Pulmonary drug delivery

Question 1

Define what the aerodynamic diameter of a particle is?

Answer 1

1. The diameter of a particle in the shape of a sphere that’s 1g/cm3
2. Measure of particle size and density
3. Works out how dense a particle is and how it affects the flight of the particle

Question 2

What are the mechanisms responsible for particulate deposition?

Answer 2

1. Impaction
2. Gravitational sedimentation
3. Diffusion

Question 3

Describe what gravitational sedimentation is and it depends on?

Answer 3

1. The settling of particles falling down due to gravity
2. Dependent on its size, density and the residence time on the airway
3. Important for small alveoli and small particles

Question 4

Describe what inertial impaction is and what it depends on?

Answer 4

1. The dominant deposition mechanism for particles that are more than 1 micrometer
2. Occurs in the upper tracheobronchial region
3. Large particles collide with airway walls
4. Responsible for larger particles

Question 5

Describe what the brownian diffusion is?

Answer 5

1. This is for particles below the size of 1 micrometer
2. Particles are bombarded by random molecules in the atmosphere- particles collide with the walls in the airways
3. Probability of particle deposition by diffusion
4. Increases as the particle size decreases

Question 6

How are particles deposited in various regions of the GI tract?

Answer 6

1. Upper part of the lung impacts on particles larger than 10 micrometers- rapidly removed by coughing, swallowing and mucocillary action
2. Smaller part of lung (alveoli) impact on particles 0.5 to 5 micrometers- deposit by impaction or sedimentation

Question 7

What are the physiological factors that affect particle deposition in the airways?

Answer 7

1. Lung morphology: particles must travel down series of tubes which cause it to decrease in size
2. Oral vs nasal breathing:
   - Nasal: majority of inhaled environmental particles are deposited in nose and pharynx
   - Pulmonary: aerosols via mouth
3. Inspiratory flow rate:
   - Increase means increase in deposition of particles by impaction
4. Breath Holding: (optimal method for aerosol)
   - After inhalation, holding your breath increases the chance of particles deposited by sedimentation and diffusion

Question 8

What are the five pharmaceutical factors which affect aerosol deposition?

Answer 8

1. Aerosol velocity: devices can alter this
2. Size to size distribution: small to large
3. Shape: not all particles are spherical
4. Density: denser particles may stick to other particles to form bigger ones
5. Physical stability

Question 9

Hows does the mucus barrier effect aerosolised powder and what factors depend on this?

Answer 9

1. Aerosolised powder needs to dissolve in the mucus layer to get into solution
2. It then diffuses pass the mucus layer onto the aqueous lining of epithelial liquid
3. Factors: Rate of diffusion relies on:
   - thickness mucus layer
   - mucus viscosity
   - molecular drug size
   - interactions between drug and mucus

Question 10

Hows does the mucocillary clearance effect aerosolised powder and what factors depend on this?

Answer 10

1. Mucus layer is constantly being propelled by the cilia in the lungs
2. Swallowed and digested in the stomach within 24 hours

Question 11

Give an example of a genetic disorder that may effect the mucocillary clearance in the lungs?

Answer 11

Cystic Fibrosis: overproduction of mucus

Question 12

Describe the advantages of pulmonary drug delivery for locally acting drugs?

Answer 12

1. Dose needed to produce pharmacological effect is reduced
2. Rapid onset of action: systemic circulation once absorbed
3. Avoids first pass metabolism as it avoids intestines and liver
4. Doesn’t cause gastrointestinal side effects, unless cilia doesn’t waft the drug
5. Lower concentrations = reduced systemic side effects

Question 13

Describe the advantages of pulmonary drug delivery for systemically acting drugs?

Answer 13

1. Large surface area for drug absorption
2. Works in an area with many blood vessels, fast onset of action
3. Permeability of compound is higher than small intestine or other mucosal routes
4. Less hostile environment than oral route so peptides and proteins are able to be administered this way

Question 14

Describe the disadvantages of pulmonary drug delivery for systemically acting drugs?

Answer 14

1. Complex devices are used to administer the drug which are complex to use
2. Aerosol devices are difficulty to follow and use which leads to patients having trouble absorbing the drug
3. Drug absorption may vary due to mucus
4. Retention time decreased by mucosal clearance

Question 15

What are the current technological methods for administering drugs via the pulmonary route?

Answer 15

1. Pressurised-Metered-Dose-Inhalers (pMDI)
2. Dry powder inhalers (DPI)
3. Nebulisers (masks)

Question 16

Describe how the pressurised metered dose inhalers work?

Answer 16

1. The most common form for pulmonary delivery
2. Drug is dissolved in liquid or suspended in liquid propellents (with surfactants)
3. Contained in a pressurised canister with a metering valve- sprays out predetermined dose
4. Volume expansion occurs in the passage and forms a mixture of gas and liquid
5. This high speed gas flow helps break up the liquid into little droplets

Question 17

What are the components that make up a pressurised metered dose inhaler?

Answer 17

1. Container (10 to 30mL) that’s chemically inert
2. Metering valve (designed to release fixed volume)
3. Elastomeric seal
4. Actuator

Question 18

Describe the properties of propellents?

Answer 18

1. Liquified gases that are usually CFCs or HFAs (low temperature)
2. Low pulmonary toxicity, highly stable and compatible with packaging materials
3. Most drugs insoluble in propellents and have to act in suspensions
4. CFCs are bad for the environment but this inhaler is convenient for use

Question 19

Describe the properties of a dry powder inhaler?

Answer 19

1. Drug is inhaled as a fine powder cloud of particles
2. Drug is either preloaded into the device or into a gelatine capsule that’s placed in the device
3. Easy to take the dose, have to inspire greatly and coughing reflex may occur

Question 20

Describe the properties of a multi-dose dry powder inhaler?

Answer 20

1. Drug is mixed with coarse lactose and filled into an aluminium foil blister disk
2. Loaded by the wheel and each contain 4 to 8 doses of drug

Question 21

Describe the properties of a nebuliser?

Answer 21

1. Converts micronised drugs or suspensions into aerosol inhalators
2. Deliver large volumes of drugs and used when the drug cannot form pressurised metered dose inhaler or DPI
3. It’s very heavy to carry around as it’s compressed gas

Question 22

Describe the method for aerosol analysis?

Answer 22

1. Radio-pharmaceuticals can directly measure it

2 Emolyed due size classification

3. Last diffracion
4. Cascade impaction