Drug delivery to the respiratory tract

Question 1

Lung function

Answer 1

• cells in the bronchioles have cilia
• mucous is secreted forming a thin protective layer over the bronchioles
• cilia beat rhythmically to push mucous upwards towards pharynx where it is swallowed

Inhaled particles either :
- dissolve in the lower lung regions
- are removed by mucous

Question 2

Particle Deposition

Answer 2

• for effective treatment, aerosol particles must reach the smaller airways for local or systemic absorption
• Particles larger than 10 micrometres are deposited in the back of the mouth and throat
• particles between 5-10 micrometres are deposited in the central airways
• particles less than 5 micrometres are deposited in the peripheral airways ideal for pulmonary absorption

Question 3

Mechanisms of lung deposition

Answer 3

• Inertial impaction = particle size greater than 5 micrometres
• Sedimentation = particle size between 1-8 micrometres
• Diffusion = particle size less than 1 micrometre in diameter

Question 4

Inertial impaction

Answer 4

• particles have inertia which means they move in a straight line unless something forces them to change direction
• the likelihood of particles impacting a surface or continuing with the airflow depends on two factors ; mass and velocity.

Heavier and faster moving particles have more inertia making them more likely to impact surfaces.

Question 5

Sedimentation

Answer 5

Occurs for smaller particles that are able to follow the airstream and penetrate the more peripheral bronchioles and alveoli. Here the airstream flows slower allowing the particles to settle on to the airway surfaces either during the course of slow steady breathing or during breath holding.

Particles fall under gravity and larger particles sediment faster. After inhalation, a patient should hold his breath to allow time for sedimentation

Question 6

Diffusion

Answer 6

Process by which particles deposit due to random movement known as Brownian motion.

Diffusion predominates for very small particles.

This mechanism mainly occurs in the periphery pf the lung, particularly in the bronchioles and alveoli. Only a small number of particles deposit through diffusion, making it of negligible importance for most therapeutic aerosis

Question 7

Human factors affecting particle deposition in airways

Answer 7

• airway caliber = refers to size and openness of the airways which can be affected by lung anatomy
• breathing patterns = speed at which a patient inhales impacts airflows and how particles behave. Faster airflow means more impaction while slower airflow allows for sedimentation
• patient coordination = refers to the ability of a patient to correctly time their inhalation

Question 8

Technical factors affecting particle deposition in airways

Answer 8

• particle size = larger particles more likely to deposit via impaction while smaller by sedimentation or diffusion. The most important size range for pulmonary deposition is 1-5 micrometres.
• particle shape = aerodynamic of particles are affected by their shape
• inhaler design = efficiency depends on how well the inhaler is designed to generate the correct particle size and ensure proper dispersion of the aerosol

Question 9

Pressurized metred dose inhalers VS dry powder inhalers

Answer 9

PMDIs = particles are expelled at high speed die to the pressure inside the inhaler. Patients are advised to breathe in slowly to ensure proper deposition of particles

DPIs = a fast inhalation is needed because there is no internal pressure so fast inhalation helps disaggregate the powder into small particles that can be carried into the lungs

if particles are too small, they may be exhaled without depositing.

Question 10

Receptor distribution variations

Answer 10

• Salbutamol ( B2 AGONIST) - most B2 agonists are concentrated in the small airways and alveolar walls. To be effective, salbutamol needs to be delivered more peripherally focusing on medium and small airways

Ipratropium bromide (M3 AGONIST) - M3 RECEPTORS are primarily located in smooth muscles, submucosal glands and airway ganglia. For therapeutic benefit, ipratropium should be targeted at the conducting airways.

Anti-inflammatory drugs = these drugs like inhaled steroids , need to be evenly distributed throughout the lungs because inflammatory cells are found in both the airways and alveolar tissues

Question 11

Chemical nature of the particles

Answer 11

• HYDROPHILICITY OF PARTICLES = the air in the lungs airways is highly humid with 99% relative humidity. If the active drug is attracted to water, water condenses on the surface of drug particles. this leads to particle growth as the particles absorb water while travelling through the airways

Hygroscopicity of the particles = refers to the ability to absorb moisture from the air. Higher deposition occurs in the upper respiratory tract that might have been expected because of the moisture absorption. This can result in a loss of efficacy if the drug deposits in the wrong area. To improve deposition, we can coat hydrophilic particles with a hydrophobic substances to reduce moisture absorption.