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Pharmacy Year 3 > Pulmonary Route of Administration > Flashcards

Pulmonary Route of Administration Flashcards

1
Q

Where are >5µm particles likely to deposit?

A

Upper airways

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2
Q

Where are 1-5µm particles likely to deposit?

A

Lower airways

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3
Q

Where are <1µm particles likely to deposit?

A

Pulmonary alveoli

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4
Q

What happens to 500nm particles?

A

Phagocytosis by alveolar macrophages

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5
Q

What is directly proportional to particle size?

A

Deposition by impaction and sedimentation

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6
Q

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

A

> 1µm

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7
Q

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

A

Small particles <1µm

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8
Q

When does impaction occur?

A

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

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9
Q

What is sedimentation by gravity related to?

A

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

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10
Q

By which mechanism do particle sizes <1m deposit?

A

Diffusional deposition. It is inversely related to particle size.

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11
Q

Inhalation is used as an alternative RoA if…

A
  • 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
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12
Q

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

A

Diameter
Density
Shape
Charge

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13
Q

What are the factors affecting particle deposition in liquid aerosols?

A

Velocity
Propellant
Particle size
Size distribution

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14
Q

Where are large particles more likely to be deposited?

A

In the upper airways

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15
Q

Define inertia

A

Property of a particle to resist changes in velocity

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16
Q

When does inertial impaction occur?

A

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

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17
Q

Do sub-micron particles have less or more inertia?

A

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

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18
Q

When is Brownian motion significant?

A

In the deposition of small particles affected b inertia and gravity

19
Q

What is the impact of electrostatic interaction?

A

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

20
Q

What are sprays useful for?

A

Targeting upper respiratory tract

21
Q

Do DPIs need a solvent propellant?

A

No - they dry powder fluidises when a patient inhales.

22
Q

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

A

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

23
Q

How does Optinose exhibit bidirectional flow?

A

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

24
Q

What can be used to enhance solubility in pMDIs?

A
  • Co-solvents e.g. ethanol
    It is a pressure modifier and enhances solubility of surfactant propellants
  • Inverse micelles / liposomes
25
Q

What can be used to improve wettability of pDMIs?

A

Surfactants - they finely divide active ingredients / excipients

26
Q

How can pMDI suspensions be stabilised?

A

Surface active agents (lecithin)

- they adsorb to particles and act as a steric barrier to agglomeration

27
Q

How can the valve be lubricated in pMDIs?

A

Surfactants / simple lubricating oi

- minimises friction

28
Q

What can be used to mask taste of pMDIs?

A

Menthol

29
Q

What is used as an anti-oxidant in pDMIs?

A

Ascorbic acid

30
Q

Give an example of a preservative used in pDMIs?

A

Benzalkonium chloride

31
Q

What kind of inhalers are needed for small airway disease?

A

Super fine particle inhalers

32
Q

What are the particle sizes used in SAD?

A

Ultrafine <100nm)

Extra fine <1µm

33
Q

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

A

Impaction and sedimentation

34
Q

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

A
  • show good efficacy
  • reduce daily dose of ICS
  • achieve greater asthma control
  • improved therapeutic window
35
Q

What are nebulisers used for?

A

Conditions where traditional inhalers would be inappropriate

To avoid banned and pressurised gases

36
Q

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

A

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

37
Q

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

A

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

38
Q

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

A

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

39
Q

What are the ideal particle properties for DPIs?

A

↓ size
↓ density
↑ shape factor

40
Q

How does hygroscopic growth affect aerosolisation and lung deposition?

A

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

41
Q

Which methods are used for micronisation?

A

Jet mill
Pin mill
Ball mill

42
Q

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

A

Solvent - lead to rapid expansion

Anti-solvents - solution enhanced dispersion

43
Q

How are excipients beneficial in DPI formulation?

A

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

44
Q

Why are excipients limited in DPI formulation?

A

The lung has low buffering capacity and can be easily irritated

Pharmacy Year 3 (11 decks)

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