RMS-1 Quiz Inhaler Technology Flashcards
What does the central airways consist of
Trachea, primary bronchus, secondary bronchi
What does the peripheral airways consist of
Tertiary bronchi, respiratory bronchioles and alveolar regions
Is the left or right bronchi wider
THE RIGHT
How does the function of the respiratory tract change
Upper airways = air movement
Lower airways = gaseous exchange
How many divisions are there from the trachea to the alveoli
23
Why is it highly likely for particles to be deposited on airway walls
The airways follow a very tortuous pathway
What size to particles have to be to reach
a) bronchioles
b) alveolar sacs
a) <5 microns
b) < 2 microns
Describe where
a) large (coarse) particles will be deposited
b) small (fine) particles will be deposited
a) mouth and the back of the throat - high deposition in the central airways
b) wide distribution to the respiratory bronchioles and alveoli
What is inertial impaction
Mechanism of deposition for larger particles (>5 micrometers), with sufficient momentum they will impact the airway walls. Further into the lungs the velocity of airstream decreases so this mechanism becomes LESS important
What happens if a particle escapes impaction
Settling will occur via gravitational sedimentation, for particles 1-5 microns (same thing as micrometers)
What does gravitational sedimentation depend on
Particles size and density - Stoke’s law (particle settling under gravity will have a constant terminal settling velocity)
What’s Brownian diffusion
Mechanism of deposition, where particles collide with surrounding gas molecules and randomly move along the airways . They diffuse from a high con to a low - diffusion is inversely proportional to particle size. Predominant mechanism for particles <1micrometer
How are particles cleared from the airways
1) particle deposited on the airways
2) drug particle dissolves in the mucus and absorbs across the epithelium
3) insoluble particles in the central part of the lung are cleared by mucocilliary clearance or macrophages
4) particles in the alveolar region are cleared by alveolar macrophages
What are the pros about local delivery for inhaler/nebulisers
They will have a high local availability and therefore low systemic exposure as treatment is contained to a certain area
What are the pros about systemic delivery for pulmonary conditions
Rapid pharmacokinetics and it avoids the first pass metabolism (e.g. injection/IV)
What are some drug classes useful to treat pulmonary conditions
Bronchodilators, steroids, antibiotics, pulmonary vasodilators
What are the different types of inhalers
Pressurised metered dose inhaler
Dry powder inhaler
Nebulisers
What’s the difference between obstructive and restrictive diseases
Obstructive = airways are narrowed or blocked making it hard to EXHALE
Restrictive = lungs can’t expand properly (stiff lungs) making it hard to INHALE
Examples of
a) obstructive
b) restrictive
Diseases
a) asthma, COPD, emphysema, chronic bronchitis, cystic fibrosis
b) obesity, muscular dystrophy, fluid in the lungs, pulmonary fibrosis
What are the 2 types of nebuliser
1) jet/ pneumatic nebuliser
2) ultrasonic nebuliser
What’s an advantage of breath actuated nebuliser
Very little drug wasted
What’s the advantage of an electronic vibrating mesh
Small, portable and very little drug wasted
What’s special about adaptive breath controlled nebulisers
The mouthpiece causes resistance to control the inspiratory rate and its breath actuated
Advantage of metered dose liquid inhalers
Breath actuated, very little drug wasted, optima, drug deposition and extremely high dose reproducibility
What are the conditions for nebulisers
Must be sterile, isotonic, stable over shelf life, within physiological pH range (5-8), fre from particulates (for liquid solution only) and particle size must be within respirable range (3-5microns - for liquid suspensions only)
Advantages of nebulisers on general
High aerosolisation efficiency, high deposition efficiency, used for all ages and no formulation requirements
Disadvantages of nebulisers
Expensive, shelf life and most are not portable
Name 4 key components in a PMDI
Aerosol canister, drug suspension/solution, metering valve and aerosol spray cone
What are the 2 hypotheses for atomisation
Internal flash evaporation and aerodynamic breakup
What propellants are used for pMDIs
HFA 134a and HFA 227
Advantages and disadvantages of propellants
Adv: non-flammable, non-toxic and do not deplete the ozone layer (but they still contribute to global warming)
Disadv: low aqueous and lipid solubility making it difficult to formulate
What are HFA & the regulations linked to them
Non-ozone depleting gases
Because they contribute to global warming control of HFA production for non-essential items is put in place HOWEVER inhalers are considered essential so it’s fine <3
What are the technical problems associated with HFAs
1) suspension stability - surfactants are insoluble in HFA (alcohol is required as a co-solvent this changes taste I
And is haram)
2) valve material incompatibility materials may react with the co-solvent used in HFA pMDIs = impaired valve performance
3) moisture - HFA has a high affinity to moisture and even more so with the alcohol co-solvent = increased chemical instability during storage = decreased bioavailability of drug due to deposition on the walls of the apparatus
What properties must drug particles in a pMDI must have
Must be MICRONISED
target size is 1-5microns
Do suspensions or solutions have drugs with HIGH solubility in HFA propellant
SOLUTIONS = high
(Suspensions = low)
Do suspensions or solutions have drugs with some spray droplets will be drug-free
SUSPENSION OBVS
(All droplets in solution will contain the drug)
Do suspensions or solutions have drugs with high chemical stability
SUSPENSIONS
( solution = chemical stability may be a problem)
Do suspensions or solutions have drugs that may clog the spray exit
SUSPENSIONS OBVS
(Solution = no clogging)
Do suspensions or solutions have drugs which may cause caking or flocculations problems
SUSPENSIONS BC ITS NOT MIXED
(Solution = no caking or flocculations problems)
What co-solvent may be used in pMDIs
Alcohols = ethanol, or glycerin
What surfactants may be used in pMDI formulation
Oleic acid, lecithin, cetylpyridium and sorbitan
What do spacers achieve
- they provide extra time for the propellant to evaporate
- they reduce droplet velocity = reducing drug impact in mouth and throat
- catches larger droplets/particles so they don’t deposit in the mouth/back of the throat
-breath coordination is not required
-multiple inhalation can be taken
Key patient tips for pMDIs
- shake before use
- require priming
- slow and steady inhalation
- hold breath after
-use a spacer where possible
What are the advantages of and Disadv of dry powder inhalers
Adv:
No CFs
Breath actuated no need to coordinate breath with inhaler
High dose can be delivered
Disadv:
Complex
What is the difference between active and passive DPIs
Passive = relies on patient inhalation to aerosolize the powder (has particle carriers only)
Active= uses a power source to disperse the powder, good for weak lungs (particle with carrier or carrier free particles)
What’s the main advantages of passive inhaler compared to active ones
Passive is small and portable, inexpensive, compact
What’s the peak inspiratory flow rate, PIFR
Maximum airflow (litres per minute) produced by inhalation of patient
What’s the average PIFR
150L/min
Would similar inspiratory efforts produce different flow rates, drug dispersion and deaggregation in different inhalers
YES
Does high resistance device = low efficiency
No high resistance usually means the powder is dispersed better
What are the components in carrier particles
Lactose = carrier + micronised drug = ordered mix
What’s happens to drug particles that are too large
Deposited in the mouth and the throat doesn’t reach the respiratory tract
What’s the main advantage of active inhaler devices
High aerolisation efficiency dependant of the patient inspiratory effort
What features would be ideal in a carrier particle
Smaller, round, smooth, add force control agents
Equation for aerodynamic diameter of particle, da
da = dg (geometric diameter of particle) X p (density of particle)^ 0.5
Look at the twin stage impinger
Look at Anderson cascade impactor
Look at multi stage liquid impinger
Look at new generation impactor
Equation for recovered dose (RD) %
= (drug recovered from packaging + inhaler + evaluation device (mg or micrograms))/ original drug dose (mg or micrograms) X 100
Equation for total emitted dose ED %
(Drug recovered from packaging + inhaler + evaluation device (mg or micrograms))/ recovered dose X 100
Equation for fine particle dose/ fine particle fraction / respirable dose (% < 5 micrometers) (FPF%)
(Drug recovered from the TSI lower chamber or ACI stage 3-7 + filter (mg or micrograms) / recovered dose (mg or micrograms) X 100
What’s the mass median aerodynamic diameter in micrometers, MMAD
Median particle size of a log normal particle distribution curve derived from the mass of drug depositing on each stage of the ACI, NGI or MLI
What’s the geometric standard deviation
Square root of ( 84% undersize value in micrometers / 16% undersize value in micrometers)
What are the bp test required
1) uniformity of delivered dose
2) aerodynamic assessment of fine particles
What are the 5 factors that influence lung deposition (be prepared to explain in detail not here but in the exam)
1) particle size
2) particle size distribution
3) particle density
4) particle shape
5) hygroscopicity
