Why motivated the development of dry powder inhalers? DPIs
Phasing out of CFC's and the idea of no propellants
What are some broad advantages of DPIs
No coordination required with actuation, increased stability, dosing advantages
What particle sizes will get stuck in the oropharyngeal region?
Why do particles get stuck in the oropharyngeal region?
inertial impaction--airflow stream separates out very large particles
What is the term of particles stopping in the trachea?
Sedimentation occurs to what size particles?
What size particles go make it to the alveolar region?
< 1 µm
What happens to particles that enter the alveolae?
What happens to particles that are smaller than 0.5 µm?
Brownian motion prevents deposition of particles unless the breathis held a LONG time
What is considered the good particle range size?
between 0.5 and 5 µm (0.5 < good < 5 µ)
What four characteristics of particles affect deposition?
(2) deposition by image charges in airways
Shapes that are
seriously deviant from sphericity effects deposition
deposition in the lungs which are at high humidity due to increased particle size from water absorption
What is the characteristic of asbestos?
Long,thin needles are aerodynamically small but sticky
What is the mechanism behind fluidization of powders?
What two factors affect fluidization?
(1) particle size
(2) varying attractive forces between particles
Why does chalk stick on the blackboard?
van der Waals forces overpower gravitation allowing for adhesion
What are carrier particles used for?
Lactose is used because it is large enough to be fluidized and very small particles will adhere to it
What is the magnitude of vdw?
10^9 - 10^7
What is the magnitude of electrostatic?
10^18 - 10^10
What is the magnitude of capillary?
10^7 - 10^6
T/F Adhesions forces are material dependent
True (mechanical interlocking/solid bridging from irregular shapes)
How does capillary force affect adhesion?
moisture builds a liquid bridge
What are the 4 steps in drug delivery?
What are the two types of metering?
(1) pre-metered (capsule, blister)
(2) metered during application
Which methods require active drug delivery?
(1) pressurized air
(2) Piezo vibration
When are all CFC inhalers gone?
What's the difference between passive and active DPI's?
Passive rely on patient to provide energy. Active uses an outside energy source
What size lactose is used as a carrier?
What is entrainment?
What is the most common carrier in DPI formulation?
Why is lactose used?
increased size aids in entrainment, descreases deaggregation, improves powder flow
What is a disadvantage of lactose?
Inefficient detachment of drug from lactose carrier
Benefits of DPI's
(1) Higher dose delivery
(3) no propellants
(4) ++ compliance
(5) ++ lung deposition
(6) wide range of therapeutics (proteins and peptides)
Disadvantages of DPI's
(1) low formulation flexibility
(2) inspiratory effotr still necessary
(3) dose dependency on flow rate
(8) excipients few and few FDA approved
What are the comliance issues converning DPI?
(1) advantages: portable, reusable, dose counters
(2) disadvantages: reloading, multiple operation steps (complexity)
What are the two tested DPI excipients
What is the preferred patient delivery method?
Multiple dose, factory metered (blister repack, ease of use!)
What aspects affect DPI formulation?
(1) physical powders properties
(2) approaches to realize required aerodynamic diameter
(3) drug factors
(4) mositure protection
List some physical powder properties
(1) aerodynamic diameter (size + density)
(2) ashesion/cohesion (surface charges, etc)
(3) flow properties (metering accuracy)
(4) hydroscopicity (stability, metering)
How do protect against moisture?
(1) blister packing
(2) device design
Describe characteristics of the Diskus
30 doses but only 10-15% lung deposition, looks cool
What is the fine particle fraction of twist inhalers?
What made the skyehaler unpopular?
Had to be verticle when loading
Describe the cost, complexity, performance of passive dispersion
Cost=low Complexity=low, mod Performance = flow rate dependent
Describe the cost, complexity, performance of active dispersion
Cost=high Complexity=mod, high Performance = Independent of flow rate
Advantages of factory metering
(1) increased accuracy
(2) dose protection
(3) in process controls
(4) metering is patient independent
Disadvantages of factory metering
(1) production efficiency (many discarded doses)
(2) reloading unit dose systems difficulty
Advantages of device metering
(1) Production efficiency
(2) multiple doses!!!!
Disadvantages of device metering
(1) Metering is patient dependent
(2) high dose variability
(3) component tolerance
(4) dispension variation
(5) inprocess control
(6) poor moisture protection
T/F Patients prefer single dose inhalers
False (multidose preferred)