Definition of aerosol: An aerosol can be defined as a dispersion of solid and liquid particles suspended in gas.

Atmospheric aerosols, unsurprisingly, refer to solid and liquid particles suspended in air. Aerosols are produced by dozens of different processes Definition of aerosol packaging:

History of aerosols:

Back in World War II, American soldiers were fighting for their lives. They were also being eaten alive by mosquitoes. They needed a way to protect themselves. Scientists turned to a technology that had actually been around since the 18th century, but needed some modifications. Since then, step-bystep, aerosol technology has evolved to what we use today.

The Evolution of the Aerosol Product

During the 18th century, the European Enlightenment, European thinkers took notice of the mists and vapors that clouded the earth. They began to question how liquid turned to gas and back again. Natural instances of this transformation include fog, dew, and even clouds. Those are now called atmospheric aerosols, though the term aerosol wasnt coined until after WWI. If we follow our modern aerosol technology back to its humble beginnings in the late 1790s, we find 18th century French confectioners creating the first selfpressurized carbonated beverages. This means, essentially, that they figured out how to get the bubbles into a soda pop bottle. Then, in 1825, a man named Charlie Plinth invented The Regency Portable Fountain, the first portable dispenser for soda water. Think of the old-time comedians who would squirt seltzer at people. That was a version of the

Regency Portable Fountain. In 1899, a pair of inventors named Helbling & Pertsch developed a method of pressurized aerosol delivery using gases as propellants. In 1927, a Norwegian man named Erik Rotheim patented an aerosol can designed specifically for dispensing different products and fluids using the chemical propellant system.

Aerosol Fights On The Front Lines

Finally, we arrive at World War II, when American soldiers were battling pesky insects as well as enemy soldiers. In 1943, two American scientists from the Department of Agriculture, Lyle David Goodhue and W.N. Sullivan, modified Rotheims design to create an easily portable and dispensable insect repellent. They used a fluorocarbon (liquefied gas) as the propellant. The aerosol insect repellent was a relief, but sometimes the tubes and nozzles would become clogged. Plus, the soldiers small insect repellent containers somewhat resembled hand grenades-imagine the confusion that might have caused. Still, the aerosol technology was a huge relief for the itchy soldiers in the fields and jungles. In 1950, the technology was further modified by an innovative inventor named Robert H. Abplanalp. Abplanalps spray valve was clog-free. His modification kicked aerosol technology into high gear, as hair sprays, bug sprays, spray paints, and all sorts of aerosol products hit the market. The new valve design and propellant fluorocarbons proved to be a success. Aerosol technology remained pretty much the same from the 1950s into the 1970s, until the Nobel Prize winning scientist Dr. F. Sherwood Rowland and his colleague Dr. Mario Molina developed a theory that CFCs, the chlorofluorocarbon chemical propellant used in aerosol products, were depleting the Ozone layer. The Ozone layer is our main protection against the suns dangerous radioactive Ultraviolet rays, which are filtered through the stratospheric layer of reactive oxygen before they reach the Earths surface.

Saving The Planet: Aerosol Technology Evolves Again

Upon hearing the news, the aerosol industry immediately began to find new chemicals to use as propellants, replacing the dangerous CFCs. By 1978, when the U.S. Environmental Protection Agency officially banned the use of CFCs in consumer aerosol products, most had already been CFC-free for several years. Since then, other countries have followed suit, ceasing the use of CFCs and other Ozone Depleting Chemicals in their consumer and industrial technology. The Montreal Protocol of 1987 was a landmark agreement between 24 countries, each of which agreed to eventually completely discontinue the use of known ODCs.

Some CFCs are still in use, but only out of extreme necessity and when there is no other alternative. For example, some types of asthma inhalers are exempt from the ban until proper alternative propellants can be found. Until then, it is a small price to pay to help asthma patients breathe easy. The overwhelming majority of aerosol technology is now completely CFC-free, and completely environmentally friendly. So, next time you reach for the bug spray on a summer day, or go to the salon to have your hair styled, remember that the aerosol technology you are benefiting from has been safe for decades. Introduction to aerosol packaging

Aerosols are unique among the pharmaceutical dosage forms because they depend on the function of a container, its valve assembly, and propellants for the physical delivery of the ingredients. The aerosol container is referred to as a pressurized package. The pressure inside the package is created by the presence of one or more liquefied or gaseous propellants. When the valve is actuated (i.e., opened), the pressure forces the contents of the package out through the opening in the valve. The physical form of the expelled contents is a function of the product formulation and the type of valve employed.

Aerosols used to provide an airborne mist are called space sprays and include room disinfectants and deodorizers. This group of aerosols produce particles that are usually less than 50 m in size. This will ensure that the dispersed droplets or particles will remain airborne for a prolonged period of time. A one second burst from a typical space spray will produce 120 million particles in which a substantial number will remain airborne for an hour. Aerosols intended to carry the active drug to a surface are called surface sprays or

surface coating sprays. This class of sprays includes products such as deodorant sprays, hair sprays, perfume and cologne sprays, shaving lathers, paint sprays, and various household products such as spray starch, waxes, polishes, and cleaners.

Comparison of Space Sprays and Surface Spray

Property Product Concentrate (%) Propellant (%) Pressure (psig at 70oF) Particles ( m) Space Spray 2 20 80 98 30 40 <1 50 Surface Spray 20 - 75 25 - 80 25 - 55 50 - 200

Pharmaceutical aerosols emit liquid or solid materials in a gaseous medium when they are actuated. The contents may be a fine mist, a course wet or dry spray, a steady stream, or a fast breaking foam. Pharmaceutical aerosols are intended to deliver active drugs for inhalation, nasal, buccal, and sublingual administration. Aerosols are also available for topical, rectal, and vaginal administration. Some general advantages of pharmaceutical aerosols include: 1. Aerosols are easy to use. Medication is dispensed at the push of a button. No ancillary equipment is needed. 2. Aerosol application is a clean process which requires minimal patient "clean up" after using the product. 3. A portion of medication may be easily withdrawn without contaminating the remaining material. If the product is sterile, sterility can be maintained throughout the product's shelf life. 4. The active drug is protected from oxygen and moisture. The usual aerosol container is opaque which also protects the drug from light. 5. By proper formulation and valve control, the physical form and the particle size of the emitted product may be controlled. 6. If the dosage must be regulated, a metered dose valve can be used which will control the accuracy of the administered dose. Many pharmaceutical aerosols are used for oral (i.e., buccal and sublingual), nasal, or inhalation administration of vaccines, antiviral compounds, and hormones. These aerosols provide the advantage of a rapid onset of action and avoid the first pass effect and gastrointestinal tract degradation. In some cases, lower drug dosages can be used which has the additional benefit of minimizing adverse reactions. Using these routes also provides a viable alternative for administration of drugs that exhibit erratic pharmacokinetics after oral or parenteral administration.

Other pharmaceutical aerosols are used for topical, vaginal, and rectal administration. Topical medications can be applied as a spray, foam, or semisolid in a uniform thin layer without having to touch or mechanically irritate the affected area. The use of an aerosol will also limit the potential for overuse of a product compared to lotions, creams, and ointments. For vaginal and rectal applications, aerosols can be delivered as an expanding foam to ensure a direct and extensive contact between the drug and the mucosa.

Aerosol packaging:
The Valve Assembly The effectiveness of a pharmaceutical aerosol depends on achieving the proper combination of product concentrate formulation, container, and valve assembly. The valve mechanism is the part of the product package through which the contents of the container are emitted. The valve must withstand the pressure required by the product concentrate and the container, be corrosive resistant, and must contribute to the form of the emitted product concentrate. The primary purpose of the valve is to regulate the flow of product concentrate from the container. But the valve must also be multifunctional and regulate the amount of emitted material (metered valves), be capable of delivering the product concentrate in the desired form, and be easy to turn on and off. Among the materials used in the manufacture of the various valve parts are plastic, rubber, aluminum, and stainless steel. Figure 17-3 The basic parts of a valve assembly can be described as: 1. Actuator - the actuator is the button which the user presses to activate the valve assembly and provides an easy mechanism of turning the valve on and off. In some actuators, mechanical breakup devices are also included. It is the combination of the type and quantity of propellant used and the actuator design and dimensions that determine the physical form of the emitted product concentrate. 2. Stem - the stem supports the actuator and delivers the formulation in the proper form to the chamber of the actuator. 3. Gasket - the gasket, placed snugly with the stem, serves to prevent leakage of the formulation of the valve is in the closed position. 4. Spring - the spring holds the gasket in place and also is the mechanism by which the actuator retracts when pressure is released thereby returning the valve to the closed position. 5. Mounting Cup - the mounting cup which is attached to the aerosol container serves to hold the valve in place. Because the undersigned of the mounting cup is exposed to the formulation, it must receive the same consideration as the inner part of the container with respect to meeting criteria of compatibility. If necessary, it may be coated with an inert material to prevent an undesired interaction. 6. Housing - the housing located directly below the mounting cup serves as the link between the dip tube and the stem and actuator. With the stem, its orifice helps to determine the delivery rate and the form in which the product is emitted.

7. Dip Tube - the dip tube which extends from the housing down into the product concentrate serves to bring the formulation from the container to the valve. The viscosity of the product and its intended delivery to rate dictate the inner dimensions of the dip tube and housing for a particular product. Spray valves are used to obtain fine to coarse wet sprays. Depending on the formulation and the design of the valve and actuator, the particle size of the emitted spray can be varied. The spray is produced as an aerosol solution passes through a series of small orifices which open into chambers that allow the product concentrate to expand into the proper particle size. Vapor tap valves are used with powder aerosols, water based aerosols, aerosols containing suspended materials, and other agents that would tend to clog a standard valve. This valve is basically a standard valve except that a small hole has been placed into the valve housing. This allows vaporized propellant to be emitted along with the product concentrate and produces a spray with greater dispersion. These valves are used with aqueous and hydroalcoholic product concentrates and hydrocarbon propellants. Foam valves have only one orifice that leads to a single expansion chamber. The expansion chamber also serves as the delivery nozzle or applicator. The chamber is the appropriate volume to allow the product concentrate to expand into a ball of foam. Foam valves are used for viscous product concentrates such as creams and ointments because of the large orifice and chamber. Foam valves also are used to dispense rectal and vaginal foams. If the size of the orifice and expansion chamber are appropriately reduced, a product concentrate that would produce a foam will be emitted as a solid stream. In this case, the ball of foam begins to develop where the stream impinges on a surface. Metered dose inhaler (MDI) valves (metering values) are used to accurately deliver a dose of medication. Metered valves are used for all oral, inhalation, and nasal aerosols. The metered valves reproducibly deliver an amount of product concentrate accurately from the same package and also allow for the same accuracy between different packages. Figure 17-4 The amount of material emitted is regulated by an auxiliary valve chamber of fixed capacity and dimensions. This metering chamber volume can be varied so that about 25 to 150 l of product concentrate is delivered per actuation. Access in and out of the metering chamber is controlled by a dual valve mechanism. When the actuator is closed, a seal blocks emission from the chamber to the atmosphere. However, the chamber is open to the contents of the container and it is filled. When the actuator is depressed, the seals reverse function; the chamber becomes open to the atmosphere and releases its contents and at the same time becomes sealed from the contents of the container. When the actuator is again closed, the system prepares for the next dose. Two basic types of metering valves are available; one for inverted use and the other for upright use. Generally the valves for upright use are used with solution type aerosols and contain a thin capillary dip tube. Suspension or dispersion aerosols use the valve intended for inverted use that does not contain a dip tube. In general, valves should retain the material in the metering chamber for fairly long periods. However, it is possible for the material in the chamber to slowly return back to the container. The degree to

which this occurs depends on the construction of the valve and length of time between actuations of the valves. Some valves have been fitted with a "drain tank" to overcome this problem. Figure 17-5 Containers Aerosol containers are generally made of glass, metals (e.g., tin plated steel, aluminum, and stainless steel), and plastics. The selection of the container for a particular aerosol product is based on its adaptability to production methods, compatibility with the formulation, ability to sustain the pressure necessary for the product, the design and aesthetic appeal, and the cost. Pressure Limitations of Aerosol Containers

Container Material
Tin-plated steel Uncoated glass Coated glass Aluminum Stainless Steel Plastic

Maximum Pressure (psig)

180 < 18 < 25 180 180 < 25

Temperature (oF)

130 70 70 130 130 70

Glass containers would be the preferred container for most aerosols. Glass presents fewer problems with respect to chemical compatibility with the formulation compared to metal containers and is not subject to corrosion. Glass is also more adaptive to design creativity and allows the user to view the level of contents in the container. However, glass containers must be precisely engineered to provide the maximum pressure safety and impact resistance. Therefore, glass containers are used in products that have lower pressures and lower percentages of propellants. When the pressure is below 25 psig and less than 50% propellant is used, coated glass containers are considered safe. To increase the resistance to breakage, plastic coatings are commonly applied to the outer surface of glass containers. These plastic coatings serve many purposes: 1) prevent the glass from shattering into fragments if broken; 2) absorb shock from the crimping operation during production thus decreasing the danger of breakage around the neck; 3) protect the contents from ultraviolet light; 4) act as a means of identification since the coatings are available in various colors.

Glass containers range in size from 15 to 30 ml and are used primarily with solution aerosols. Glass containers are generally not used with suspension aerosols because the visibility of the suspended particles presents an aesthetic problem. All commercially available containers have a 20 mm neck finish which adapts easily to metered valves. Tin-plated steel containers are light weight and relatively inexpensive. For some products the tin provides all the necessary protection. However when required, special protective coatings are applied to the tin sheets prior to fabrication so that the inside of the container will be protected from corrosion and interaction between the tin and the formulation. The coating usually is an oleoresin, phenolic, vinyl, or epoxy coating. The tin plated steel containers are used in topical aerosols. Aluminum is used in most MDIs and many topical aerosols. This material is extremely light weight and is less reactive than other metals. Aluminum containers can coated with epoxy, vinyl, or phenolic resins to decrease the interaction between the aluminum and the formulation. The aluminum can also be anodized to form a stable coating of aluminum oxide. Most aluminum containers are manufactured by an impact extrusion process that make them seamless. Therefore, they have a greater safety against leakage, incompatibility, and corrosion. Aluminum containers are made with a 20 mm neck finish that adapts to the metered valves. For special purposes and applications, containers are also available that have neck finishes ranging from 15 to 20 mm. The container themselves available in sizes ranging from 10 ml to over 1,000 ml. Stainless steel is used when the container must be chemically resistant to the product concentrate. The main limitation of these containers is their high cost. Plastic containers have had limited success because of their inherent permeability problems to the vapor phase inside the container. Also, some drug-plastic interactions have limited the efficacy of the product.

Aerosol system:
When liquefied gases (CFC, HCFC, HFC, hydrocarbons) are used as propellants, one of two systems can be formulated. The two phase system is the simplest system. Here the product concentrate is dissolved or dispersed in liquefied propellant and solvents creating a homogenous system. The propellants exist in both the liquefied phase and the vapor phase. When the aerosol valve is actuated, some liquefied propellant and solvent containing the product concentrate is emitted from the container. These aerosols are designed to produce a fine mist or wet spray by taking advantage of the large expansion of the propellant when it enters room temperature and atmospheric pressure. The two phase system is commonly used to formulate aerosols for inhalation or nasal application. A three phase system (i.e., a heterogeneous system) is made up a layer of water immiscible liquid propellant, a layer of propellant immiscible liquid (usually water) which contains the product concentrate, and the vapor phase. This type of system is used when the formulation requires the presence of a liquid phase that is not propellant miscible. When the aerosol valve is actuated, the pressure of the vapor phase causes the liquid phase to rise in the dip tube and be expelled from the container. If the product is to maintain the liquefied gas reservoir, the dip tube must not extend beyond the aqueous phase. Sometimes it is desirable to have some liquefied propellant mixed with the

aqueous phase to facilitate in the dispersion of the spray or to create a foam. In this case, the container should be shaken immediately prior to use. If CFCs, HCFCs, and HFCs are used as the propellants, they will reside on the bottom of the container since their density is greater than water. The dip tube will then need to end somewhere in the middle of the container. If hydrocarbons are used as the propellants, they will reside on the aqueous layer since their density is less than water. In this case, the dip tube can be extended through the liquid propellant all the way down to the bottom of the container. Thus an important characteristic of any aerosol is the density of the propellant, propellants, or blend of propellants. Foam aerosols are a three phase system in which the liquid propellant is emulsified with the product concentrate. When the valve is actuated, the emulsion is forced through the nozzle and the entrapped propellant reverts to the vapor phase and whips the emulsion into a foam when it reaches the atmosphere. To facilitate the formulation of a foam, some aerosols are shaken prior to use to disperse some of the propellant throughout the product concentrate. If a dip tube is present, the container is used while being held upright. If there is no dip tube, the container must be inverted prior to use. Foam products operate at a pressure of about 40 to 50 psig at 70F and contain about 4 to 7% propellant. Generally, a blend of propane and isobutane is used for foam aerosols. Contraceptive foam aerosols use A-31 as the propellant. Other foams use P-152a since it will produce a more stable foam and is less flammable than hydrocarbons. Other propellants that have been used include the compressed gases nitrous oxide and carbon dioxide. Typical products include whipped creams and toppings and several pharmaceutical and veterinary products. Aerosols using compressed gases as the propellant operate essentially as a pressure package. The pressure of the gas forces the product concentrate out of the container in essentially the same form as it was placed in the container. Only the product concentrate is expelled; the compressed gas remains in the container occupying the headspace. The pressure drops in the container as the product concentrate is removed and the gas expands to occupy the newly vacated space. The pressure will continue to drop as the product concentrate is expelled. Therefore, the initial pressure in these containers is higher than used in liquefied gas aerosols and is usually 90 to 100 psig at 70F. The amount of product left in the container after the pressure is exhausted varies with the viscosity of the product and loss of pressure due to gas seepage. Depending on the nature of the formulation and the type of compressed gas used, the product may be dispensed as a semisolid (solid stream) foam or spray. Semisolid aerosols are used to dispense more viscous concentrates such as dental creams, hair dressings, ointments, creams, cosmetic creams, and foods. In barrier pack systems, the propellant is physically separated from the product concentrate. The propellant pressure on the outside of the barrier serves only to push the contents from the container. In the piston type system, a polyethylene piston is fitted into the container. The product concentrate is placed into the upper portion of the container and a compressed gas or hydrocarbon gas is placed on the other side of the piston. The gas pushes against the piston and pushes the product concentrate out of the container when the valve is actuated. As the rises in the container, it scrapes against the side of the container which helps dispense most of the product concentrate.

Figure 17-1

This system is used to dispense cheese spreads, cake decorating icings, and ointments. Since these product concentrates are semisolid and viscous, they emit from the container as a lazy stream rather than a foam or spray. The piston type system is limited to viscous materials since liquids tend to pass around the edges of the piston into the gas compartment. A collapsible plastic bag fitted into a container is another type of barrier pack system. In some systems, the bag is a thin walled aluminum pouch. The product concentrate is placed in the bag and the propellant surrounds the bag. The bag is accordion pleaded to prevent the gas from pinching it closed. These types of systems are used to dispense liquids as fine mists or streams, and semisolids as streams. They system can also be used for topical creams, ointments, or gels. Figure 17-2 Gels that foam after being dispensed are placed in both the piston type and collapsible plastic bag type of system. The dispensed gel contains a low boiling liquid such as isopentane or pentane in it. The liquid will vaporized when the gel is placed in the warmth of the hands and this will produce the foaming gel.

Aerosol filling processes:

Two methods are used to manufacture aerosols: the cold fill process and thepressure fill process. The cold fill process takes advantage of the property that some ingredients will liquefy when cooled, and the pressure fill process uses the property that some ingredients will liquefy when placed under pressure. In the cold fill process, both the product concentrate and the propellant must be cooled to temperatures between 30C to 60C where they will remain liquefied. The cooling system may be a mixture of dry ice and acetone or a elaborate refrigeration system. The chilled product concentrate is quantitatively added to the equally cold aerosol container and then the liquefied gas is added. The heavy vapors of the cold liquid propellant will generally displace the air present in the container. When filling is complete, the valve assembly is inserted into the container and crimped into place. The container is then passed through a water bath of about 55C to check for leaks or distortion in the container. Aqueous solutions cannot be filled by this process since the water will turn to ice in the low temperatures. For nonaqueous systems, some moisture usually appears in the final product due to the condensation of atmospheric moisture within the cold containers. Pressure filling is carried out essentially at room temperature. The product concentrate is placed in the container, the valve assembly is inserted and crimped into place, and then the liquefied gas, under pressure, is added through the valve. The entrapped air in the package might be ignored if it does not interfere with the stability of the product, or it may be evacuated prior to filling or during filling. After the filling operation is complete, the valve is tested for proper function. This spray testing also rids the

dip tube of pure propellant prior to consumer use. Pressure filling is used for most pharmaceutical aerosols. It has the advantage that there is less danger of moisture contamination of the product and also less propellant is lost in the process.