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PM2C Spring > Pulmonary Drug Delivery [Vitaliy] > Flashcards

Pulmonary Drug Delivery [Vitaliy] Flashcards

1
Q

What is pulmonary drug delivery?

A

Drug is delivered to the lungs to be absorbed into the blood circuulation

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2
Q

What occurs in the lungs?

A

The lung is an organ of external respiration

Oxygen and carbon dioxide are exchanged between blood and inhaled air

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3
Q

Why are the lungs an attractive drug target?

A

Large surface area

Good blood supply

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4
Q

What is the aerodynamic particle diameter (da)

A

The diameter of a sphere with a density of 1 g/cm3 that has the same aerodynamic behaviour as the particle which shall be characterised

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5
Q

List the 3 processes responsible for particulate deposition in the lungs

A
  1. Impaction
  2. Gravitational sedimentation
  3. Diffusion

Different particles will deposit differently in the lungs

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6
Q

What is gravitational sedimentation?

A

Particles settling under gravity will attain a constant terminal settling velocity, Vt
Gravitational sedimentation of an inhaled particle is dependent on its size, density and residence time in the airways

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7
Q

What is inertial impaction?

A

This is the dominant deposition mechanism for particles > 1um in the upper tracheobronchial regions
A particle with a large momentum may be unable to follow the changing direction of the inspired air as it passes the bifurcations - so it will collide with the airway walls

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8
Q

What is brownian diffusion?

A

Of little significance for particles > 1um
Particles below this size are displaced by a random bombardment of gas molecules = particle collision in the airways
The probability of particle deposition by diffusion increases as the particle size decreases

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9
Q

How are larger particles (greater then 10um) deposited in the airways?

A

The particles will impact in the upper airways

They are rapidly removed by coughing, swallowing and mucociliary processes

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10
Q

How are smaller particles (0.5-5um) deposited in the airways?

A

The particles may escape impaction in the upper airways and will deposit by impaction and sedimentation in the lower airways

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11
Q

Describe the structure of the airways

A

Trachea > Mainstream bronchus > Lobar bronchus > (Segmental bronchus) > Bronchiole > Aveolar duct > Aveolus

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12
Q

List the 4 physical factors which affect particle deposition in the airways

A
  1. Lung morphology = drug particles must pass down a successive series of branching tubes of constantly decreasing size
  2. Oral vs nasal breathing = for pulmonary, aerosols are inhaled via the mouth
  3. Inspiratory rate flow = increasing inspiratory rate flow will enhance deposition by impaction in the larger airways
  4. Breath holding = enhances the deposition of particles by sedimentation and diffusion
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13
Q

How does optimal aerosol deposition occur?

A

With slow, deep inhalations to total lung capacity

Followed by breath-holding prior to exhalation

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14
Q

List 5 pharmaceutical factors affecting aerosol deposition

A
  1. Aerosol velocity
  2. Size and size distribution
  3. Shape
  4. Density
  5. Physical stability
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15
Q

Describe the journey of the drug particles through the mucus barrier

A

The drug needs to dissolve in the mucus layer
Once in solution, the drug will then diffuse through the mucus layer and enter the aqueous environment of the epithelial lining liquid

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16
Q

What will the rate of diffusion through the mucus layer depend on?

A

Mucus viscosity
Molecular size of drug
Interactions between drug and mucus

17
Q

What is mucociliary clearance?

A

The mucus layer does not exist as a stagnant layer - constantly propelled along the airways by rhythmic beating of the cilia on epithelial cells

18
Q

List 3 advantages of pulmonary drugs delivery for locally-acting drugs

A
  1. Reduced dose compared to oral dosing
  2. rapid onset of action
  3. Reduced side effects as reduced dose
19
Q

List 2 advantages of pulmonary drug delivery for systemically acting drugs

A
  1. Large surface area for drug absorption

2. Highly vascular surface promotes rapid absorption and onset of action

20
Q

List 2 disadvantages of delivery of systematically-acting drugs via the pulmonary route

A
  1. Complex delivery delivery devices are required to target drugs to the airways - may be inefficient
  2. Drug absorption may be limited because of mucus
21
Q

What are the 3 current devices use to delivery drugs to the lungs?

A
  1. Pressurised metered-dose (pMDI)
  2. Dry powder inhalers (DPI)
  3. Nebulisers
22
Q

Explain how a pressurised metered-dose inhaler (pMDI) works

A

The most commonly used inhalation drug delivery system

  1. Drug is either dissolved or suspended in a liquid propellant with other excipients
  2. It is preserved in a pressurised canister and fitted with a metering valve
  3. A predetermined dose is released as a spray on actuation on the metering valve
  4. When released from the canister, it undergoes volume expansion and forms a mixture of gas and liquid
  5. The high speed gas flow helps to break up the liquid into a fine spray of droplets
23
Q

What components make up a pMDI?

A

Container - chemically inert
Metering valve - designed to release fixed volume
An elastomeric seal
The actuator

24
Q

What are propellants?

A

Usually liquefied gases

Traditionally these are CFCs and increasingly hydrofluoroalkanes (HFAs)

25
Q

List 3 criteria of propellants used in pMDIs

A
  1. Low pulmonary toxicity
  2. High chemical stability
  3. Compatibility with packaging

Most of the drugs are insoluble in the propellants, they are usually presented in suspensions

26
Q

How does a dry powder inhaler work (DPI)?

A
  • The drug is inhaled as a cloud of fine particles
  • The drug is either preloaded in the device or filled into hard gelatin capsules/foil blister discs which are loaded into the device prior to use
27
Q

How do multi-dose DPIs work?

A

The drug is mixed with a coarse lactose carrier and filled into an aluminium foil blister disk
The patient loads this into the device on a support wheel
Each disc contains 4 or 8 doses of drug

28
Q

How do nebulisers work?

A
  • Nebulisers convert aqueous solutions or micronised suspensions of drug into an aerosol for inhalation
  • They deliver relatively large volumes of drug solutions/suspensions
  • Frequently used where the therapeutic dose is too large for delivery with the inhalers
29
Q

How can the regional distribution of aerosols in the airways be measured?

A

Using radiopharmaceuticals

30
Q

How can the aerosol size by analysed?

A
  1. Microscopy
  2. Laser diffraction
  3. Cascade impaction

PM2C Spring (6 decks)

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