Aerosols

Question 1

Aerosizer

Answer 1

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

Question 2

What is Aerodynamic diameter?

Answer 2

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

Question 3

What are the advantages of local action?

Answer 3

Direct access to site of disease

Rapid onset of action

Avoid GI tract + first-pass metabolism

Lower doses

Fewer side effects

Question 4

Next generation impactor

Answer 4

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

Question 5

Andersen cascade impactor

Answer 5

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

Question 6

Aerodynamic diameter equation

Answer 6

daer = dsqroot( p / p1) - p1 = 1g/cm3

Question 7

Impaction methods

Answer 7

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

Question 8

Electron microscopy

Answer 8

Microscopy gives shape & texture data as well as size Diff. Equivalent diameters can be constructed around same particle

Question 9

How do we calculate settling velocity?

Answer 9

Calculated by Stoke’s law

Question 10

What is Sedimentation?

Answer 10

Particles settle by gravitation onto the airway walls

Most important in smaller airways + alveoli, and horizontally-oriented airways

Settling velocity proportional to diameter

Question 11

How do we clear deposited particles in the upper airway epithelium?

Answer 11

Its covered with mucus

Mucociliary escalator: ciliary action moves mucus towards pharynx where swallowed by GI Tract

Clearance within hours

Question 12

Multistage liquid impinger

Answer 12

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

Question 13

Light diffraction

Answer 13

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

Question 14

Principle of operation in impaction methods

Answer 14

Impactors - stages arranged in a stack Connect to vacuum pump

Question 15

What is Brownian diffusion?

Answer 15

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)

Question 16

How do we clear deposited particles in the alveolar region?

Answer 16

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

Question 17

Electrostatic deposition

Answer 17

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

Question 18

What are the advantages of systemic action”?

Answer 18

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)

Question 19

What is Microscopy?

Answer 19

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

Question 20

What are the 5 main mechanisms for particles to deposit within respiratory tract?

Answer 20

SIIDE

Inertial impaction

Sedimentation

Diffusion

Interception

Electrostatic precipitation

When particles contact airway walls, they do not return back to airflow

Question 21

How do we deliver drugs into the airways (pulmonary)?

Answer 21

Drugs delivered in the form of an aerosol

Suspension of liquid/solid particles in a gas

Sufficiently small to remain airborne for considerable time

Question 22

Twin liquid impinger

Answer 22

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

Question 23

Why deliver drugs to the lung?

Answer 23

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

Question 24

Apparatus for impaction methods

Answer 24

Twin stage liquid impinger Andersen cascade impactor Multistage liquid impinger Next generation impactor

Question 25

What is the purpose of airways?

Answer 25

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

Question 26

What is Inertial impaction?

Answer 26

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

Question 27

What is Interception?

Answer 27

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.

Question 28

How can we measure particle size of inhaled products?

Answer 28

Microscopy

Laser diffraction

Aerosizer

Question 29

What is Respirable fraction?

Answer 29

% 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