The Pharmaceutics and Compounding Laboratory

An aerosol formulation consists of two components: the product concentrate and the propellant. The product concentrate is the active drug combined with additional ingredients or co-solvents required to make a stable and efficacious product. The concentrate can be a solution, suspension, emulsion, semisolid, or powder. The propellant provides the force that expels the product concentrate from the container and additionally is responsible for the delivery of the formulation in the proper form (i.e., spray, foam, semisolid). When the propellant is a liquefied gas or a mixture of liquefied gases, it can also serve as the solvent or vehicle for the product concentrate. If the product characteristics are to change on dispensing, additional energy in the form of a mechanical breakup system may be required.


A propellant is a chemical with a vapor pressure greater than atmospheric pressure at 40°C (105°F). Types of propellants commonly used in pharmaceutical aerosols include chlorofluorocarbons, hydrocarbons, hydrochlorofluorocarbons and hydrofluorocarbons, and compressed gases.

Chlorofluorocarbon (CFC) propellants

For many years, the chlorofluorocarbon (CFC) propellants P-11, P-12, and P-114 were used in aerosol products. Their use has been severely curtailed due to their role in depleting the ozone layer of the atmosphere. Since January 1996, worldwide production of these CFCs has been reduced to only the amount needed for aerosols used in the treatment of asthma and chronic obstructive pulmonary disease. Alternatives to P-12 (i.e., P-134a and P-227) have now been developed and are being incorporated in aerosol formulations. Currently, there are not alternatives for P-11 and P-114. Small amounts of P-11 are required in most aerosol suspensions to make a slurry of the active drug and other ingredients. It also is used to dissolve surfactants in some formulations.

P-11, P-12, and P-114 are the CFCs of choice for oral, nasal, and inhalation aerosols. These particular chlorofluorocarbon propellants are well accepted due to their relatively low toxicity and inflammability. The chlorofluorocarbons as a class are inert but P-11 is subject to hydrolysis and will form hydrochloric acid in the presence of water. The acid increases the corrosion of the container and may be irritating when applied to membranes. If water is present, P-12 or a mixture of P-12 and P-114 are used.

The CFCs are gases at room temperature that can be liquefied by cooling them below their boiling point or by compressing them at room temperature. For example, dichlorodifluoromethane (P-12) will form a liquid when cooled to -21.6°F or when compressed to 84.9 psia at 70°F (psia = pounds per square inch absolute). These liquefied gases also have a very large expansion ratio compared to the compressed gases (e.g., nitrogen, carbon dioxide). The usual expansion ratio for liquefied gases is about 1 to 240 which means that 1 mL of liquefied gas will occupy a volume of approximately 240 mL if allowed to vaporize. Compressed gases have an expansion ratio of about 3 to 10.

Properties of Chlorofluorocarbon Propellants

Name Formula No. V.P.
@70°F (psia)a
°F (1 atm)
Liquid Density
@70°F (g/mL)



















apsia (pounds per square inch absolute) = psig (pounds per square inch gauge + 14.7)

The numerical designations for fluorinated hydrocarbons propellants have been designed so the chemical structure of the compound can be determined from the number. The system consists of three digits.

  • The digit at the extreme right refers to the number of fluorine atoms in the molecule.
  • The second digit from the right represent one greater in the number of hydrogen atoms in the molecule.
  • The third digit from the right is one less than the number of carbon atoms in the molecule; if this third digit is 0, it is omitted and a two-digit number is used.
  • The capital letter "C" is used before a number to indicate the cyclic nature of a compound.
  • The small letters following a number are used to indicate decreasing symmetry of isomeric compounds. The most symmetrical compound is given the designated number, and all other isomers are assigned a letter (i.e., a, b, etc.) in descending order of symmetry.
  • The number of chlorine atoms in a molecule may be determined by subtracting the total number of hydrogen and fluorine atoms from the total number of atoms required to saturate the compound.

When a liquefied gas propellant or propellant mixture is sealed in an aerosol container with the product concentrate, an equilibrium is establish between the propellant which remains liquefied and a portion that vaporizes and occupies the upper portion of the container. The pressure at this equilibrium is referred to as the vapor pressure (expressed as psia) and is a characteristic of each propellant at a given temperature. Since the vapor pressure is exerted equally in all directions and is independent of the quantity of liquefied phase present, the pressure forces the liquid phase up the dip tube and out of the container when the valve is actuated. As the propellant reaches the air, it evaporates due to the drop in pressure and leaves the product concentrate as airborne liquid droplets or dry particles. As the liquid is removed from the container through the dip tube, the equilibrium between the propellant's liquefied phase and vapor phase is rapidly re-established. Thus, the pressure within the container remains virtually constant and the product may be continuously released at an even rate and with the same propulsion.

In the case when there is no dip tube in the container, the container is used in the inverted position so that the liquid phase will be in direct contact with the valve. When the valve is actuated, the liquid phase is emitted and immediately reverts to the vapor phase in the atmosphere.

Hydrochlorofluorocarbons (HCFC) and Hydrofluorocarbons (HFC)

The hydrochlorofluorocarbons (HCFC) and hydrofluorocarbons (HFC) differ from CFCs in that they may not contain chlorine and have one or more hydrogen atoms. These compounds break down in the atmosphere at a faster rate than the CFCs resulting in a lower ozone depleting effect.

P-22, 142b, and 152a are used in topical pharmaceuticals. These three propellants have a greater miscibility with water and therefore are more useful as solvents compared to the other propellants. They are also slightly more flammable than the other propellants but this is not perceived as a disadvantage.

Properties of Hydrochlorofluorocarbon and Hydrofluorocarbon Propellants

Name Formula No. V.P.
@70°F (psia)
°F (1 atm)
Liquid Density
@70°F (g/mL)
































The hydrocarbons are used in topical pharmaceutical aerosols because of their environmental acceptance and their low toxicity and nonreactivity. They are also useful in making three phase (two layer) aerosols because of their density being less than 1 and their immiscibility with water. The hydrocarbons remain on top of the aqueous layer and provide the force to push the contents out of the container. However, they are flammable and can explode. They contain no halogens and therefore hydrolysis does not occur making these good propellants for water based aerosols.

Properties of Hydrocarbon Propellants

Name Formula No. V.P.
@70°F (psia)
°F (1 atm)
Liquid Density
@68°F (g/mL)



















Propane, butane, and isobutane are the most commonly used hydrocarbons. They are used alone or as mixtures or mixed with other liquefied gases to obtain the desired vapor pressure, density, and degree of flammability. The flammability hazard has been substantially reduced by using mixtures of propellants and with the development of newer types of dispensing valves (i.e., valve with vapor tap).

Compressed Gases

Gases such as nitrogen, nitrous oxide, and carbon dioxide have been used as aerosol propellants for products dispensed as fine mists, foams, or semisolids. But due to their low expansion ratio, the sprays are fairly wet and the foams are not as stable as produced by liquefied gas propellants. However, using a compressed gas that is insoluble in the product concentrate (e.g., nitrogen) will emit the product concentrate in essentially the same form as it was placed in the container.

The pressure of the compressed gas contained in the headspace of the aerosol container forces the product concentrate out of the container. But unlike aerosols prepared with liquefied gas propellants, there is no propellant reservoir. So higher gas pressures are required in these aerosols and the pressure diminishes as the product is used. These gases have been used for the most part to dispense food products, dental creams, hair preparations, and ointments.

Properties of Compressed Gases

Name Formula V.P.
@70°F (psia)
°F (1 atm)
Gas Density
@70°F (g/mL)






Nitrous Oxide





Carbon Dioxide






Product Concentrates

Solution aerosols are two phase systems consisting of the product concentrate in a propellant, a mixture of propellants, or a mixture of propellant and solvent. Solvents may also be added to the formulation to retard the evaporation of the propellant. Solution aerosols can be difficult to formulate because many propellant or propellant-solvent mixtures are nonpolar and are poor solvents for the product concentrate. Also, there is a limited number of solvents that can be used. Ethyl alcohol is the most commonly used solvent but propylene glycol, dipropylene glycol, ethyl acetate, hexylene glycol, and acetone have also been used.

Aerosol solutions have been used to make foot preparations, local anesthetics, spray-on protective films, anti-inflammatory preparations, and aerosols for oral and nasal applications. They contain 50 to 90% propellant for topical aerosols and up to 99.5% propellant for oral and nasal aerosols. As the percentage of propellant increases, so does the degree of dispersion and the finest of the spray. As the percentage of propellant decreases, the wetness of the spray will increase. The particle sizes of the sprays can vary from 5 to 10μm in inhalation aerosols and 50 to 100 μm for topical sprays.

Suspensions aerosols can be made when the product concentrate is insoluble in the propellant or mixture of propellant and solvent, or when a co-solvent is not desirable. Anti-asthmatic drugs, steroids, and antibiotics are delivered as suspension aerosols. When the valve is actuated, the suspension formulation is emitted as an aerosol and the propellant rapidly vaporizes and leaves a fine dispersion of the product concentrate.

Formulation considerations for suspension aerosols, not necessary with solution aerosols, include agglomeration, particle size growth, valve clogging, moisture content, and particle size of the dispersed aerosolized particles. Lubricants such as isopropyl myristate and light mineral oil, and surfactants such as sorbitan trioleate, oleic acid, and lecithin have been used to overcome the difficulties of particle size agglomeration and growth which are directly related to the clogging problems. The moisture content of the entire formulation should be kept below 200 to 300 ppm so all of the ingredients need to be the anhydrous form of the chemical or be capable of becoming anhydrous after a drying process. The particle size of the insoluble product concentrate ingredients should be in the 1 to 10 µm range for inhalation aerosols and between 40 to 50 µm for topical aerosols.

The product concentrate in an emulsion aerosol will consist of the active ingredient, aqueous and/or nonaqueous vehicles, and a surfactant. Depending on the components, the emitted product can be a stable foam (shaving cream type) or a quick breaking foam. A quick breaking foam creates a foam when emitted from the container but the foam collapses in a relatively short time. This type of foam is used to apply the product concentrate to a large area without having to manually rub or spread the product. Also, the active drug is more rapidly available because the foam quickly collapses.

Foams are produced when the product concentrate is dispersed throughout the propellant and the propellant is in the internal phase; i.e., the emulsion behaves like o/w emulsions. When the propellant is in the external phase (i.e., like a w/o emulsion), foams are not created but sprays or wet streams result. Stable foams are produced when surfactants are used that have limited solubility in both the organic and aqueous phases. Surfactants concentrate at the interface between the propellant and the aqueous phase forming a thin film referred to as the "lamella." It is the specific composition of this lamella that dictates the structural strength and general characteristics of the foam. Thick and tightly layered lamellae produce very structured foams which are capable of supporting their own weight.

Surfactants used in emulsion aerosols have included fatty acids saponified with triethanolamine, anionic surfactants, and more recently nonionic surfactants such as the polyoxyethylene fatty esters, polyoxyethylene sorbitan esters, alkyl phenoxy ethanols, and alkanolamides. The nonionic surfactants are present fewer compatibility problems because they charge no electronic charge.