Module 2F Pulmonary Drug Delivery Systems Flashcards
Define: hygroscopic growth (2)
Humidity causes aerosol particles to absorb or evaporate water changing its size, morphology and phase resulting in deposition higher in the respiratory tract than predicted
Define: aerosol (3)
A two phase system of solid particles or liquid droplets dispersed in a gas phase having small enough partials dispersed in air or gaseous phase that is small enough to be stable as a suspension.
Discuss the potential advantages of delivering drugs via the respiratory tract (6)
- Rapid onset of activity
- Smaller doses
- Useful when drug is poorly absorbed orally
- Useful when drug is rapidly metabolised orally
- Avoidance of first pass metabolism
- Systemic activity
- large surface area
- abundance of capillaries
- thinness of the air-blood barrier
List the mechanisms which molecules are deposited in the airways (6)
Particle deposition in airways:
1. Gravitational sedimentation
- dependent on size, density and resistance time in the airways
2. Inertial Impaction
- airstream changes direction causing particles to have a high
momentum - used for deposition in the nose, mouth, pharynx
and larynx
3. Brownian diffusion
- collision and bombardment of small particles by molecules in
the respiratory tract produces Brownian motion. High to a low
concentration therefore diffusion occurs and is inversely
proportional to particle size
4. Interception
5. Electrostatic attraction
6. Patient factors
Describe clearance of inhaled particles deposited in the airways (5)
Cleared within 24hrs and ultimately swallowed.
Insoluble particles penetrating to the alveolar regions are removed slower by alveolar macrophages. They engulf particles and may migrate to the mucociliary escalator or removed via the lymphatics.
“Different deposition mechanisms are important for different sized particles” discuss this statement (4)
Depending on the size of the molecule the particles will be deposited in different parts of the respiratory tract.
Eg:
1. >5um deposited by inertial Impaction in the upper airways
2. 1-5um deposited by gravitational sedimentation in lower airways
3. <1um deposit by Brownian diffusion in stagnant of air lower airways
4. ~0.5um are inefficiently deposited (exhaled) too large for effective
deposition by Brownian diffusion and too small for effective
Impaction
or sedimentation
Describe the influence of environmental humidity on particle size (5)
- As a particle enters the respiratory tract, the change from ambient to
high humidity results in condensation to form on the particle surface - Water insoluble materials: results in a negligibly thin film of water
- Water soluble materials: solution is formed on particle surface -> the
particle will increase in size
-> hydroscopic growth: resulting in particles being deposited higher
in the respiratory tract
What are formulation considerations for suspension preparation MDI’s (7)
Solution preparations:
Are 2 phase systems however, the propellants are poor solvents for most drugs. Cosolvents may be used.
Suspension preparations:
Are 3 phase systems and are harder to formulate and all the problems of suspensions (caking…) must be considered. Particle size of the solid must be considered as well as the use of surfactants as suspending agents.
- caking Agglomeration Particle growth Particle size Valve clogging Moisture content Solubility Surfactants Surfactants as suspending agents
Advantages of MDI’s (3)
- Portability, cost, disposability
- Many doses
- Protects drugs from oxidative degradation and microbiological
contamination
Disadvantages of MDI’s (3)
- Inefficient drug delivery (hitting the tongue)
- Incorrect use by patients
- Only 10-20% is delivered to the site of action even using correct
inhalation techniques.
Advantages and disadvantages of dry powder inhalers over MDI’s (7)
Advantages:
- Propellant free
- Breath actuated
- Can deliver larger drug doses
Disadvantages:
1. Limited by the patients ability to inhale
2. Increases the potential for inertial Impaction
3. Exposed to ambient atmospheric conditions (humidity may cause
powders to clump)
4. Less efficient at drug delivery than MDI’s
Describe the technological advances in powder production and formulation in improving inhalation drug delivery(powder aerosol delivery) of powders (7)
To improve inhalation drug delivery of powders
1. Powder production and formulation
A) Spray drying: converting atomised liquid droplets into dry
powders by hot air
B) Solvent precipitation: utilises properties of nonslovent
- Powder inhaler devices
A) Innovae: powered by a stored bolus of compressed air
B) SkyePharma:
C) Bead inhaler technology: use of beads to disperse the powders
on inhalation
D) Twisthaler: carries particles out of the device via a fluted
chimney, while larger particles a centrifuged into fine
particles.
E) Hovine flowcaps: capsule powder inhaler- pierced with 2 blades
What are the essential formulation requirements for nebuliser fluids (7)
- Are aqueous and may contain cosolvents and surfactants
- Iso-osmotic solutions pH >5
- Antioxidants and preseratives avoid where possible
- In general suspensions are poorly delivered from ultrasonic nebulisers
- First to be employed when investigating the delivery of new entities
- Ultrasonic nebulisers have not been successful for peptides or
liposomes - Shearing forces that occur in the nebuliser may produce time-
dependent damage to some materials.
Discuss temperature effects during nebulisation with a jet nebuliser (5)
- The aerosol output form a jet nebuliser undergoes a rapid decrease
in temperature of the liquid being nebulised by apprx 10-15degrees
Celsius
- some asthmatics experience bronchoconstriction on inhalation
of cold solutions
- cooling effects within the reservoir fluid reduces drug solubility
- increases surface tension and viscosity
- precipitation
What are the 3 principle methods employed in in vitro measurement / analysis of aerosol size (3)
- Microscopy
- Laser diffraction
- Cascade Impaction
