Pulmonary Route of Administration

Question 1

Where are >5µm particles likely to deposit?

Answer 1

Upper airways

Question 2

Where are 1-5µm particles likely to deposit?

Answer 2

Lower airways

Question 3

Where are <1µm particles likely to deposit?

Answer 3

Pulmonary alveoli

Question 4

What happens to 500nm particles?

Answer 4

Phagocytosis by alveolar macrophages

Question 5

What is directly proportional to particle size?

Answer 5

Deposition by impaction and sedimentation

Question 6

Which particle size is deposition by impaction and sedimentation most effective for?

Answer 6

> 1µm

Question 7

Which particle size is deposition by impaction and sedimentation least effective for?

Answer 7

Small particles <1µm

Question 8

When does impaction occur?

Answer 8

When a particle with sufficient momentum doesn’t change direction with airflow in a curved airway and impacts on the wall.

Question 9

What is sedimentation by gravity related to?

Answer 9

Residence time in an airway and its terminal settling velocity, it is increased by holding breath.

Question 10

By which mechanism do particle sizes <1m deposit?

Answer 10

Diffusional deposition. It is inversely related to particle size.

Question 11

Inhalation is used as an alternative RoA if…

Answer 11

• there is chemical or physical interaction with other concurrent medicine
• a drug exhibits variable / erratic pharmacokinetics upon oral administration
• there is breakdown in GI tract

Question 12

What are the factors affecting particle deposition in dry powder products?

Answer 12

Diameter
Density
Shape
Charge

Question 13

What are the factors affecting particle deposition in liquid aerosols?

Answer 13

Velocity
Propellant
Particle size
Size distribution

Question 14

Where are large particles more likely to be deposited?

Answer 14

In the upper airways

Question 15

Define inertia

Answer 15

Property of a particle to resist changes in velocity

Question 16

When does inertial impaction occur?

Answer 16

When particle inertia / momentum makes a particle unable to change direction with flow

Question 17

Do sub-micron particles have less or more inertia?

Answer 17

They have less - they are less likely to impact in the upper or lower airways

Question 18

When is Brownian motion significant?

Answer 18

In the deposition of small particles affected b inertia and gravity

Question 19

What is the impact of electrostatic interaction?

Answer 19

Charge on particles induces the opposite charge on the lung wall and accelerates particles in its proximity

Question 20

What are sprays useful for?

Answer 20

Targeting upper respiratory tract

Question 21

Do DPIs need a solvent propellant?

Answer 21

No - they dry powder fluidises when a patient inhales.

Question 22

Where is a drug deposited in the upper airway likely to be absorbed?

Answer 22

GI tract - cilia move particles to the throat where they are swallowed so they can be absorbed in the GI

Question 23

How does Optinose exhibit bidirectional flow?

Answer 23

Uses the connecting pathway opening between nostrils for a dose to enter by one nostril and leave by the other nostril, this allowed small particles to penetrate to the true nasal mucosa at the back of the nose

Question 24

What can be used to enhance solubility in pMDIs?

Answer 24

• Co-solvents e.g. ethanol
  It is a pressure modifier and enhances solubility of surfactant propellants
• Inverse micelles / liposomes

Question 25

What can be used to improve wettability of pDMIs?

Answer 25

Surfactants - they finely divide active ingredients / excipients

Question 26

How can pMDI suspensions be stabilised?

Answer 26

Surface active agents (lecithin) | - they adsorb to particles and act as a steric barrier to agglomeration

Question 27

How can the valve be lubricated in pMDIs?

Answer 27

Surfactants / simple lubricating oi | - minimises friction

Question 28

What can be used to mask taste of pMDIs?

Answer 28

Menthol

Question 29

What is used as an anti-oxidant in pDMIs?

Answer 29

Ascorbic acid

Question 30

Give an example of a preservative used in pDMIs?

Answer 30

Benzalkonium chloride

Question 31

What kind of inhalers are needed for small airway disease?

Answer 31

Super fine particle inhalers

Question 32

What are the particle sizes used in SAD?

Answer 32

Ultrafine <100nm) | Extra fine <1µm

Question 33

What 2 factors contribute to most of a dose not being deposited in the lung?

Answer 33

Impaction and sedimentation

Question 34

What are the benefits of using smaller particles in disease states?

Answer 34

- show good efficacy - reduce daily dose of ICS - achieve greater asthma control - improved therapeutic window

Question 35

What are nebulisers used for?

Answer 35

Conditions where traditional inhalers would be inappropriate To avoid banned and pressurised gases

Question 36

Describe the process by which an air jet nebuliser releases the drug

Answer 36

Compressed air/oxygen exits a narrow office at high velocity When are is forced through, negative pressure at the exit draws up liquid from a tube Liquid is drawn up in fragments into an aerosol with droplet sizes >40µm Larger particles are removed, a bend allows them to impact and return to a reservoir

Question 37

Describe the process by which an air ultrasonic nebuliser releases the drug

Answer 37

There is no need for compressed gas Aerosol is created using Piezoelectric crystals Piezoelectric transducers vibrating at 1-3MHz are shaped to focus ultrasound waves within the liquid Intense agitation at focus - conical fountain above liquid - dispersed to create an aerosol Larger aerosol particles are removed by impaction

Question 38

Describe the process by which a vibrating mesh ultrasonic nebuliser releases the drug

Answer 38

By process of Piezo crystals expanding and contracting, this is driven by alternating voltage, the mesh is pulled back into the liquid and then thrown forward Near mono-disperse fine droplets are ejected with every forward thrust of the mesh Almost all the liquid is converted to an aerosol for inhalation

Question 39

What are the ideal particle properties for DPIs?

Answer 39

↓ size ↓ density ↑ shape factor

Question 40

How does hygroscopic growth affect aerosolisation and lung deposition?

Answer 40

Leads to irreversible aggregation, altered adhesive and cohesive properties and increase in particle size

Question 41

Which methods are used for micronisation?

Answer 41

Jet mill Pin mill Ball mill

Question 42

How does super-critical fluid particle engineering micronise DPI active ingredients?

Answer 42

Solvent - lead to rapid expansion | Anti-solvents - solution enhanced dispersion

Question 43

How are excipients beneficial in DPI formulation?

Answer 43

Improve dispensing Improve metering Reduce cohesion by occupying high energy sites of micronised particles

Question 44

Why are excipients limited in DPI formulation?

Answer 44

The lung has low buffering capacity and can be easily irritated