L15 - Lungs drug delivery

Question 1

What is the mucocililary clearance mechanism?

Answer 1

• Cilia (formed from ciliated epithelial cells lining the trachea and bronchi) move the mucus gel layer (secreted from goblet cells) with entrapped foreign particles upwards towards the pharynx where expectoration (spitting out) or swallowing the mucus to the stomach occurs.

Question 2

What is the phase of an aerosol?

Answer 2

Solid or liquid particles dispersed in a gaseous phase.

Question 3

When is pulmonary administration of drugs needed?

Answer 3

• Localised disorders— asthma, COPD, infections
• Systemic delivery of drugs
  Why? :
• high surface area
• well perfused tissues
• avoids first pass metabolism

Question 4

Factors affecting pulmonary drug delivery

Answer 4

• Physicochemical properties of drug:
• particle size/distribution
• surface topography (roughness)
• Formulation design:
• excipients
• impact on aerosol properties
• Delivery device:
• pressurised metered dose inhaler (pMDI)
• dry powdered inhaler (DPI)
• nebuliser
• Patient factors:
• age
• physical condition
• cognitive ability
• preference

Question 5

Effect of particle size on aerosols

Answer 5

• Decrease in diameter from bronchi to bronchioles near alveoli — aerosol particle size is important factor where it is deposited
• Particle size - referred as aerodynamic diameter, d(a)

Question 6

Equation for aerodynamic diameter [d(a)]

Answer 6

d(a) = ( p / p0 )^0.5 x d(p)

d(a) = aerodynamic diameter
d(p) = diameter of particle under examination
p = density of particle under examination
p0 = density of spherical particle (1g/cm3)

• Density depends on porosity of the particle which can be manipulated by:
• choice of excipients
• formulation processing during manufacture
• Porous particles will have a smaller apparent aerodynamic diameter
• E.g. calculation used for dry powder inhaler material – manufactured using spray drying technique

Question 7

Mass Median Aerodynamic Diameter (MMAD)

Answer 7

• MMAD = average particle size
• If MMAD > 5mcm (micrometer) ==> particles deposited in upper airways (impaction)
• If MMAD = 2-5mcm ==> particles deposited within bronchioles and alveoli (sedimentation)
• If MMAD < mcm ==> particles reach alveolar but are exhaled again (Brownian diffusion)

Question 8

Effect of airway humidity

Answer 8

• At high humidity inside lungs - interaction with aerosol particle which changes the resultant aerodynamics of the aerosol
• No effect on hydrophobic surface of aerosol, e.g. glucocorticoid particle in beclometasone
• Effect shown with hydrophilic surface, e.g. DPI lactose particle

Question 9

What are the options for Nicotine Replacement Therapy (NRT)?

Answer 9

• Patches
• Chewing gums
• Sprays (nasal & oromucosal)
• Inhalator