Aerosols:
What are pharmaceutical aerosols?
- Packing of dosage forms containing one or more active ingredients which upon
actuation emit a fine mist or dispersion of a liquid or solid materials in a gaseous
medium
- Formulation in a propellant (gas, mixture of gases or liquefied gases)
- Similar to other disperse systems (emulsions and suspensions) in that they are
designed to deliver drug either topically or systemically e.g.: metered dose of
salbutamol, deep freeze spray, sunscreen, mosquito repellant, Nicorette spray (mist,
than spray)
What is the difference between a mist and an aerosol?
- Mist doesn’t contain propellant
- More of a water based formulation
- Aerosole higher speed - from liquified to gaseous
- Mist - slower speed
What are the advantages of aerosols?
- A dose can be removed without contamination of the content of the formulation
- Stability is enhanced for these substances adversely affected by oxygen and/or
moisture
- The medication can be delivered directly to the affected area in a desired form.
Such as spray, steam, quick breaking foam, or stable foam
- Irritation produced by the mechanical application of topical medication is reduced or
eliminated
- Easy to use --> Increased patient compliance
1. A portion of medication may be easily withdrawn from the container w/o
contamination or exposure to the remaining material
2. Topical medication may be applied in a uniform thin layer to the skin w/o touching
the affected area this reduce the irritation resulted from the mechanical (fingertip)
application of the topical preparation
3. Aerosol application is a clean process, requiring little or no wash up by the user
4. The aerosol container protects drug molecules that are adversely
5. affected by atmospheric oxygen and water (dispersed in non aqueous medium)
and light.
6. The valve control the physical form and the particle size of the emitted product,
therefore, it can reach into lower respiratory tracts for local treating lung diseases and
minimizing systemic side effects
What are the disadvantages?
- Environmental hazards associated w/ the use of some propellants
- Potential allergic reactions to propellants or other pharmaceutical ingredients
Why are patients asked to shake aerosols?
- Aerosol - suspension, not solution, why patients are asked to shake well
What are the Application of aerosols?
- Drug powder or solution that are administered by the respiratory route, for their local
actions on the bronchial tree or for their systemic effects through absorption from the
lungs
- Upon actuation they give a specified dose (MDIs)
- Rapid onset of action compared with systemic route due to large surface area of
lung mucosa
- Mainly used for local treatments but also explored for systemic delivery.
- Ex. Powder drugs: tiotropium bromide in COPD.
- Ex. Suspension: Ventolin® (Salbutamol sulphate).
Content of aerosols
What are the contents of the aerosols?
- The contents of aerosol are mainly made up of 2 components
1. Active ingredient - in form of a liquid, emulsion, or suspension
2. The propellant - can be liquefied gas, or even a compressed gas
The propellant is the driving force (engine) behind the aerosol
What systems can aerosols exist as?
Aerosols may be:
1-Two phase system
1.Liquid phase containing liquified propellant and product concentrate
2.Vapour phase
2. Three phase system
1. Water immiscible liquid propellant
2. Highly aqueous layer (product concentrate)
3. The vapor phase
The aerosol principle:
What are the 3 components of an aerosol?
1. The active ingredient and excipients such as antioxidant, surfactant and/or diluent
2. The propellant- Compressed gasses/liquefied gases, such as CFCs
3. Containers
Attributes:
Why is a propellent an important element?
- Propellant is an important element, to force the drug out of the container through
the valve assembly → metered or non-metered dose
- Aerosol products may designed to expel their products as a: fine mist, a coarse, wet
or a dry spray or as a foam
METERING valve
1. Reproducible delivery of 25-100 microliters - small volume of
liquified
propellant
2. Depression of valve stem activated discharge through opening
3. After release, metering chamber re-fils from canister
- Valve is important as if you are considering deodorant or
sunscreen, or whatever can be used in large amounts w/o
concerns for overdose → cannisters that spray cont
- But when delivering drugs, which must be delivered in certain
doses → want control about how much drug is coming out of
device → metering valve works well, really important in MDI
(metered
dose inhaler)
Liquefied propellants
- 2 phase system - liquid and head of vapor
What is liquefied propellant?
- Gases that exist as liquids under pressure
- Because the aerosol is under pressure the propellants exists mainly
as a liquid but it will also be in the head space as a gas
- as the valve is opened pressure is released and some of the liquid
propellant turns to gas and keeps the head space full of gas.
- every time actuated, liquid goes down + vapour space increases →
vapour pressure stays constant
- In this way the pressure in the can remains essentially constant and
the spray performance is maintained throughout the life of the aerosol.
Compressed gas propellants
How do Compressed gas propellants work?
- Propellants also occupy the headspace above the liquid in the can
- When aerosol valve is opened, the gas ‘pushes’ the liquid out of the
can
- The amount of gas in the headspace remains the same but it has more
space, and as a result the pressure will drop during the life of the can.
- Spray performance is maintained however by careful choice of the
aerosol valve and actuator.
What are the Typical propellants?
1. Liquefied petroleum gas (LPG): consists of high purity hydrocarbons derived
directly from oil wells, and as a by product from the petroleum industry. Mixture of
propane, iso-butane, and n-butane. They are used in most aerosols today and have
been used for many years in household aerosol products. They are flammable.
2. Dimethyl Ether: alternative liquefied propellant. It is more common
3. in personal care products, and some air fresheners.
4. Chlorofluorocarbons (CFCs)
5. Hydrofluoroalkanes (HFAs)
6. non-soluble compressed gasses: e.g., compressed air and nitrogen. These are
sometimes seen in consumer products and are an environmental alternative to LPG.
7. Soluble compressed gasses: e.g. Carbon dioxide. This is another alternative to
LPG, but has limited use, mainly with alcoholic systems, such as air treatment
products, deodorants and personal care products.
What are the Physicochemical properties of propellants?
1. Vapour pressure
- inhalers, not a single gas being used as single gases never have the correct vapor
pressure
- total pressure in a system is equal to the sum of individual or partial pressures.
- Remember Raoult’s law: lowering of the vapor pressure of a liquid due to the
addition of another substance
- The dispersion of the vapor pressure of solvent upon the addition of solute is
proportional to the mole fraction of solute molecules in solution.
2. Boiling point
- it is essential in order to estimate the level of pressure that the formulation can be
exposed to and in orderto predict storage conditions
3. Liquid density and viscosity - the viscosity of liquid gases are extremely low
- Canister do not explode
Manufacturing - what are the 2 filling operations of cannisters?
1. Cold filling
2. Pressure filling
What is Cold filling?
- Entire formulation made into suspension in a cold vessel (-40oC) to prevent
propellant evaporation
- Cans are filled with mixture, then the valve is crimped on.
What is Pressure filling?
- Drug, surfactant and other excipients weighed into can.
- Valve is crimped onto can
- Propellant is filled through valve
Containers-What are the selections of choosing containers?
- Various materials have been used in the manufacture of aerosol containers include
glass, Metal
- (tin-plated steel, aluminum and stainless steel), Plastics
- The selection of container based on its adaptability to production
- methods, compatibility with formulation components, ability to sustain
- the pressure intended for the product, and the cost.
Why are glass containers preferred for most aerosols?
- Glass has high chemical compatibility with the formula compared to the metal
containers and is not subject
to corrosion
- Glass is also more adaptive to creativity in designed
Which containers are the most widely used and why?
- Tin-plated steel containers are the most widely used metal containers for aerosols.
- can accommodate high pressure with much less incompatibility than plastic
containers and they are non-breakable compared with glass
What are the problems with plastic containers?
- Health hazard due to leaching of some components (plasticizers) into the bulk
dispersion
- Problem w/ glass - light can pass through → degradation by photolysis --> use
amber bottle → stop uv light passing through
- Potential drug-plastic interactions, which can reduce the efficacy of the product
- Adsorption of the active ingredients onto the wall of the plastic container.
What are the Tests for aerosols?
1. Corrosion test
2. Hydrolysis test
3. Spray test
4. Solubility test
5. Leakage test
6. Durability test
7. Irritation test
8. Flame test
