Introduction to Pulmonary Routes of Drug Delivery

• The pulmonary route delivers drugs via inhalation into the lungs, traditionally for respiratory diseases like asthma and COPD. However, its potential extends to systemic drug delivery and vaccination.

• The lungs' large surface area (~100 m² in adults), thin epithelial lining, and rich microvasculature enable rapid absorption and systemic delivery.

Pulmonary Routes of Drug Delivery

Advantages

1. Large Surface Area: The alveoli provide an extensive absorption site.

2. Rapid Absorption: Thin epithelial barriers and vascularization facilitate swift drug uptake.

3. Bypassing First-Pass Metabolism: Drugs directly enter systemic circulation.

4. Non-invasiveness: Inhalation improves patient compliance over injectables.

Disadvantages

1. Deposition Variability: Inefficient deposition may limit drug reaching the lungs.

2. Technique Dependency: Incorrect inhalation affects drug delivery efficiency.

3. Stability Issues: Some drugs are unstable in inhalation formulations.

4. Potential Respiratory Irritation: Certain formulations may irritate the airways.

Mechanisms of Respiratory Deposition

• The deposition of drug particles in the lungs depends on their size, airflow, and physiological factors:

Inertial Impaction:

• Affects larger particles (>5 µm).

• Predominantly occurs in upper airways and bifurcations.

Sedimentation (Gravitational Settling):

• Affects particles 1-5 µm.

• Predominant in bronchioles and alveoli, especially with breath-holding.

Brownian Diffusion:

• Relevant for ultrafine particles (<1 µm).

• Random motion due to interaction with gas molecules results in deposition in the alveoli.

Electrostatic Precipitation:

• Particles with electrostatic charges may be influenced by oppositely charged airway surfaces.

Factors Influencing Pulmonary Drug Absorption

Particle Size:

• 1-5 µm: Optimal for deep lung deposition.

• Larger particles deposit in upper airways, while smaller particles may be exhaled.

Breathing Pattern:

• Deep, slow inhalation followed by breath-holding improves alveolar deposition.

Airway Conditions:

• Diseases like asthma or COPD alter geometry and mucus properties, affecting drug deposition.

Formulation Properties:

• Excipients, pH, and drug stability influence solubility, absorption, and delivery.

Device Type:

• Metered-Dose Inhaler (MDI): Requires proper coordination for effective delivery.

• Dry Powder Inhaler (DPI): Suitable for patients with sufficient inhalation force.

• Nebulizer: Ideal for patients unable to use MDIs or DPIs.

Mucociliary Clearance:

• Cilia in the bronchial region transport mucus and entrapped particles toward the throat, reducing absorption time.

Applications of Pulmonary Routes of Drug Delivery

• Respiratory Treatments: Asthma, COPD, cystic fibrosis.

• Systemic Therapies: Insulin, analgesics.

• Vaccination: Inhaled vaccines for respiratory or systemic immunity.

• CNS Delivery: For neurodegenerative diseases via nose-to-lung-to-brain pathways.

The pulmonary route represents a versatile and effective means of drug delivery, offering rapid, non-invasive, and systemic therapeutic benefits.