Aerosol in Pharma (Aerosols); Types, Container, Advantage, and Disadvantage

A pharmaceutical aerosol is a self-pressurised pack. Its metal, glass or plastic container has a permanently attached continuous or metering valve. The valve releases the product as a spray, stream or gel. It also releases foam, lotion or gas. Approximately 90% of aerosol cans are tinplated steel and 10% aluminum.

An aerosol is a suspension of fine solid particles or liquid droplets in a pressurised gas. Suspension aerosols for the respiratory tract need a particle size of 1-5 micrometers. No particle should be larger than 10 micrometers. A dispensing device that produces an aerosol mist of liquid particles is known as an aerosol spray.

Working of Aerosol in Pharma

An aerosol works through a container that holds a liquid under pressure and a valve that releases it as a fine mist. The propellant provides the pressure. Its type decides the product that can be dispensed (see also Liquid Dosage Form).

An aerosol spray works with a can or bottle that contains a liquid under pressure. When the valve of the container is opened, the liquid is driven out of a small hole and emerges as an aerosol or mist. As the gas expands to drive out the payload (the product that is dispensed), some propellant evaporates inside the can to maintain an even pressure. Outside the can, the droplets of propellant evaporate rapidly, and the payload remains suspended as very fine particles or droplets. Insecticides, deodorants and paints are typical liquids dispensed in this way. An atomizer is a similar device, but it is pressurised by a hand-operated pump rather than by stored gas.

Usually, the gas is the vapour of a liquid with a boiling point slightly lower than room temperature. Inside the pressurised can, the vapour stays in equilibrium with its bulk liquid. The pressure is higher than atmospheric pressure, so it can expel the payload. It is not dangerously high.

The escaping gas is quickly replaced by evaporating liquid. Because the propellant is liquid in the can, it should be miscible with the payload or dissolved in it.

Chlorofluorocarbons (CFCs) are organic compounds that contain carbon, chlorine and fluorine. The Montreal Protocol phased out CFC propellants because they damage the ozone layer; hydrocarbons and hydrofluoroalkanes (HFA 134a, HFA 227) replaced them. The most popular substitutes are volatile hydrocarbon mixtures, such as propane, n-butane and isobutane. Dimethyl ether (DME) and methyl ethyl ether are also used. All of these are flammable.

Food is also delivered using nitrous oxide and carbon dioxide as propellants (for example, whipped cream and cooking spray). Medicinal aerosols such as asthma inhalers use hydrofluoroalkanes (HFA). One is HFA 134a (1,1,1,2-tetrafluoromethane). The other is HFA 227 (1,1,1,2,3,3,3-heptafluoropropane). Combinations of the two are also used.

For more detail on aerosol propellants in pharmaceuticals, see Aerosol Propellants in Pharmaceuticals: CFC Replacement, Hydrocarbons, DME and HFA.

Components of Aerosols Container

The container of an aerosol consists of the following components. Details of container materials are given in Pharmaceutical Packaging.

a. Propellants: The propellant is either a liquefied gas or a compressed gas.

b. Containers: Containers are generally made of tinplated steel and aluminum.

c. Dip tube: The dip tube is made of polyethylene and polypropylene.

d. Valve and actuator: The valve contains a ferrule or mounting cap, a valve body, a dip tube and metering valves.

• The ferrule joins the valve properly to the container.

• The valve body has an opening for attachment of the dip tube. It contains a vapour tab, which produces fine particle size and prevents clogging of the valve.

For more deatils read: Aerosol Valve, Actuator and Dip Tube: Components and Their Functions.

For more detail on suspension aerosols, see Suspension Aerosols: Particle Size, Oleic Acid and Valve Clogging.

Types of Aerosol Systems

Aerosol systems are classified as two-phase or three-phase systems, depending on how the active ingredients are held with the propellant.

Two-phase system: In a two-phase system, the first phase is the propellant (or its mixture) with the active ingredients. The active ingredients dissolve either in a solvent that is soluble in the propellant, or directly in the propellant. The second phase is the vapour of the propellant.

Foams generally use 5% propellant, and inhalation products use 95% propellant.

Oleic acid is used as a suspending agent to stop suspended particles from settling and clumping together. Clumps can clog the valve and cause an error in the dose.

Three-phase system: A three-phase system is used for topical products whose active ingredients do not dissolve in the propellant. Another solvent is used instead, and this solution forms the first phase. The liquid propellant is the second phase, because the solution is immiscible with it. The vapour phase is the third phase. Water-based aerosols involve three-phase systems.

Foam dispensing aerosols: These use CO2 and N2O.

A separate guide explains two-phase and three-phase aerosol systems: Two-Phase vs Three-Phase Aerosol Systems: Formulation Guide.

Manufacturing of Aerosols

Aerosols are filled by cold filling or pressure filling. Schedule M requires aerosol filling and manufacturing to follow written, validated procedures in controlled premises.

Cold filling: Cold filling is done at a low temperature, typically about -34 to -40 °C (-30 to -40 °F), to which the concentrate, the propellant and the container are chilled. The range varies by manufacturer. It is not suitable for aqueous products or temperature-sensitive preparations.

Pressure filling: Pressure filling is used for all types of aerosols.

Quality control test for pharmaceutical aerosols:

The quality control tests cover flammability, particle size, propellant identity, foam stability, dosage, pressure, density, moisture and valve performance. USP general chapter <601> (Aerosols, Nasal Sprays, Metered-Dose Inhalers and Dry Powder Inhalers) sets the performance tests for inhalation aerosols. These include particle size by cascade impaction and delivered dose.

1. Flame projection test and Flashpoint test (using the Pensky-Martens/Tag open cup apparatus): for flammability and combustibility.
2. Particle size determination: By using a cascade impactor and light scattering decay.
3. Identification of propellants: By gas chromatography and refractive index.
4. Foam stability: Visual evaluation, and the time for a mass to penetrate the foam, using a rotational viscometer.
5. Dosage with metered valve: From the reproducibility of dosage each time the valve is pressed.
6. Vapour pressure: It is measured by a pressure gauge.
7. Density: It is measured by a pycnometer or hydrometer.
8. Moisture content: It is measured by the Karl Fischer method.
9. Performance: Valve discharge rate.

A separate guide explains quality control tests for pharmaceutical aerosols: Quality Control Tests for Pharmaceutical Aerosols: Methods and Apparatus.

For more detail on aerosol particle size measurement, see Aerosol Particle Size Measurement: Cascade Impactor and Light Scattering Decay.

Advantages of Aerosol

The advantages of aerosol relate to the delivery of the drug to the affected area, ease of use and protection of the medicine.

• Contamination of the materials is reduced, because the product is used directly in affected areas.
• The amount of drug can be delivered directly to affected organs in the desired form.
• The product is easy to use without any mixing of external components.
• Aerosol administration provides immediate and effective relief.
• Stability improves, because metered-dose inhalers (MDIs) and dry powder inhalers (DPIs) keep the medicine away from ambient oxygen and moisture.
• Aerosol medication administration is a quick process.
• The medication is protected against breakdown in the gastrointestinal tract.
• Hepatic first-pass metabolism can be avoided.
• Aerosols can be used for systemic and local purposes.

Related Searches: Gels in Pharmaceuticals

Cold Filling vs Pressure Filling of Pharmaceutical Aerosols covers cold filling and pressure filling aerosols in more detail.

Disadvantages of Aerosol

The disadvantages of aerosol relate to cost, disposal, safety and manufacturing difficulty.

• The dosage form is costly.
• Empty containers are difficult to discard.
• Allergic reactions may occur in some cases.
• It may cause an explosion.
• Aerosol dosage forms of insoluble drugs are challenging to manufacture.
• Propellants can create a harmful reaction in some cases.
• The product may be contaminated in some cases by trace metals present in the container.

FAQs

References

• Schedule M, CDSCO, Drugs Rules, 1945
• USP, United States Pharmacopeia (USP–NF)