Aerosols Flashcards
Aerosizer
Measures particles one at a time in the range of 0.20 to 700 microns between 2 laser beams - dry powder / sprayed from a liquid suspension - measures aerodynamic diameter
What is Aerodynamic diameter?
Diameter of a ‘pretend’ sphere with a density of 1g/cm3 that has the same settling velocity in air as particle of interest
Governs deposition by sedimentation + inertial impaction
Determines site of particle deposition in lungs
Particles with different sizes have same aerodynamic diameter - they have diff. overall densities
What are the advantages of local action?
Direct access to site of disease
Rapid onset of action
Avoid GI tract + first-pass metabolism
Lower doses
Fewer side effects
Next generation impactor
7 stages Calibrated to flow rate required powder collected in cups - minimal particle bounce Size distribution Combines advantage of both cascade impacter + multi-stage liquid impinger
Andersen cascade impactor
8 stages Calibrated for a flow rate of 28.3 L/min Add oil to the sides so that particle don’t bounce off the metL Cut offs calculated according to flow rate Powder collected on dry stages Size distribution Labour intensive
Aerodynamic diameter equation
daer = dsqroot( p / p1) - p1 = 1g/cm3
Impaction methods
Another way of measuring particle size Use of artificial lung Measure aerodynamic diameter of particles Predicts site of deposition Operate on the principle of inertial impaction
Electron microscopy
Microscopy gives shape & texture data as well as size Diff. Equivalent diameters can be constructed around same particle
How do we calculate settling velocity?
Calculated by Stoke’s law
What is Sedimentation?
Particles settle by gravitation onto the airway walls
Most important in smaller airways + alveoli, and horizontally-oriented airways
Settling velocity proportional to diameter
How do we clear deposited particles in the upper airway epithelium?
Its covered with mucus
Mucociliary escalator: ciliary action moves mucus towards pharynx where swallowed by GI Tract
Clearance within hours
Multistage liquid impinger
4 stages Calibrated to flow rate required Powder collected in solvent @ each stage - minimal particle bounce & re-entrainment More complex than twin but less than cascade
Light diffraction
Small particles diffract light through large angle Large particles diffraction light through a small angle Detector measures light pattern produced Computer calculated particle size distribution (quick & simple) Assumes spherical particle
Principle of operation in impaction methods
Impactors - stages arranged in a stack Connect to vacuum pump
What is Brownian diffusion?
Small particles leave their original flow lines by diffusion + deposit onto airway walls
For particles < 0.5 micrometres
For smaller airways (short distance, long residence time)
How do we clear deposited particles in the alveolar region?
There is no mucus, no cilia
Insoluble particles cleared very slowly (years, months)
Clearance of soluble particles: dissolve + enter bloodstream
Clearance of insoluble particles by macrophages (phagocytosis) or surface tension effects
Electrostatic deposition
Charged particles are attracted towards the airway walls by the electrostatic charges
Aerosols with high charge and concentration can repel each other and drive particles towards the airway walls.
Normally not important. Only for freshly generated (and charged) aerosols, for instance from nebulisers
What are the advantages of systemic action”?
Avoid GI Tract
Avoids first-pass metabolism
Non- invasive, needle free
High bioavailability compared to other invasive routes
Rapid absorption, rapid onset of action (insulin, opioids)
What is Microscopy?
2 types:
- optical (0.5 - 1000micrometre)
- electron (1nm - 5um)
Several equivalent diameters
- ferets, martins
Methods of size measurement
- automatic image analysis
- expensive but popular
- quantify shape data
What are the 5 main mechanisms for particles to deposit within respiratory tract?
SIIDE
Inertial impaction
Sedimentation
Diffusion
Interception
Electrostatic precipitation
When particles contact airway walls, they do not return back to airflow
How do we deliver drugs into the airways (pulmonary)?
Drugs delivered in the form of an aerosol
Suspension of liquid/solid particles in a gas
Sufficiently small to remain airborne for considerable time
Twin liquid impinger
2 stage Powder pulled from inhaler by vacuum pump Large particles settle @ upper chamber Small particles @ lower chamber Cheap + easy No size distribution Powder collected in solvent
Why deliver drugs to the lung?
Deliver to bring about a:
- local effect (bronchodilators, corticosteroids, antibiotics, muscolytics)
- systemic effect (peptide drugs - insulin, anaesthetics - halothane)
rapid onset of action
smaller doses than oral formulations
less systemic and GI adverse effects
comfortable
Apparatus for impaction methods
Twin stage liquid impinger Andersen cascade impactor Multistage liquid impinger Next generation impactor
What is the purpose of airways?
Heat + humidity inhaled air (conditioning)
Remove particles from inhaled air by deposition (filter)
Clear away the deposited particles efficiently into GI Tract
Particles should not reach alveoli where gas exchanges
Particles > 10 microns do not reach alveoli
What is Inertial impaction?
Air flows easily around bends
Particles in the air leave this flow due to their inertia and may impact airway walls
Heavier the particle, the more inertia (resistance to change velocity - speed)
Huge particles deposit quickly in the upper airways
What is Interception?
Without deviating from their original flow lines, particles contact the airway surface because of their physical size/shape
Long fibres can be easily intercepted: Small aerodynamic particle diameter, large in one dimension.
How can we measure particle size of inhaled products?
Microscopy
Laser diffraction
Aerosizer
What is Respirable fraction?
% of drug present in aerosol particles less than 5 microns in size + likely to be deposited
Determines by particle sizing techniques or use of device which simulate inhalation process such as:
- Anderson cascade impacted
- Next generation impinger
