Aerosols Flashcards
What features of aerosols are desirable in the device?
efficient and quick delivery
dose accuracy
device safety
no special storage conditions to be needed
device should be able to prevent contamination
large supply of doses
device should alert left over doses
cost effective
What is an aerosol?
a dispersion of a solid or liquid (typically <50um) in a gas
-particle size of the dispersed phase can be critical for the proper deposition of drug in lung
What are the advantages of aerosol dosage forms?
directly administered to affected area
rapid onset of therapeutic effect
dosage regulated/metered
single dose (no contamination)
sensitive materials protected
irritation minimized or eliminated
alternate route of administration (fewer AE)
convenient and easy to use
What are the limitations of inhalation therapy?
variability of the bioavailable dose (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
What are examples of aerosolized preparations?
inhalations
-drug administered via respiratory route
insufflators
-“powder blowers” when fine powder is carried into respiratory tract
inhalants
-drugs with a high vapor pressure can be inhaled through the nose
nebulizers
-hospital use
vaporizers
-steam for humidification
What are the types of aerosol devices?
pressurized devices (MDI)
non-pressurized devices
-breath activated inhalers
-nebulizers
What are the components of pressurized aerosols?
aerosol formulation
-propellant
-product concentrate
container
valve and actuator
Describe propellants.
used 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 (CFCs)
non-ozone depleting fluorocarbons (HFA)
hydrocarbons
compressed gases
What should the vapor pressure of propellants be?
low vapor pressure
-liquid at low temp
-gas at room temp
Describe CFCs.
chemically inert
not toxic (may be cardiotoxic or narcotic in very large doses)
non-flammable, non-explosive
non-polar, miscible with non-polar solvents
-immiscible with water
capable of dissolving many substances
gaseous at room temp (liquefied by cooling or compression)
Are CFCs still used?
no, phased out
-ozone depletion
When is the Essential Use Exemptions for CFCs used?
no technically feasible alternatives
significant health/public benefit
no significant release of CFC into the atmosphere
Describe HFA.
alternative to CFCs
non-flammable
non-ozone depleting
chemically inert and toxicologically safe
Describe hydrocarbons as a propellant.
suitable replacement for CFCs
immiscible with water
flammability restricts their use
used in foam and water-based aerosols only
blend of fluorinated hydrocarbons and/or hydrocarbons
Describe compressed gases.
limited value for aqueous products
applicable in topical preparations
What happens as product is used for compressed gases?
volume in container decreases–>pressure in the container drops
=not consistent
What are examples of compressed gases?
nitrogen
nitrous oxide
carbon dioxide
What are the ways the product concentrate can come?
solution
suspension
emulsion
Describe solution systems.
two phases included:
-a solution of active ingredients in liquefied propellant
-vaporized propellant
on activation of the valve the pressure of vapor phases causes the liquid phase containing the drug to rise up in the tube to be expelled from the container
Describe suspension systems.
active ingredient dispersed in the propellant(s)
particle size
particle agglomeration can occur
What does particle agglomeration of suspension systems cause?
valve clogging
inaccuracy of dosing
damage to the container
What can reduce the agglomeration of particles in suspension systems?
surfactants and lubricants
-non ionic surfactants (HLB<10), mineral oil, isopropyl myristate
How is optimal physical stability of suspension systems achieved?
controlling moisture content
particle size reduction
using a dispersing agent
What are the two types of emulsion systems?
foam systems
spray emulsions
Describe foam systems.
propellant in the internal phase (o/w)
-7-10% propellant used
quick breaking foams contain alcohol, water and surfactant
Describe spray emulsions.
propellant in the external phase (w/o)
-containing 25-30% propellant
-no foaming
How are foams produced?
when the product concentrate is dispersed throughout the propellant and the propellant is the internal phase
When are sprays or wet streams made?
when propellant is in the external phase
-foams are not created
What increases the stability of foam preparations?
surfactants
What pressure and temperature must containers be able to withstand?
140-180 psi
55 C
What material is most commonly used for containers?
metal
-tinplated steel
-aluminum
-stainless steel
How are topical preparations for aerosols contained?
in glass
-uncoated
-plastic coated
What are the two types of valves?
continuous valves
metered valves
Describe continuous valves.
medication is dispensed continuously while valve being pressed
-topical preparations
Which type of metered valves contain a dip-tube?
those for upright use contain dip-tube
those for inverted use contain no dip-tube
Describe metered valves.
metering chamber determines volume of product
minimizes administration errors
inhalation devices are mainly metered valves
improved delivery into nasal passageway and resp tract
What is the limitation of metered valves?
considerable product loss during actuation
Describe product loss from MDIs.
~10% lost to the inner surface of the adapter
-even when best technique is used, may only get 25% of what comes out of the MDI into your lungs
-most people only get 15% from each puff
still it is enough for therapeutic action
What is the use of inhalation aids?
typically used for MDIs
measure dose is released into a spacer device
spacers enhance efficacy of the medicine and ease coordination
spacers trap large particles of the spray so they dont land on the mouth (minimizes infection)
Describe the Respimat.
soft mist-non pressured MDIs
devices are pre-loaded with solution of medication
uses spring to deliver soft mist of medication
Describe breath-activated powdered inhalers.
devices are pre-loaded with pure drug within the device (Turbuhaler)
Handihaler: activation pierces the capsule, releasing med
Diskus:deep breath is required for inhalation
What is unique about the Genuair?
feedback mechanisms to reassure patients that the dose has been taken correctly
What are the advantages of MDIs?
portable, light, and compact
compatible with inhalation aids
multiple dose convenience
reproducible dosing
difficult to contaminate
What are the disadvantages of MDIs?
considerable product loss (high oropharyngeal deposition)
hand-breath coordination required
proper inhalation, breath holding is required
reaction to propellants is possible
difficult to determine remaining doses
What are the advantages of DPIs?
no inhalation aid coordination
some can be checked if full dose was inhaled
built in dose counter
no CFCs/propellants
What are the disadvantages of DPIs?
variable inspiratory flow rate causes variability of dose
loss of dry powder in capsule, inhaler and oropharynx is high
gritty sensation/taste
some affected by humidity
some may be irritating (lactose fillers)
less effective in acute situations
requires adequate inspiratory drive
What is the limitation of the Respimat?
cost and need for priming
What is the advantage of the Respimat?
reduces the requirement for patient coordination and inspiratory effort
higher lung deposition and lower oropharyngeal deposition
What are nebulizers?
device that uses a compressor to aerosolize liquid medication
What is the major advantage of nebulizers?
less dependent on patient coordination
effective for infants and children
Describe inhalation of drug from a nebulizer.
drug inhalation by normal tidal breathing
over a 5-10 minute period
flow of gas is 6-8L/min
Where is the diluted medication contained in a nebulizer?
nebulizer unit
How is medication inhaled with a nebulizer?
mouthpiece or face mask
How is aerosol generated in a nebulizer?
compressed air/oxygen (jet nebulizers)
ultrasonic waves (ultrasonic nebulizers)
Who needs nebulizer therapy?
very young, very old, debilitated, or distressed patients
when combination of compatible meds is intended
where patient coordination is compromised (COPD or asthma exacerbation)
long-term bronchodilator treatment of chronic airflow obstruction
prophylactic drug treatment for asthma
antibiotics for CF, bronchiectasis and HIV/AIDS
symptom relief in palliative care
What are the disadvantages of nebulizers?
not easily portable
expensive equipment
volume of solution/suspension required to administer therapeutic doses of the drug leads to long neb times
Describe a jet nebulizer.
pressurized jet air stream enters through a narrow tube and is forced through a narrow opening (venturi)
jet stream causes a pressure drop near the venturi
decreased pressure (vacuum effect) 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
Describe ultrasonic nebulizers.
produce aerosolized droplets using high-frequency sound waves
droplet size determined by frequency of sound waves
What is the preferred method of delivery for nebulizers?
mouthpiece
-delivery increases by up to 85%
Describe the face mask as a method of nebulizer delivery.
drug in contact with skin; wash face after admin
only means to administer drug to infants
What is respiratory therapy?
a treatment in which a substance is introduced into the respiratory tract with inspired air
intended to deliver a drug which will produce a direct effect on the lungs
-therapeutic drug concentrations at local sites
-low systemic exposure
-dose can be minimized
-low cost of therapy
What are the indications of inhalation therapy?
provide O2 in compromised lung function
-gases
general anesthesia
-gases
bronchodilation
-aerosols
decongestion
-vapours/aerosols
inflammation
-aerosols
systemic drug delivery
-aerosols
cystic fibrosis
Describe cystic fibrosis.
caused by genetic mutations
salty-tasting skin
cough with sputum production
chronic airway infections
recommended device=nebulizers
Describe the different respiratory structures.
pharynx
-smooth muscle cells
-voice box, respiratory passage way
trachea
-cartilaginous rings connected by smooth muscle
bronchi
-division of trachea
-same structure as the trachea
respiratory bronchioli–>alveolar sac–>alveoli
-transfer of gases between air and blood
-secretes surface-active substances
-defence: alveolar macrophages
-alveolar wall: epithelial layer, basement membrane, endothelial lining of the capillary
What does the efficiency of inhalation therapy depend on?
mechanisms of particle deposition
particle size (1-5um diameter)
speed of inspiration
patient factors (lung capacity, coordination)
aerosol container factors (storage, propellant use)
pulmonary clearance of drug
What are the three mechanisms of drug deposition in the lungs.
inertial impaction
-larger (>3um), fast-moving particles
-larger particles filtered in the nose and/or oropharynx
gravitational settling
-function of particle mass and time, rate of settling proportional to particle size and mass
diffusion
-particles smaller than 1um
What size of particles reach the proximal generations of the lower respiratory tract? What size reach the lung periphery?
5-10um
1-5um
What is MMAD?
mass median aerodynamic diameter
-the particle size (in um) above and below which 50% of the amount of drug is contained
-higher MMAD, the more particle sizes are of larger diameters
What is the impact of speed of inhalation on inhalation therapy?
rapid inhalation (disadvantageous)
-increased possibility of deposition by impaction in the oropharynx and 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
List the particle size that deposits in the following structures:
-oropharynx
-large conducting airways
-small conducting airways and alveoli
-lungs
oropharynx: >10um
large conducting airways: 5-10um
small conducting airways and alveoli: 1-5um
minimally deposited in lungs: 0.1-1um
Describe proper inhaler use.
breathe out a normal breath
position the head tilted slightly back
inhale one dose by a deep and slow breath
-closed mouth technique preferred
hold breath for at least 10s
breathe out a normal relaxed breath
-if two doses required–>30s between doses
What are the patient related factors and clinical factors in selection of right delivery device?
age
physical and cognitive ability
respiratory rate and lung volume
inability for a deep breath (DPIs not a good option)
patient preference
cost and reimbursement
frequency of therapy, routine vs intermittent
rescue meds need portability
What are the drug-related factors in selection of right delivery device?
availability of drug in more than one form
combination of aerosolized treatments (one device increases compliance)
ease of use, limited treatment time, portability, cleaning and maintenance
good durability so that it can withstand rigorous treatment and cleaning procedures every day
What is Raoults Law?
applies to liquefied gas systems
if a mixture of volatile components exists in a liquefied state, the partial vapor pressure of a propellant at a constant temp may be approximated by Raoults Law
-pi=pi (H) x xi
-pi=partial pressure of component in mixture
-pi (H)=vapor pressure of the pure component
-xi=mole fraction of component
What is the ideal gas law?
the pressure of compressed gas aerosols by the equation of state for an ideal gas: pV=nRT
p=pressure
V=volume
n=number of moles of gas
R=universal gas constant
T=temperature
What are the factors affecting MDI performance?
shaking before use
-no shake=decreases total and respirable dose by 25-35%
temperature
-outdoor use=decreases aerosol drug delivery
-effect is propellant dependent
nozzle
-inner diameter of nozzle is inversely proportional to amount of drug deliver to patient (<1mm increases delivery)
-cleanliness and presence of moisture
-white and crusty residue due to crystallization
timing between actuation
-rapid actuation of >2 puffs=turbulence+coalescence of particles=reduce drug delivery
-wait one minute between actuations
priming
-product specific (Ventolin=>5 days, Flovent=>1wk)
patient characteristics
-age and technique
Describe proper MDI technique.
closed mouth technique preferred
1. remove mouthpiece and shake
2. prime
3. sit up straight or stand
4. breathe out
5. place MDI in mouth
6. seal lips
7. actuate MDI and breathe in slowly
8. hold breath for 10s
9. wait one minute if another puff is needed
if taking corticosteroid, rinse mouth after
What is the preservative in Combivent Respimat?
benzalkonium chloride
What are some important points regarding preparation of a Respimat?
do not remove cartridge once it has been inserted
discard date is 2-3 months from date cartridge is inserted
inhaler should not be taken apart after cartridge is inserted
What kind of devices come as dry powder inhalers?
turbuhalers
breezhalers/neohalers
handihalers
diskus
genuair
ellipta
What are the factors affecting DPI performance?
inspiratory flow
-higher inspiratory flow required to deaggregate powder into finer particles
-excessive flow increases impaction on the oral cavity and thus decreases total lung deposition
moisture
-can lead to powder clumping
-single dose DPIs offer better protection than multi-use
-exhaled air into mouthpiece can impact (exhale away)
Describe proper turbuhaler technique.
open the cap
turn the dial to the right and then left until a click
exhale away from device
seal lips around device and inhaled deep + strong
hold breath
rinse mouth
Describe proper handihaler technique.
release the dust cap
open mouth piece
insert a capsule
close mouthpiece and pierce the capsule
breath out
inhale deeply and strongly
should vibrate if rate is sufficient
discard old capsule before putting in new one
Describe proper Diskus technique.
twist the cap to expose mouthpiece
push on the liver until a click to load the dose
exhale away and then take a deep breath
hold breath for 10s
close cap
What does it mean if a dose window for the Diskus is red?
less than 5 doses left
What is an advantage of the Ellipta?
can mix two different drugs
Describe proper Ellipta technique.
remove from tin foil
load dose by sliding the cover down until a click
exhale away from the device
inhale deeply and strongly
What can go wrong with DPIs?
inadequate inspiratory flow
improper assembly of loading of the device
DPIs not clean and dry (use dry cloth for cleaning)
puncturing of capsule not adequately performed
exhaling into the DPIs (introduces moisture)
tracking the remaining doses
