Aerosols Flashcards
what is an aerosol
An aerosol is a dispersion of solid or liquid particles (typically <50 micrometers diameter) in gas
How does an aerosol work?
- Pressing on the actuator allows the product to come out through the valve
- Contents are a combination of ingredients and propellant specifically formulated to form the products specific job
- Dip tube reaches down to the bottom of container to carry product to valve
Curved bottom allows dip tube to reach and use all the product
what are uses of respiratory therapy?
asthma, rhinitis, cystic fibrosis, COPD
What are 3 things to consider when developing a device?
API properties
Properties of the device
Site of action
what are API properties to consider
molecular weight
charge
solubility
lipophilicity
What are formulation properties to consider
disintegration
dissolution
particle size
wettability
what are some properties of the site of action (lungs)
have to overcome mucociliary clearance
have to go through the epithelial layer to deeper tissues where it acts
macrophages will clear foreign substances from the lungs
what are advantages of aerosols
Have localized effect: less side effect possibility (beta-2 agonists arent totally selective so can have some effect on the heart)
Faster than administering orally
Some of the devices actively propel the drug into the site of action
Dose administered is less than if the drug was delivered orally
Single dose: no contamination
Sensitive materials are protected
Irritation minimized or eliminated
Alternate route of administration (fewer side effects)
Easy and convenient to use
what is propellant
To develop the proper pressure within the container
Expel the product
Aid in atomization or foam production
what are the types of propellants
Chloro-fluoro hydrocarbons
Non-ozone depleting fluorocarbons
Hydrocarbons
Compressed gasses
what are the characteristics of CFCs
use is highly restricted low vapor pressure: liquid at low temps, gaseous at room temp chemically inert non-toxic (may be cardiotoxic at high doses) non-flammable non-polar (immiscible with water) capable of dissolving many substances phased out because of ozone depletion
what are the characteristics of non-ozone depleting fluorocarbons (HFA)
Alternative to CFCs
Low to high pressure
Non-flammable
Non-ozone depleting
Chemically inert and toxicologically safe
Low vapor pressure–>liquid at low temps, gaseous at room temp
what are the characteristics of hydrocarbons
suitable replacement of CFCs
Immiscible with water
Flammability restricts their use
Used in foam and water-based aerosols only
Blend of fluorinated hydrocarbons and/or hydrocarbons can be used: by changing the proportions of propellants any desired vapor pressure can be achieved
Low vapor pressure–>liquid at low temps, gaseous at room temp
Examples: propane, butane, isobutane
How CFC, HFA and HC work
- Equilibrium between the liquefied propellant and vapor 2. Actuator is pressed: vapor pressure forces the liquid up the dip tube 3. Release through the orifice into the atmosphere 4. Liquid propellant evaporates (due to the drop in pressure: instantly (Always an equilibrium between the liquid and the gas phase of the propellant which means the pressure is always constant in the canister) 5. Product concentrate: airborne liquid droplets or dry particles which is then inhaled or deposited 6. New equilibrium is established between the remaining liquid propellant and its vapor (The pressure in the container remains constant during the use of the aerosol)
what are the characteristics of compressed gasses
Don’t liquefy at high pressure or low temperature: always remain a gas
Limited value for aqueous products
Applicable in topical preparations
Product use–>volume in the container decreases–>pressure in the container drops (due to reduction in compression): Drop in pressure may affect the dose dispensed
Examples: nitrogen, nitrous oxide, carbon dioxide
what are the components of aerosols
Propellants
Product concentrate
Container
valve and actuator
Different types of product concentrate systems
Solution systems (2 phase) Suspension systems Emulsion systems (3 phase)
what is a solution system
Solution of active ingredient in pure propellant
Equilibrium between the liquid propellant (and drug) and the propellant vapor
Alcohols: auxiliary solvent
what is a suspension system
Active ingredient dispersed in the propellants
Have temperature changes when actuating the device: can cause drugs to have decreased solubility in the propellant (if in solution) and can cause crystallization THEREFORE need a propellant the drug is completely insoluble in so that the drug doesn’t precipitate out of solution
what is the issue with solution and suspension systems
particle agglomeration
Causes: Valve clogging, Inaccuracy of dosing, Damage to the container
Surfactants and lubricants: reduce agglomeration and to lubricate the particles in their passage through the valve orifices (Non-ionic surfactants (HLB<10), mineral oil, isopropyl myristate)
what are ways to ensure physical stability of suspension and solution systems
Controlling moisture content (most propellants are hydrophobic and need to control drugs solubility)
Use of a drug derivative with a minimum solubility in the propellant
Particle size reduction (deposition of drug at site of action is controlled by particle size)
Using a dispersing agent (reduces sedimentation)
what are the 2 types of emulsion systems
Foam and spray emulsions
what is a foam system
Propellant in the internal phase (o/w emulsion)
7-10% propellant used
propellant escapes from droplets to form gas phase to maintain equilibrium
Quick-breaking foams: contain alcohol, water and surfactant (Propellant expands rapidly as it incorporates more gas which cause it to become a foam)
Stable foam: produced when surfactants are used that have limited solubility in both phases
what is a spray emulsion
Propellant in the external phase (w/o emulsion)
Contain 25-30% propellant
No foaming
Propellant is in equilibrium between gas phase and liquid phase
Amount of the propellant is not more than 50% but still w/o emulsion
what are the materials often used in containers for aerosols
Metal: most commonly used (aluminum reacts with CFCs)
Glass: preferred as it is inert compared to metal
what are the types of valves used?
continuous and metered
what is one important thing to consider when choosing materials for the valve and actuator
Need to ensure the ingredients are compatible with all the components (rubber, metal) to make sure it doesn’t corrode
how do continous valves work
Actuator is depressed–.pushes the valve stem down against the spring
Valve stem moves down through the inner gasket
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 will continue to flow due to the internal pressure exerted by the propellant
Valve is closed when the operator releases the pressure on the actuator, valve stem is pushed upwards by the spring
what are metered valves
Metering chamber determines the volume of the product
Minimizes administration errors
Delivery into the nasal passageway and respiratory tract is improved
Delivery: 10-15% of the dose actuated into the airways (10% lost to the inner surface of the adapter; 80% deposits in the oropharynx area (swallowed and systemically absorbed)
how do metered valves work
2 different chambers:
Small inner chamber with a defined volume
Have quite a number of openings
In resting: there is an opening between the canister and the metered dose chamber and the internal chamber fills up with drug product
Depress: opening between chamber and small inner chamber closes and the inner changes opens up to the air
When you let go: inner chamber opens up to the big chamber: takes 10-15 seconds to refill the inner chamber
what do spacers do
Spacers may enhance the delivery of the medicine and make it easier to coordinate the spray with breathing
Spacers may trap large particles of the spray so they don’t land on the inside of the mouth where they might cause infections
what is a DPI?
Devices are pre-loaded with pure drug within the device
Actuation: twisting the bottom of the device
Operation of inhaler based on patient inspiration
advantages of DPIs
Patients with difficulty coordinating activation of the MDI with inspiration
Not affected by cold air
Some devices may be checked to see if the full dose has been inhaled Patient may inhale repeatedly until the full dose is received
No propellant so easier to formulate
Disadvantages of DPIs
Variable inspiratory flow rate causes a large dose variability
Loss of dry powders in the capsule, inhaler, and oropharynx is quite high–>requires a higher dose
Come patients don’t like the gritty sensation/taste
Some powders may be irritating (lactose fillers)
Less effective in acute situations
Powder may be lost when device is tipped
Requires adequate inspiratory drive
Few drugs available as DPIs
Patients may repeat doses unnecessarily because there is no sensation of powder/propellant entering the lungs
Special things to know about turbuhalers
As the patient inhales the drug passes through a spiral channel and is de-aggregated Patients may not taste, smell, or feel the delivered particles
Has a drying agent in it: not the medication you hear when you shake it just the drying agent
Medication is compressed so it doesn’t make a sound
what is a nebulizer
Use a compressor to aerosolize liquid medication
Effective delivery method for infants and young children
Small plastic devices which contain the drug solution are drive n by a flow of gas of 6-8L/min
what is an advantage of nebulizer therapy
less dependent on patient coordination or cooperation
who needs nebulizer therapy
Emergency treatment for acute asthma and COPD
Long-term bronchodilator treatment of chronic airflow obstruction
Prophylactic drug treatment for asthma
Antibiotics for cystic fibrosis, bronchiectasis, and HIV/AIDs
Symptom relief in palliative care
How does a compressed air/oxygen (jet nebulizer)
pressurized jet air stream enters through a narrow tube and is forced through a narrow opening called the venturi
The jet stream causes a pressure drop near the venturi
decreased pressure causes liquid drug in the reservoir to be sucked up through the liquid feeding tube
jet stream strikes the rising liquid and breaks it up into droplets of various sizes
small droplets are pushed by the jet stream out of the nebulizer as a fine mist that is inhaled by the patient
how does a ultrasonic nebulizer work
produce droplets using high-frequency sound waves
droplet size is determined by the frequency of the sound waves
advantages of nebulizers
May be used with young children and those who are unable to receive adequate dosage from other devices Good lung penetration is usually achieved
It is possible to mix 2 medications into one treatment
disadvantages of nebulizers
Not easily portable Expensive equipment
The volume of solution/suspension required to administer therapeutic doses of the drug leads to long nebulization times to ensure adequate drug delivery
what are the benefits of breath activated nebulizers vs. regular
Less medication waste Environmental loss and a safer working environment High efficiency Better patient compliance Clinical dose assurance
what is syn respiratory therapy
a treatment in which a substance is introduced into the respiratory tract with inspired air
what are the goals of therapy of syn therapy
Improved strength of respiratory function in a bedridden patient
Bronchodilation in an asthmatic
Liquefication of mucus in a person with COPD
what are the benefits of inhalation therapy
Route of administration is intended to deliver a drug which will produce a direct effect on the lungs Therapeutic concentrations at local sites
Low systemic exposure
Dose can be minimized (mcg vs. mg for oral steroids)
low cost of therapy
indications for respiratory therapy
To provide oxygen in compromised respiratory function (gases)
In general anesthesia (gases)
For systemic dehydration (vapors)
For thinning the mucus (vapors/aerosols) Bronchodilation (aerosols)
Decongestion (vapors/aerosols)
Inflammation (aerosols)
Systemic drug delivery (aerosols) Asthma
COPD
Cystic fibrosis
limitations to inhalation therapy
Dependent on the patients ability to use the device properly (physical limitation, or of the disease)
Variability of the bioavailable dose of the drug (coordination and penetration problems)
Reduced duration of therapeutic effects (lung–>very efficient clearance)
Reduced aqueous solubility of drugs (local irritation/inflammation)
Low intracellular penetration of drugs (for treatment of cystolic pathogens)
what is inertial impaction
Particles larger than 5 µm impact in oropharynx
Have high velocity, as they enter the respiratory tract because of their high velocity they deposit
what is gravitational sedimentation
Desired process
Particles 1-5 µm
Settle onto the airway surfaces during slow, steady breathing or during breath holding
Why we tell our patients to hold their breath upon inhalation: allows for drug sedimentation onto tissue
what is brownian diffusion
Particles <0.5 µm have random motions
Diffuse from aerosol cloud to walls of respiratory tract
what is the optimal particle size
5 micro m
what does efficiency of inhalation therapy depend on (6)
mechanism of particle deposition
Particle size
Patient factors (lung capacity, coordination)
Aerosol container factors (storage, propellant use)
Pulmonary clearance of the drug
Speed of inhalation
How does the speed of inhalation effect efficiency of therapy
Rapid inhalation (disadvantageous): Increase the possibility of deposition by impaction in the oropharynx and the upper large conducting airways Slow steady inhalation (advantageous): Increased number of particles that will penetrate the peripheral portions of the lung Breath-holding (advantageous): Enables the particles to settle into airways under gravity: 10 second breath hold is more efficient than 4 second and 20 seconds provide no additional benefit
what is raoults law
If a mixture of volatile components (propellant and solvents ) exist in a liquefied state, the partial vapor pressure of a propellant at a constant temperature may be approximated by raoults law for ideal solutions Need to create the right pressure because the propellant is in equilibrium between the liquid and gas phase
what is the ideal gas law
○ The pressure of compressed gas aerosols is approximated by the equation of state for an ideal gas
