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PHAR 224 > Aerosols > Flashcards

Aerosols Flashcards

1
Q

what is an aerosol

A

An aerosol is a dispersion of solid or liquid particles (typically <50 micrometers diameter) in gas

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2
Q

How does an aerosol work?

A
  1. Pressing on the actuator allows the product to come out through the valve
    1. Contents are a combination of ingredients and propellant specifically formulated to form the products specific job
    2. 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
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3
Q

what are uses of respiratory therapy?

A

asthma, rhinitis, cystic fibrosis, COPD

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4
Q

What are 3 things to consider when developing a device?

A

API properties
Properties of the device
Site of action

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5
Q

what are API properties to consider

A

molecular weight
charge
solubility
lipophilicity

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6
Q

What are formulation properties to consider

A

disintegration
dissolution
particle size
wettability

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7
Q

what are some properties of the site of action (lungs)

A

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

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8
Q

what are advantages of aerosols

A

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

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9
Q

what is propellant

A

To develop the proper pressure within the container
Expel the product
Aid in atomization or foam production

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10
Q

what are the types of propellants

A

Chloro-fluoro hydrocarbons
Non-ozone depleting fluorocarbons
Hydrocarbons
Compressed gasses

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11
Q

what are the characteristics of CFCs

A 
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
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12
Q

what are the characteristics of non-ozone depleting fluorocarbons (HFA)

A

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

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13
Q

what are the characteristics of hydrocarbons

A

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

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14
Q

How CFC, HFA and HC work

A
  1. 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)
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15
Q

what are the characteristics of compressed gasses

A

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

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16
Q

what are the components of aerosols

A

Propellants
Product concentrate
Container
valve and actuator

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17
Q

Different types of product concentrate systems

A 
Solution systems (2 phase) 
Suspension systems 
Emulsion systems (3 phase)
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18
Q

what is a solution system

A

Solution of active ingredient in pure propellant
Equilibrium between the liquid propellant (and drug) and the propellant vapor
Alcohols: auxiliary solvent

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19
Q

what is a suspension system

A

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

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20
Q

what is the issue with solution and suspension systems

A

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)

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21
Q

what are ways to ensure physical stability of suspension and solution systems

A

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)

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22
Q

what are the 2 types of emulsion systems

A

Foam and spray emulsions

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23
Q

what is a foam system

A

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

24
Q

what is a spray emulsion

A

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

25
Q

what are the materials often used in containers for aerosols

A

Metal: most commonly used (aluminum reacts with CFCs)
Glass: preferred as it is inert compared to metal

26
Q

what are the types of valves used?

A

continuous and metered

27
Q

what is one important thing to consider when choosing materials for the valve and actuator

A

Need to ensure the ingredients are compatible with all the components (rubber, metal) to make sure it doesn’t corrode

28
Q

how do continous valves work

A

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

29
Q

what are metered valves

A

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)

30
Q

how do metered valves work

A

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

31
Q

what do spacers do

A

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

32
Q

what is a DPI?

A

Devices are pre-loaded with pure drug within the device
Actuation: twisting the bottom of the device
Operation of inhaler based on patient inspiration

33
Q

advantages of DPIs

A

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

34
Q

Disadvantages of DPIs

A

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

35
Q

Special things to know about turbuhalers

A

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

36
Q

what is a nebulizer

A

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

37
Q

what is an advantage of nebulizer therapy

A

less dependent on patient coordination or cooperation

38
Q

who needs nebulizer therapy

A

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

39
Q

How does a compressed air/oxygen (jet nebulizer)

A

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

40
Q

how does a ultrasonic nebulizer work

A

produce droplets using high-frequency sound waves

droplet size is determined by the frequency of the sound waves

41
Q

advantages of nebulizers

A

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

42
Q

disadvantages of nebulizers

A

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

43
Q

what are the benefits of breath activated nebulizers vs. regular

A 
Less medication waste 
Environmental loss and a safer working environment 
High efficiency 
Better patient compliance 
Clinical dose assurance
44
Q

what is syn respiratory therapy

A

a treatment in which a substance is introduced into the respiratory tract with inspired air

45
Q

what are the goals of therapy of syn therapy

A

Improved strength of respiratory function in a bedridden patient
Bronchodilation in an asthmatic
Liquefication of mucus in a person with COPD

46
Q

what are the benefits of inhalation therapy

A

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

47
Q

indications for respiratory therapy

A

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

48
Q

limitations to inhalation therapy

A

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)

49
Q

what is inertial impaction

A

Particles larger than 5 µm impact in oropharynx

Have high velocity, as they enter the respiratory tract because of their high velocity they deposit

50
Q

what is gravitational sedimentation

A

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

51
Q

what is brownian diffusion

A

Particles <0.5 µm have random motions

Diffuse from aerosol cloud to walls of respiratory tract

52
Q

what is the optimal particle size

A

5 micro m

53
Q

what does efficiency of inhalation therapy depend on (6)

A

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

54
Q

How does the speed of inhalation effect efficiency of therapy

A 
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
55
Q

what is raoults law

A

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

56
Q

what is the ideal gas law

A

○ The pressure of compressed gas aerosols is approximated by the equation of state for an ideal gas

PHAR 224 (7 decks)

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