Pharmaceutical Aerosols: Definition and general introduction and MCQs for GPAT, NIPER, Pharmacist and Drug Inspector exam
Pharmaceutical Aerosols
Inhalation therapy has been used for many years, and there has been a resurgence of interest in delivery of drugs by this route of administration. The number of new drug entities delivered by the inhalation route has increased over the past five to ten years. This type of therapy also has been applied to delivery of drugs through the nasal mucosa, as well as through the oral cavity for buccal absorption.
Drugs administered via the respiratory system (inhalation therapy) can be delivered either orally or nasally. Further, these products can be developed as a
- nebulizer/atomizer
- dry powder inhaler
- nasal inhaler
- metered-dose aerosol inhaler
Advantages of Aerosols-
• Rapid onset of action.
• Circumvention of the first-pass effect and avoidance of degradation in the GI tract.
• Lower dosage that will minimize adverse reactions, especially in the case of steroid therapy, in which most of the steroid reaches the respiratory tract and less is swallowed.
• Dose titration to individual needs and ideal for prn medication.
• Alternative route when therapeutic agent may interact chemically or physically with other medicinals needed concurrently.
• Viable alternative when the drug entity exhibits erratic pharmacokinetics upon oral or parenteral administration.
• Container and valve closure are tamperproof.
Definition: The term aerosol is used to denote various systems ranging from those of a colloidal nature to systems consisting of pressurized packages. Aerosols have been defined as colloidal systems consisting of very finely subdivided liquid or solid particles, dispersed in and surrounded by a gas. Originally, the term aerosol referred to liquid or solid particles having a specific size range, but this concept has fallen into disuse. The present-day definition refers to those products that depend upon the power of a liquefied or compressed gas to dispense the active ingredient(s) in a finely dispersed spray, foam, or semisolid. Pump systems that also dispense the active ingredient(s) in the form of a finely dispersed mist (although of greater particle size) often are classified as aerosols. These pump systems generally are used to dispense medication intranasally.
Mode of operation –
1. Liquefied-gas systems – Liquefied gases have been used widely as propellants for most aerosol products. These compounds are useful for this purpose, since they are gases at room temperature and atmospheric pressure. However, they can be liquefied easily by lowering the temperature (below the boiling point) or by increasing the pressure. The compounds chosen generally have boiling points below 70°F (21°C) and vapor pressures between 14 and 85 psia at 70°F (21°C). When a liquefied-gas propellant is placed into a sealed container, it immediately separates into a liquid and a vapor phase.
2. Two-phase system – This is the simplest of all aerosol systems. It consists of a solution or a suspension of active ingredients in liquid propellant or a mixture of liquid propellant and solvent. Both a liquid and a vapor phase are present, and when the valve is depressed, liquid propellant containing dissolved active ingredients and other solvents are released. Depending on the nature of the propellants used, the quantity of propellant present, and the valve mechanism, a fine mist or wet spray is produced because of the large expansion of the propellant at room temperature and atmospheric pressure. This system is used to formulate aerosols for inhalation or nasal application.
3. Three-phase system – This system is useful for topical pharmaceutical aerosols in that it allows a greater use of liquid components not miscible with the propellants. Water is not miscible with liquefied-gas propellants and, in many instances, presents a problem, since active ingredients are soluble in water. With the increased emphasis upon the decrease of volatile organic compounds (VOCs) in all products, these systems are finding increased use. These problems have been overcome to a large extent by use of the threephase system. Depending on the nature of the formulation, one of the following two systems may be employed. Dimethyl ether is most useful for products containing large amounts of water.
4. Two-layer system – In this system the liquid propellant, the vaporized propellant, and the aqueous solution of active ingredients make up the three phases. Since the liquid propellant and water are not miscible, the liquid propellant will separate as an immiscible layer. When a hydro alcohol mixture is used, the propellant and hydro alcohol solution will mix and form a single layer. When this propellant is of the fluorocarbon type, being denser than water, it will fall to the bottom of the container. Hydrocarbons, on the other hand, are lighter than water and, when used in this manner, will float on top of the aqueous layer. A spray is produced by the mechanical action of an exceedingly small valve orifice through which the liquid and some vaporized propellant are forced by the vapor pressure of the propellant. The vapor layer is replaced continuously by vaporization of the liquid layer of propellant. This action results in the maintenance of a constant vapor pressure in the headspace. An important characteristic of this system is that the propellant layer can be adjusted by varying the components so its specific gravity is almost equal to, but does not exceed, that of the hydroalcoholic phase. This system is designed to dispense pressurized products efficiently and economically, using relatively small amounts of hydrocarbon, HFA, or HCFC propellants.
5. Foam system – Foam aerosols, which often are classified separately, consist of three-phase systems in which the liquid propellant, which normally does not exceed 10 to 15 percent by weight, is emulsified with the drug-containing liquid. When the valve is depressed, the emulsion is forced through the nozzle, and in the presence of warm air and at atmospheric pressure, the entrapped propellant reverts to a vapor and whips the emulsion into a foam. The use of a dip tube is optional with this type of system, and when present, the container is designed for upright use. For those containers where the dip tube is omitted, the container must be inverted prior to use.
6. Compressed-gas aerosols – Aerosols using compressed gases as the propellant are finding increased use. These propellants, especially nitrogen, carbon dioxide, and nitrous oxide, are acceptable for use with pharmaceuticals. Compressed gases are used to dispense the product as a solid stream, wet spray, or foam. These aerosol products use an inert gas such as nitrogen, carbon dioxide, or nitrous oxide as the propellant. The gas is compressed in the container, and it is the expansion of the compressed gas that provides the push or the force necessary to expel the contents from the container. As the contents of the container are expelled, the volume of the gas will increase, causing a drop in pressure, according to Boyle’s law. This enables one to calculate the drop in pressure as the contents of a compressed-gas aerosol are used. Depending upon the nature of the formulation and the type of compressed gas used, the product may be dispensed as a semisolid, foam, or spray.
7. Semisolid dispensing – The concentrate generally is semisolid in nature, and since the gas is insoluble and immiscible with the concentrate, the product is dispensed in its original form. This system is applicable to the dispensing of dental creams, hair dressings, ointments, creams, cosmetic creams, foods, and other products. Compressed-gas aerosols operate at a substantially higher initial pressure of 90 to 100 psig at 70°F (21°C). This pressure is necessary to ensure adequate pressure for the dispensing of most of the contents from the container. The amount of product retained in the unit after exhaustion of the pressure varies with the viscosity of the product and loss of pressure, due to seepage of gas during storage. Since the concentrate generally is semisolid in nature and the dispensing characteristics depend largely on the viscosity of the product and the pressure within the container, the viscosity of the product concentrate must be adjusted accordingly.
8. Foam dispensing – Soluble compressed gases, such as nitrous oxide and carbon dioxide, can be used to produce a foam when used with emulsion products. This system is typical for whipped creams and toppings and several pharmaceutical and veterinary products. When this system is used, the gas dissolved in the concentrate will be evolved and cause a whipping of the emulsion into a foam. To facilitate the formation of a foam, this system is shaken prior to use to disperse some of the gas throughout the product concentrate.
9. Spray dispensing – This system is similar to a space or surface spray except that a compressed gas is used as the propellant. Since these gases do not possess the dispersing power of the liquefied gases, a mechanical breakup actuator is used. The product is dispensed as a wet spray and is applicable to solutions of medicinal agents in aqueous solvents. Another application for this type of system is found in the contact lens saline solutions. These consist of a normal saline solution packaged in an aluminum aerosol container and pressurized with nitrogen. Since these solutions may come in contact with the eye, they are sterilized using cobalt-60 gamma irradiation.
10.Barrier-type systems – The barrier-type aerosol system is gaining popularity in the pharmaceutical prescription and over-the-counter markets. Currently many of the sunscreen products are formulated in a barrier system into a spray, lotion or foam. These packaging systems are desirable because they are compact, portable, and ease to rub in. These systems separate the propellant from the product itself. The pressure on the outside of the barrier serves to push the contents from the container.
11. Piston type – Since it is difficult to empty the contents of a semisolid from an aerosol container completely, a piston-type aerosol system has been developed. This uses a polyethylene piston fitted into an aluminum container. The product is placed into the upper portion of the container. The pressure from nitrogen (about 90 to 100 psig) or a liquefied gas pushes against the other side of the piston, and when the valve is opened, the product is dispensed. The piston scrapes against the sides of the container and dispenses most of the product concentrate. This system has been used successfully to package cheese spreads, cake decorating icings, and some ointments and creams. Since the products that use this system are semisolid and viscous, they are dispensed as a lazy stream rather than as a foam or spray. This system is limited to viscous materials since limpid liquids, such as water or alcohol, will pass between the wall of the container and the piston. The piston type system has also been used to formulate post-foaming type gels.
12. Plastic-bag and bag-in-bag type – This system consists of a collapsible plastic bag fitted into a standard, three-piece tinplate or aluminum container. The product is placed within the bag, and the propellant is added through the bottom of the container. Since the product is placed into a plastic bag, there is no contact between the product and the container wall except for any product that may escape by permeation through the plastic bag. The valve and a collapsed inner bag are inserted into a container. A compressed or liquefied gas is added at the same time as the valve/bag is inserted, and then the valve is crimped. The product is forced through the valve and into the bag. The bag expands and will compress the propellant resulting in an increase in pressure. As the valve is opened, the product will be dispensed. Ointments, creams, and gels can be packaged in this system.
13. Can-in-can system – It is a system consisting of an aluminum can into which a second aluminum thin-walled can has been inserted. This inner can is glued to the outer can at the neck and forms a gas-tight seal. Then the neck of the can is fabricated. The propellant (liquid or compressed) is added through a small opening in the bottom of the can that is sealed with a rubber plug. A recent addition to this system includes replacement of the inner aluminum pouch with an inner plastic bag made of organic polymers. Sufficient space remains between this bag and the walls and the bottom of the outer container to accommodate sufficient propellant to evacuate the product completely.
Multiple choice questions:
1.Inhalation therapy also has been applied to delivery of drugs through
a)nasal mucosa
b)oral cavity
c)both of these
d)none of these
2.Drugs administered via the respiratory system (inhalation therapy) can be delivered through
a)dry powder inhaler
b)nasal inhaler
c)metered-dose aerosol inhaler
d)all of these
3.Advantages of aerosols are
a)Rapid onset of action
b)Container and valve closure are tamperproof
c)Dose titration to individual needs and ideal for prn medication
d)All of these
4.Which of the following statement defines an aerosol exactly?
a)The term aerosol is used to denote various systems ranging from those of a colloidal nature to systems consisting of pressurized packages
b)Aerosols have been defined as colloidal systems consisting of very finely subdivided liquid or solid particles, dispersed in and surrounded by a gas
c)Aerosol refers to those products that depend upon the power of a liquefied or compressed gas to dispense the active ingredient(s) in a finely dispersed spray, foam, or semisolid
d)All of these
5.Pump systems that also dispense the active ingredient(s) in the form of a finely dispersed mist (although of greater particle size) often are classified as aerosols.
a)true
b)false
6.Mode of operation of aerosols is/are
a)Two-phase system
b)Two-layer system
c)Barrier-type systems
d)All of these
7.The compounds chosen for Liquefied-gas systems generally have boiling points
a)below 70°F
b)below 21°C
c)above 70°F
d)a and b
8.When a liquefied-gas propellant is placed into a sealed container, it immediately gets miscible.
a)true
b)false
9.Which of the following consists of a solution or a suspension of active ingredients in liquid propellant or a mixture of liquid propellant and solvent?
a)Two-phase system
b)Two-layer system
c)Barrier-type systems
d)Foam system
10.Two-phase system is used to formulate aerosols for
a)inhalation
b)nasal application
c)topical application
d)a and b
11.Three-phase system is useful for
a)inhalation
b)nasal application
c)topical application
d)all of these
12.Which of the following system is designed to dispense pressurized products efficiently and economically, using relatively small amounts of hydrocarbon, HFA, or HCFC propellants?
a)Two-phase system
b)Two-layer system
c)Barrier-type systems
d)Foam system
13.Compressed gases are used to dispense the product as
a)solid stream
b)wet spray
c)foam
d)all of these
14.Semisolid dispensing is applicable to the dispensing of
a)dental creams
b)hair dressings
c)ointments
d)all of these
15.This system consists of a collapsible plastic bag fitted into a standard, three-piece tinplate or aluminum container. Identify
a)Plastic-bag and bag-in-bag type
b)Can-in-can system
c)both of these
d)none of these
Solutions:
- c)both of these
- d)all of these
- d)All of these
- d)All of these
- a)true
- d)All of these
- d)a and b
- b)false
- a)Two-phase system
- d)a and b
- c)topical application
- b)Two-layer system
- d)all of these
- d)all of these
- a)Plastic-bag and bag-in-bag type
References:
- Remington Essential of Pharmaceutics, 1st edition 2013, page no. 633-638.
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