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
