Liquid Dosage Forms - Disperse Systems: Aerosols Flashcards
What are pharmaceutical aerosols
Pressurized dosage forms that upon actuation emit a fine dispersion of liquid and/or solid materials containing one or more active ingredients in a gaseous medium
Aerosols can be classified as
- Space sprays - disperse ingredients as an airborne mist with particle size <50um in diameter (e.g. room deodorizer, disinfectants)
- Surface sprays - disperse larger particle, generally produce a wet/coarse spray on a surface (e.g. perfumes, hair spray)
- Aerated sprays - disperse medicated foams, vaginal foams, shaving cream
Aerosols are used for local/systemic delivery of drugs as:
- Oral and lingual - antacids, local anesthetics, antiseptics
- Nasal - decongestants, anti-inflammatory steroids
- Ocular - contact lens cleaning
- Respiratory - bronchodilators, anti-inflammatory steroids, antiallergies, antivirals, smoking cessation
- Rectal - local anesthetics, anti-inflammatory steroids
- Vaginal - contraceptive foams e.g. Nonoxyenol-9
Advantages of aerosols
- Portable, easy to use and convenient
- Max stability
- Min concentration
- Can be filled aseptically
- reduce irritation; cooling effect
- easy to control
- protect unstable drugs from light, oxygen and moisture
Disadvantages of aerosols
- Expensive
- Performance can deteriorate during life of product
- limited safety hazard (flammable, pressurized)
Components of aerosols
- Product concentrate (dispersed phase) - can be liquid, emulsion, suspension, solid or powder; contains API
- Propellant (continuous phase): liquefied gas, compressed gas
Functions of propellant
- Provide the driving force to expel product from its container
- Provide the dispersion medium -> act as a solvent/vehicle
Describe liquefied gas propellant
- Gases that exist as liquids under pressure
- Propellant exists mainly as a liquid but it will also be in the head space as a gas
- When the product is used up, some of the liquid propellant will turn into gas to maintain the pressure in the can so that the spray performance is maintained
Examples of liquefied gas propellant
- Fluorinated hydrocarbon
- Hydrocarbon
- Chlorofluorocarbons
- Hydrofluoroalkanes
Describe compressed gas propellant
- Only occupy the head space above the liquid in the can
- When the valve opens, the gas pushes liquid out of the can, amount of gas remains constant but the pressure drops (more space in can)
- Spray performance is maintained by careful choice of the aerosol valve and actuator
Examples of compressed gas propellant
CO2, N2 (inert gases)
Advantages of compressed gas propellant
- Low inhalation toxicity
- High purity and chemical stability
- Inexpensive
- No environmental problems
Disadvantages of compressed gas propellant
- Require use of a nonvolatile co-solvent
- Produce coarse droplet sprays
- Pressure decreases upon use
Advantages of N2 as a propellant
- Insoluble in the product concentrate, inert
- Odorless and tasteless
Mixture of propellants allow variation in
- Vapor pressure - droplet size, leakage, choice filling process
- Liquid density - irreproducible unit doses
- Solvency - insoluble, partially soluble, completely soluble
Advantages of hydrocarbon propellants
- Inexpensive
- Excellent solvents
- Minimal ozone depletion
- Negligible “greenhouse effect”
Disadvantages of hydrocarbon propellants
- Flammable
- Low liquid density
- Unknown toxicity following inhalation
Advantages of chlorofluorocarbons propellants
- Low inhalation toxicity
- High chemical stability
- High purity
- CFC-11 is a good solvent
Disadvantages of chlorofluorocarbons propellants
- High cost
- Destructive to atmospheric ozone
- Contribute to the “greenhouse effect”
Advantages of hydrofluoroalkanes propellants
- Low inhalation toxicity
- High chemical stability
- High purity
- Not ozone depleting
Disadvantages of hydrofluoroalkanes propellants
- Poor solvents
- Minor “greenhouse effect”
- High cost
What is a metered dose inhalers
A device that contains drug in a liquid suspension/solution and uses a propellant to fire a measured dose of drug consistently over time; use for all inhalation and some topical aerosols
What is an actuator
A component which allows the patient to activate the metering valve on an MDI and deliver a precise dose of drug through mouth to the lungs
Describe the aerosol principle
- The valve and actuator contain small holes and channels to control the flow rate and characteristics of the spray which emerges from the actuator
- When the actuator is depressed, it pushes the valve stem down against the spring.
- The valve stem moves down through the inner gasket, and when the hole is below the level of the gasket, liquid flows up through the dip tube into the valve housing, then through the valve stem to the actuator
- Liquid continues to flow due to the internal propellant pressure until the valve is closed when the operator releases the pressure
Pressure of an aerosol can be controlled by
- Nature and amount of the product concentrate
- Type and amount of propellant - space sprays (85%), surface sprays (30-70%) and aerated sprays (6-10%)
What are the aerosol systems
- 2-phase system: liquid phase (product concentrate + liquefied propellant) and vapour phase
- 3-phase system: water immiscible liquid propellant, highly aqueous product concentrate, vapor phase (replenished from the liquid propellant phase)
- Compressed gas systems - pressure of the compressed gas contained in the headspace of the aerosol container forces the product concentrate up the dip tube and out of the valve, higher gas pressure is required
What are the 2 filling operations
- Cold filling - product concentrate and the propellant cooled to -34.5 to -40 to liquefy the propellant gas, container should be cooled
- Pressure filling - product concentrate is quantitatively placed in the container and the desired amount of the propellant is allowed to enter the container under its own vapor pressure, used for most pharmaceutical formulations
Disadvantages of cold filling
- Aqueous systems cannot be filled - water turns to ice at this low temp.
- Moisture may also appear
Advantages of pressure filling
- Minimize danger of moisture contamination
- Less propellant lost
What are the tests for filled containers
- Test for leaks or weaknesses
- Proper function of the valve and discharge rate
- Test for accuracy and reproducibility of dosage when using metered valve
- Test for particle size distribution
What are the problems encountered for filled containers
- Underfill due to propellant escape
- Distorted/incorrect filling nozzle
- Low propellant injection pressure
- Distortion of the ferrule top due to poor crimping
What are the warning labels for the containers
- Avoid inhaling
- Do not inhale directly. Deliberate inhalation of contents can cause death
- Keep away from eyes or other mucous membranes
- Contents under pressure. Do not puncture/incinerate container
- Do not expose to heat or store at temp above 49
