Inhalation Product Design Flashcards
What must be considered in inhaler design?
Right dose delivered
Aerodynamic particle
Patient + clinician acceptability
Cost
Ease of use
What is the most suitable particle size?
2-5 micrometer
What are the scientific challenges?
Poor site targeting
Poor intracellular delivery
Toxicology
Poor in vitro-in vivo correlation
Formulation instability
What does in vitro study determine?
Performance in a controlled environment outside of a living organism
Describe the process for designing a new inhalable
Fully characterised drug formulation
Device selection
Dose retrieval
Characterisation post aerosolisation
Bioactivity pre/post aerosolisation
Breathing simulator studies
In vitro bioactive inhaled therapeutic
In vivo studies
What are the BP tests for inhaler devices?
Uniformity of delivered dose
Fine particle dose
Aerodynamic particle size distribution
Number of deliveries per inhaler
Effectiveness of antimicrobial preservative
Leakage (pMDIs)
What does the uniformity of delivered dose ensure?
Consistency of the dose emitted + fine particle mass throughout the life of container form
What do DPIs rely on?
Patient’s inspiratory flow rate than propellant for dose emission
What is fine particle dose?
Amount of delivered dose that lies below 5 micrometre cut-off
How is fine particle dose determined?
In parallel to aerodynamic particle size distribution
What does aerodynamic particle size distribution determine?
Where the API is deposited
What is the fraction that is deposited in the lung referred as?
Fine particle fraction (FPF)
What is the optimal size for peripheral airway deposition?
Upper limit = 5 micrometre
Lower limit = 1 micrometre
How do cascade impactors work?
Comprise a series of progressively finer jets + collection plates
Separate particles on basis of particle inertia
Describe cascade impactor operation
Samples drawn into impactor flowing
Nozzle size + area decrease with stage number
Particles remain or break through lines of flow
Particles with sufficient inertia collected rest pass on to next stage
What are the different cascade impactor designs?
Glass impinger
Multi-stage liquid impinger (MSLI)
Andersen cascade impactor (ACI)
Next generation impactor (NGI)
What are glass impingers used to test?
pMDIs
DPIs
Nebulisers
What is problem with glass impingers?
Limited info regarding particle size
= 2 stages
Particles collected in throat of glass impinger considered?
“Non-respirable” = NOT inhaled into lower respiratory tract
Particles collected in lower impinger considered?
“Respirable”
What does MSLI test?
DPIs
pMDIs
Describe MSLI
4 stages with filter terminal
How are the collection stages kept in MSLI?
Moist
= eliminates particle bouncing off the collection plate
Describe ACI
8-stage cascade impactor
What does the ACI test?
MDIs
DPIs
What are the advantages of ACI?
Easy to handle stack-up design
Damaged stages can be replaced
Describe NGI
Cups rather than plates
7-stages
What rate does NGI operate between?
15-100 L/min flow rates
What does the NGI test?
pMDIs
DPIs
Nebulisers
Describe the number of deliveries per inhaler BP test
Take an inhaler + discharge the contents to waste until empty
What are the requirements of number of deliveries per inhaler BP test?
Total number of deliveries discharged from inhaler must not be less than number stated on product label
Describe the efficacy of antimicrobial preservative BP test
Preservative properties adequate
= significant fall or no increase in number of micro-organisms
What is the formulation for leakage pMDIs BP test?
Solution/suspension
What is the requirement for the leakage pMDIs BP test?
Not more than 10% of the nominal fill mass of the container over entire shelf life
What is used in uniformity of delivered dose test + why?
Critical flow controller to allow adjustable flow + inhaled vol
Why is breathing pattern important?
Determines amount of API available for the patients
What is the uniformity of delivered dose test based on?
Standardised tidal flow conditions generated by breath simulator
