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.
Advantages
Large Surface Area: The alveoli provide an extensive absorption site.
Rapid Absorption: Thin epithelial barriers and vascularization facilitate swift drug uptake.
Bypassing First-Pass Metabolism: Drugs directly enter systemic circulation.
Non-invasiveness: Inhalation improves patient compliance over injectables.
Disadvantages
Deposition Variability: Inefficient deposition may limit drug reaching the lungs.
Technique Dependency: Incorrect inhalation affects drug delivery efficiency.
Stability Issues: Some drugs are unstable in inhalation formulations.
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.
