-
Pulmonary Drug Delivery Systems is what?
Any procedure or device which allows a drug to be administered into the respiratory tract
-
What are inhalations?
Drug or Drug solutions administered nasally for local or systemic effects
-
What is an example of an inhalation given in class?
Stadol NS (Butorphenol tartate, an opiod pain medication)
-
What are aerosols?
Pressurized product that releases the active ingredient when the valve system is activated
-
What are examples of aerosols?
Ventoilin/Proventil (Albuterol sulfate, Bronchospasms)
-
What are the advantages of Pulmonary drug delivery systems?
- Mechanical irritation of topical applications is reduced
- May replace injection
- Maintains stability- protected from 02, moisture, light and unsterile conditions
- Facilitates self-administration
- Delivers drugs to the appropriate location in the correct form
- Faster action than oral
- Larger absorption area
- Avoids GI destruction
-
What does hermetic mean?
Sealed airtight
-
What are the disadvantages of Pulmonary delivery systems?
- Volatility of propellants may cause irritating cooling effect
- Fluorinated hydrocarbons may exhibit cardiotoxic effects when used repeatedly or rapidly
-
What are aerosols?
Suspensions of fine solids or liquids in air or gas
-
What factor controls aerosol ejection?
The power/pressure of the liquefied or pressurized gas
-
When did aerosols come into use?
1950s
-
What is the most common type of pulmonary drug delivery system?
Aerosols
-
What does the future of aerosol development depend on?
Development of new propellants
-
Explain how a two phase aerosol system works:
- Gasket seals access to the nozzle off
- When the nozzle is pressed, it penetrates the gasket and, creating a passage out of the container
-
What three physical properties of aerosol contents allows for ejection of the drug product?
- Equilibrium between liquefied and aerosolized drug product
- Vapor exerts pressure on the container and liquid form of product
- Actuation of the valve, allows pressure relief, expelling the contents
-
What happens to the drug after it is ejected from the aerosol?
It evaporates immediately
-
What happens in the aerosol container as the product is being released?
The equilibrium of the aerosolized and liquid product reestablishes
-
How does an aerosol product maintain even pressure and release rate?
By maintaining the equilibrium between aerosolized and liquefied product within the container
-
Under what condition will pressure and propulsion drop dramatically in an aerosol?
When the liquid reservoir is depleted
-
What are the four main components of an aerosol delivery system?
- Propellant
- Containers
- Product concentrate
- Valve assembly
-
What is the product concentrate?
The active ingredient mixed with required adjuncts
-
What are examples of the required adjuncts of the product concentrate?
- Solvents
- Surface active agents
- Antioxidants
-
What is the "Heart of the aerosol"?
The propellant
-
What is the purpose of the propellant?
To develop the proper pressure to the expel contents when the valve is open
-
What determines if an aerosol is a spray or a foam?
The Propellant
-
What type of propellant cannot be used as a solvent for the active ingredient?
Compressed gas propellants
-
What are the two classes of propellants?
- Liquefied gas propellants (includes fluorinated hydrocarbons and hydrocarbons)
- Compressed gas propellants
-
What are the two types of Liquid gas propellants?
- Fluorinated hydrocarbons
- Hydrocarbons
-
What three examples of Compressed gas propellants were given in class?
Carbon Dioxide, Nitrous oxide and Nitrogen
-
What type of propellants are Nitrous oxide, Carbon dioxide and Nitrogen?
Compressed gas propellants
-
What are three examples of Fluorinated hydrocarbon propellants given in class?
- Trichloromonofluoromethane (Propellant 11)
- Dichlorodifluoromethane (Propellant 12)
- Dichlorotetraflouromethane (Propellent 114)
-
What is Propellent 114?
- Dichlorotetrafluoromethane
- Liquid gas propellant
-
What is Propellant 12?
- Dichlorodifluoromethane
- Liquid Gas propellant
-
What is propellant 11?
- Trichloromonofluoromethane
- Liquid Gas propellant
-
What type of Propellant is used in aerosols for oral and inhalation uses?
Fluorinated hydrocarbon liquid gasses
-
What type of propellant would you use for topical purposes?
Hydrocarbon Liquid gasses
-
What three examples were given in class for hydrocarbon liquid gas propellants?
-
What category of propellants are Propellant 11, 12 and 114?
Fluorinated hydrocarbon liquid gasses
-
What category of propellants are isobutane, butane and propane?
Hydrocarbon liquid gasses
-
What category of propellants are carbon dioxide, Nitrogen and Nitrous oxide?
Compressed gas propellants
-
What are the five general characteristics of fluorinated hydrocarbon propellants?
- Deplete the ozone
- Chemically inert
- Non-toxic
- Flammable
- Expensive
-
What six general characteristics were given in class for Hydrocarbon propellants?
- Chemically stable
- Inflammable
- Inexpensive
- No hydrolysis
- Environmentally safe
- Low order of toxicity
-
What are four general characteristics of Compressed gas propellants?
- Produces a less stable foam than liquid gas propellants
- No cooling effect
- Low expansion power
- Used for food and non-food products that need to be dispensed in the original form
-
What example products were given that are make use of compressed air propellants?
- Dental creams
- Hair products
- Ointments
- Germicidal aerosols
- Antiseptics
-
What equations would you use to determine the vapor pressure of a mixture of propellants?
-
Summarize Dalton's law:
The total pressure of the system = The sum of all the partial pressures
-
Summarize Raoult's law:
 - The depression of the vapor pressure of a solvent with the addition of a solute = The mole fraction of the solute molecules in solution
-
What are examples of mixtures that create a negative deviation from Raoult's law?
- Chloroform and acetone
- Water and ethanol
-
What is an example of a mixture that strictly follows Raoult' law?
Ethylene chloride and Benzene
-
What characteristics must an aerosol container have?
- Able to withstand pressures of 140-180 psi
- Must be able to reach 103 degrees F
-
What are the three types of aerosol containers?
- Metal
- Synthetic resins or Plastics
- Glass
-
What types of glass are suitable for aerosols?
Uncoated or coated
-
What type of Metals are suitable for aerosols?
- Tin plated
- Stainless steel
- Aluminum
-
What are the five considerations in aerosol container selection?
- Aesthetics/Design
- Adaptability to production methods
- Ability to withstand pressure and heat
- Compatibility with product
- Cost
-
What is the function of the Valve assembly of an aerosol?
- Enables the product to be expelled
- In a desired form
- At a desired rate
- In the proper amount
-
What three components related to expelling the drug do valves regulate?
- The rate of delivery
- The amount delivered
- The Form delivered
-
What is the actuator of the valve assembly?
The button that the consumer uses to open the valve
-
What is the purpose of the valve assembly dip tube?
Brings formulation form the container to the valve
-
What is the purpose of the valve assembly Spring?
- The component that closes the valve after the actuator is released
- Prevents leakage when the valve is closed
-
What is the purpose of the valve assembly Housing?
Links the stem of the actuator and the dip tube
-
What is the purpose of the valve assembly Stem?
The mechanical piece that retracts when the actuator is released, closing the valve
-
What is the mounting cusp?
The area around the valve that holds it in place
-
What is the purpose of the gasket in a valve assembly?
To prevent leakage when the valve is closed
-
What are the requirements for aerosol valves?
- Must dispense the correct amount
- Must dispense the correct form
- Must be easily opened and closed
-
What are the two classifications of Aerosol valves?
Metered and non-metered
-
What is a metered valve?
One that dispenses a certain amount
-
What are the types of actuators?
- Spray
- Foam
- Solid Stream
- Specialty for eye nose and throat delivery
-
What two things does the actuator aid in?
- Easy opening and closing
- They type of product discharged
-
What are the aerosol formulation parts?
- The product concentrate
- The propellant
-
How many propellants can be used in an aerosol?
One or more
-
What are the four type of aerosol formulation systems?
- Water based
- Solutions
- Suspension-dispersion
- Foam systems
-
What are the two processes for aerosol production?
- Cold process
- Pressure Process
-
Summarize the cold process of aerosol production:
- The propellant, product concentrate and container are cooled to -30 or -40 degrees F
- The propellant and concentrate are placed into the container
- Liquid gas is overlayed in the container
- The valve assembly is added and crimped into place
-
How is air expelled from the container in the cold process of aerosol assembly?
The liquid gas overlay is heavier and pushes the air out during assembly
-
Summarize the pressure process of aerosol manufacturing:
- The product concentrate is added t the container
- The valve is crimped into place
- The air is removed by vacuum
- The propellant is added through the valve assembly utilizing the vapor pressure force
-
How is air removed from the container in the pressure process of aerosol manufacturing?
By vacuum after the valve has been crimped into place
-
What process is used for most aerosol manufacturing?
The pressure process
-
What are the advantages of The pressure process of aerosol manufacturing?
- Less risk of moisture contamination
- Less propellant loss during manufacturing
-
What type of propellants were used before 1978?
Fluorinated Hydrocarbons
-
What type of fluorinated Hydrocarbons were not banned in the 1970s?
Those for inhalation/nasal or oral use
-
What are the alternatives to fluorinated hydrocarbon propellants?
- Compressed gasses
- Hydrocarbons
- Mechanical pumps
-
What are the two most common types of containers used for aerosols?
Glass and Metal
-
What should be carefully considered prior to packaging in aluminum?
Alcohol (due to chemical reactivity)
-
What type of aerosol products should be used in glass?
- No more than 15% propellant
- no more than 25 psi
-
What type of aerosol products need special attention when choosing a container?
Acids and soaps
-
What factors contribute to the selection of Valves and actuators?
- The size of the orifice
- The application
- Material used to construct it
-
What factors contribute to the selection of aerosol applicators?
The type of application (nasal, inhalation, etc)
-
What 8 characteristics are used as indicators of stability for the aerosol product concentrate?
- pH
- Density
- Viscosity
- Vapor pressure
- Assay of ingredients
- Odor
- Color
- Total weight
-
What is the aerosol container examined for in terms of stability?
Corrosion during storage
-
What stability measures are performed on aerosol valve assemblies?
Function of the valve over time (satisfactory product dispensing, opening an d closing correctly, etc...)
-
What two ways are aerosols tested for Flammability/Combustibility?
- Flash test
- Flame Projection
-
What is the Flash point test for Aerosols?
- The aerosol product is cooled to -25 degrees F
- The product is placed in a ignition chamber
- The temperature is raised until it ignites
-
What is the Flash point (the point not the test)?
The temperature at which an aerosol ignites
-
Describe the Flame projection test for aerosols:
- The product is sprayed for four seconds into a flame
- The extension of the flame is measured by a ruler
-
What would you measure using a pycnometer or hydrometer?
The density
-
What methods can be used to determine the moisture content of an aerosol?
- Gas chromatography
- Karl Fischer method
-
What can be used to identify product contents of an aerosol?
-
What would you use and artificial respiratory system for?
To determine the amount of drug received by the patient
-
How is the reproducibility of metered doses determined for an aerosol?
By analysis of drug components
-
What would you use to evaluate foam stability?
- Visual = time it takes to penetrate the foam
- Rotational viscometer
-
What methods are used to determine the particle size of an aerosol product?
- Light scatter decay method
- Cascade impactor
-
How does the Cascade impactor work?
- Gas is projected through a series of nozzles and glass slides
- Larger particles become impacted in earlier slides at lower velocities
-
What two areas are considered when testing the Biological efficiency of aerosol products?
- Therapeutic activity
- Toxicity
|
|
