steel
i) Tin-Plated Steel Containers:
These are usually three-piece container
a) Cylindrical body having a longitudinal joint
b) Top
c) Bottom
ii) Aluminium
a) One piece container consists of single Aluminium foil having only a hole for valve assembly.
b) Two piece body consist of a cylindrical body having top with no joint and a bottom jointed to cylinder.
iii) Stainless-steel:
These are available in small size only owing to resistant to most materials.
2. Glass:
These are of two types,
· Plastic coated
· Uncoated
Plastic coated container has an advantage over the coated containers as they protect the container from explosion on breaking.
3. Plastic:
Pure plastic container cannot be used because
· Sorption of substances into container walls.
· Leeching of substances from container wall.
· Low-pressure withstand properties.
VALVE ASSEMBLY:
The function of valve assembly to permit expulsion of the contents of the can in the desired form, at the desired rate, and in the case of metered valves, in the proper amount or dose.
Valve assembly consist of
· Actuator
· Stem
· Gasket
· Spring
· Mounting cap
· Housing
· Dip tube
Actuator:
Actuator is the button, which is pushed by the user to activate the valve assembly.
Mounting cap:
Which attaches the valve to the container.
Gasket:
Prevents the leakage of formulation.
Spring:
Hold the gasket the place and bounces back the actuator after the release of pressure.
Housing:
Located below the mounting cap links the dip tube, stem and actuator.
Stem:
Which support the actuator.
Dip Tube:
Extends from housing down into the product, it brings product up to the valve.
PROPELLANTS:
An additive, which expels the contents of the container.
Types:
Propellants are of two types,
· Compressed gases.
· Liquefied gases.
i) Compressed Gases
These are of two types
a) Insoluble gases
e.g. Nitrogen, Argon.
b) Soluble gases
e.g. co2, Nitrous Oxide.
ii) Liquefied gases:
a) Fluorinated Hydrocarbons
e.g.
· Trichloro, monochloro methane
· Dichloro, dilouro methane
· Dilouro methane
· Dichloro tetraflouro ethane
b) Hydrocarbons
e.g.
· Propane
· Butane
· Pentane
· Hexane
PRODUCT CONCENTRATE:
Product concentrate consist of:
· Active ingredients
· Solvent system
· Preservatives / Antioxidants
· Surfactants
AEROSOL SYSTEMS
There are four types of aerosol system.
1. Two phase system
2. Three phase system
3. Compressed gas system
4. Prevalve system
1. Two Phase System:
a) Liquefied phase
b) Gas phase
Example:
i) Solution System:
· Active ingredients are soluble in the propellant.
· Constitutes of Active ingredients+Propellant+Less volatile component e.g. alcohol, ethyl acetate.
· Propellant concentration 5 – 50%
· By lowering the vapor pressure droplet size can be increased
2. Three phase System:
a) Water immiscible liquid propellant
b) Aqueous product concentrate
c) Vapor phase
Examples:
i) Water Based System:
· Active ingredient insoluble in propellant.
· It is an emulsion formulation
· Surfactants are used (conc. 0.5-2%)
· Water act as base
· Propellant conc. 25 – 60%
ii) Dispersion System:
· A.I. is insoluble in water and propellant
· A.I. is dispersed in the form of suspension
· Particle size should be less than 5μm
iii) Foam System:
· Propellant conc. 6-8%
· Consist of emulsion of propellant+water+drug+emulsifier
· Rapid evaporation of propellants from formulation
3. Compressed Gas System:
· Propellant is in the form of compressed gas.
· There is no reservoir system.
· Compressed gas is always filled with greater proportion.
· Gases insoluble in the product e.g. nitrogen expel in the same foam as in container.
· Gases soluble in product e.g. CO2 expel the product in the form of spray & foam.
4. Prevalve System:
This system meant for when propellant and product concentrate is incompatible and is required to be separated from each other during storage.
AEROSOL FILLING
There are two methods for aerosol filling
1. Cold Filling Method
2. Pressure Filling Method
1. Cold Filling Method:
This system is useful for non-aqueous system.
i) In this method both product concentrate and the propellant are cooled to the temperature -30°F to -40°F
ii) After cooling the product/propellant they are added to equally cold container.
2. Pressure Filling Method:
i) In this method, the product concentrate is placed quantitatively in container, then valve assembly is inserted and crimped into the placed and liquefied gas under pressure is metered into the valve system by depressing it, from a pressure burette.
ii) This method is preferred on cold filling due to
· High speed
· Less lose of propellant
· Less danger of moisture contamination
PACKAGING
· A unique aspect about the aerosol is that product is actually packaged as part of manufacturing.
· They have protective cap or cover which fit snugly over the valve and mounting cup. This protects the valve against contamination with dust and dirt. The cap, which is generally formed of plastic or metal, also serves a decorative function.
LABELING
· Labels are of usually plastic peel away labels
· Easily removed paper labels.
STORAGE
· Not to puncture the pressurized container,
· Not to store or use them near heat or open flame
· Not to incinerate them
PROPER ADMINISTRATION
i) To educate the patient about the aerosol dosage form, particularly for nasal and oral uses.
ii) To compliment verbal instructions pharmacist should provide the patient with the written instructions in the product package.
iii) Spacers or extender devices should also be provided with product package.
TYPES OF AEROSOLS
There are two main types of aerosols,
· Non-pharmaceutical Aerosols
· Pharmaceutical Aerosols
a) Non-pharmaceutical Aerosols:
· Shaving gels & foams.
· Cosmetics
· Perfumes
· Air fresheners
· Space insecticides
b) Pharmaceutical Aerosols
· Topical aerosols for on the skin include the anti infective agents
· Vaginal & Rectal Aerosols containing estrogenic substances and contraceptive agents are commercial available.
· Inhalers, which include metered dose inhalers, dry powder in halers and nebulizers.
ADVANTAGES:
· Removal of a single dose without contamination of the remaining contents of the system.
· Stability of contents with respect to O2, CO2 moisture etc.
· Ease of delivery with single push of button.
· No chance of back flow.
· No rubbing is required.
· Medicaments can be easily spread in the most of the most of the effected layer.
· Convenience, speed and ease of application.
· Immediate local application and effect.
· Controlled and uniform dosage produced by metered valves.
· Insufflation of pressurized powders is available.
· No contamination by microorganisms even when valve is opened for spray.
· It is clean process no need of washing after operation.
· Being opaque, aerosol container protects the product from light.
· Contact irritation can be minimized by aerosol system.
DISADVANTAGES:
· High cost because container, valve, propellant and filling methods are more expansive than traditional packs.
· Disposal of exhausted aerosol packs may be difficult.
· Protection from heat is necessary otherwise bursting may occur.
· Refrigeration effect of propellant may cause problems.
· Toxicity of propellant may cause problems.
· It is necessary to test the formulation against all parts of container.
