Inhaled Route of Delivery: Dry Powder Inhaler Flashcards
How do they deliver to the drugs?
Moves over static powder bed then fluidised
Fluidised particles aggregated by strong aerodynamic force
Enters airway + drug separates from carrier
Where the particles go if they are larger?
Throat
Where will the particles go if they are smaller?
Deep into respiratory tract
What happens if deep sharp breath?
Increased turbulent air
= increased inertial impaction
What happens if controlled respiratory flow rate?
Drug move slower + follow air flow to lower respiratory tract
What size are micronized powders?
2-5 micrometres
Why must they be shaken?
Powders never completely homogenous
= affect dose uniformity
What does micronization do?
Reduce drug size
Improve homogeneity + control particle size
How is micronization achieved?
Jet milling
Describe jet milling
Material fed into shallow circular grinding chamber
High velocity
Turbulence = particle bombarding
= larger particles concentrated at periphery of chamber
Finer particles leave with air stream
What are the powder factors to consider when formulating DPIs?
Crystallinity
Hygroscopicity
Polydispersity
Aerodynamic diameter
What is crystallinity?
Packing within structure
= increased packing = increased stability BUT decreased dissolution
What happens in crystallinity?
Powders transfer to lower energy state
Choose most stable polymorph
What is hygroscopicity?
Ability to take up moisture
What happens in crystallinity?
Take up moisture
= disrupt crystal structure
= effect dissolution profile + crystallisation
What is polydispersity?
Range of particles around the mold
What happens in polydispersity?
Inhaled powders = multi-modal
= NOT all particles all same size
= poly dispersed
What is aerodynamic diameter?
Influence where particle lands in lung
Why is lactose used?
Decrease drug cohesiveness
Describe what happens with excipient lactose
Drugs adhere to larger carrier particles by weak electrostatic forces
Particles fly off larger carrier particles
Carrier deposits + remains in mouth
Still feel powder left in mouth
What does adhesion + detachment depend on?
Morphology of particle surfaces + surface energies
What can a carrier with rough surface do?
Hold micronized drug too strongly during storage
= increase overall aerodynamic size
What can a carrier with smooth surface do?
Increased dispersion during inhalation
BUT may not stay mixed
What is an approach to smooth vs rough surface?
Mix rough carrier particles first with micronized carrier then with micronized drug
= drug free to detach
What is the aim of powder mixing?
Achieve homogeneity
What is the major challenge?
Inhaler resistance + inspiratory flow rate
What happens when a patient inhales?
Diaphragm generates decreased pressure
= air flow
How is increased flow rate achieved?
Decreased resistive device
What happens if there is a narrow inlet?
Increased turbulence
Rapid airflow
= deposition in the throat
What happens if there is narrow flow stream?
Increased velocity
= increased improvement to device performance
What happens if there is high resistance?
Better performance
What is the problem with high resistance?
Paediatric + elderly patients may have difficulties with insufficient IFR
Why is a rapid airflow required?
Increases particle deagglomeration
BUT at same time increase oropharyngeal deposition + reduce dose delivered to drug
What can DPIs be?
Unit-dose or multi-dose
Describe Spinhaler
Contains sodium cromoglicate
1st DPI
Unit-dose
Describe how each dose in Spinhaler is contained?
In hard gelatin capsule
Placed individually into device prior to use
Describe how the Spinhaler works
Capsule pierced by 2 metal needles
Inhalation = air flows = turbulence flow as rotor rotates
Powder dispersed to capsule wall + out into inspired air
Through perforations
What does the HandiHaler contain?
tiotropium bromide
Unit-dose
Describe Accuhaler
Multi-dose
Describe the dose in Accuhaler
Drug preloaded = 60 doses
Each dose packed separately = exposed to ambient conditions
What is problem to Accuhaler?
Insensitivity to humidity
Describe how the Turbohaler (Symbicort) works
Drug flows on rotating disc unit
Excess removed by scarpers
Describe the doses of Turbohaler (Symbicort)
200 doses of undiluted, loosley aggregated micronized drug
What is not needed in the Turbohaler (Symbicort)?
No carrier
No individual dose loading
What does the Turbohaler (Symbicort) require?
High inspiratory effort due to high internal resistance
What is the problem with Turbohaler (Symbicort)?
More sensitive to humidity
Because the Turbohaler (Symbicort) requires high inspiratory effort what does this mean?
May not be suitable for kids or elderly
What are breath-assisted devices designed to do?
Reduce or eliminate reliance on patient’s inhalation effort to disperse the drug
When are breath-assisted devices useful?
Patients who can only achieve low inspiratory flow rates
What is an example of breath-assisted devices?
Spiros
What was Spiros?
DISCONTINUED
Effort-assisted device using a battery-powered impeller to deaggregate + aerosolise the drug powder
