Liquid Dosage Forms - Disperse Systems: Aerosols

Question 1

What are pharmaceutical aerosols

Answer 1

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

Question 2

Aerosols can be classified as

Answer 2

• 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

Question 3

Aerosols are used for local/systemic delivery of drugs as:

Answer 3

• 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

Question 4

Advantages of aerosols

Answer 4

• 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

Question 5

Disadvantages of aerosols

Answer 5

• Expensive
• Performance can deteriorate during life of product
• limited safety hazard (flammable, pressurized)

Question 6

Components of aerosols

Answer 6

• Product concentrate (dispersed phase) - can be liquid, emulsion, suspension, solid or powder; contains API
• Propellant (continuous phase): liquefied gas, compressed gas

Question 7

Functions of propellant

Answer 7

• Provide the driving force to expel product from its container
• Provide the dispersion medium -> act as a solvent/vehicle

Question 8

Describe liquefied gas propellant

Answer 8

• 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

Question 9

Examples of liquefied gas propellant

Answer 9

• Fluorinated hydrocarbon
• Hydrocarbon
• Chlorofluorocarbons
• Hydrofluoroalkanes

Question 10

Describe compressed gas propellant

Answer 10

• 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

Question 11

Examples of compressed gas propellant

Answer 11

CO2, N2 (inert gases)

Question 12

Advantages of compressed gas propellant

Answer 12

• Low inhalation toxicity
• High purity and chemical stability
• Inexpensive
• No environmental problems

Question 13

Disadvantages of compressed gas propellant

Answer 13

• Require use of a nonvolatile co-solvent
• Produce coarse droplet sprays
• Pressure decreases upon use

Question 14

Advantages of N2 as a propellant

Answer 14

• Insoluble in the product concentrate, inert

- Odorless and tasteless

Question 15

Mixture of propellants allow variation in

Answer 15

• Vapor pressure - droplet size, leakage, choice filling process
• Liquid density - irreproducible unit doses
• Solvency - insoluble, partially soluble, completely soluble

Question 16

Advantages of hydrocarbon propellants

Answer 16

• Inexpensive
• Excellent solvents
• Minimal ozone depletion
• Negligible “greenhouse effect”

Question 17

Disadvantages of hydrocarbon propellants

Answer 17

• Flammable
• Low liquid density
• Unknown toxicity following inhalation

Question 18

Advantages of chlorofluorocarbons propellants

Answer 18

• Low inhalation toxicity
• High chemical stability
• High purity
• CFC-11 is a good solvent

Question 19

Disadvantages of chlorofluorocarbons propellants

Answer 19

• High cost
• Destructive to atmospheric ozone
• Contribute to the “greenhouse effect”

Question 20

Advantages of hydrofluoroalkanes propellants

Answer 20

• Low inhalation toxicity
• High chemical stability
• High purity
• Not ozone depleting

Question 21

Disadvantages of hydrofluoroalkanes propellants

Answer 21

• Poor solvents
• Minor “greenhouse effect”
• High cost

Question 22

What is a metered dose inhalers

Answer 22

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

Question 23

What is an actuator

Answer 23

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

Question 24

Describe the aerosol principle

Answer 24

• 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

Question 25

Pressure of an aerosol can be controlled by

Answer 25

- Nature and amount of the product concentrate | - Type and amount of propellant - space sprays (85%), surface sprays (30-70%) and aerated sprays (6-10%)

Question 26

What are the aerosol systems

Answer 26

1. 2-phase system: liquid phase (product concentrate + liquefied propellant) and vapour phase 2. 3-phase system: water immiscible liquid propellant, highly aqueous product concentrate, vapor phase (replenished from the liquid propellant phase) 3. 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

Question 27

What are the 2 filling operations

Answer 27

- 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

Question 28

Disadvantages of cold filling

Answer 28

- Aqueous systems cannot be filled - water turns to ice at this low temp. - Moisture may also appear

Question 29

Advantages of pressure filling

Answer 29

- Minimize danger of moisture contamination | - Less propellant lost

Question 30

What are the tests for filled containers

Answer 30

- 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

Question 31

What are the problems encountered for filled containers

Answer 31

- Underfill due to propellant escape - Distorted/incorrect filling nozzle - Low propellant injection pressure - Distortion of the ferrule top due to poor crimping

Question 32

What are the warning labels for the containers

Answer 32

- 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