Systemic drug delivery through the lung

Systemic drug delivery through the lung

Sufficient drug must be deposited in the alveolar cavity, so that adequate amount of a drug would be absorbed into the systemic circulation to elicit therapeutic efficacy. Aerosolized systems present the drug in a particulate form with an intensity of airflow, which may allow the drug to pass through the lung architecture and reach the alveoli. However, traditional inhalation devices deposited only ~10%–15% of the inhaled drug in the lung.

Certain design elements of the DDS that can permit systemic drug absorption through the lung include the following:

1. Size and drug loading of the particles: Fine aerosols deposit better in the lung alveoli and peripheral airways but have a lower amount of a drug per unit surface area. The relatively coarse aerosol particles deposit more drugs per unit surface area, but tend to be deposited in the cen-tral, larger pathways that are subject to mucosal clearance, low surface area, and poor drug absorption. For example, particles with a diameter in the range of ~60 μm tend to deposit in the trachea, whereas particles in the size range of ~2 μm tend to deposit in the alveoli. Aerodynamic diameter and size distribution of the particles need to be carefully con-trolled to maximize particle deposition in the alveoli.

2. Density of the particles: Particle density contributes to the inertia of the particle. In addition, being inversely related to particle porosity, particle density also impacts diffusivity of the drug through the par-ticle at the site of absorption.

3. Particle shape: Ideal particle shape for pulmonary drug delivery is spherical. However, pharmaceutical formulations tend to have an irregular shape, whereas crystalline drugs may have markedly high aspect ratio (ratio of length to width) of their particles. Deviation from sphericity can reduce the alveolar deposition of a drug.

4. Aggregation: Particle surface charge and other surface characteris-tics that may promote particle adhesion can increase the size of the agglomerates in the respiratory tract, thus compromising the propor-tion of the formulation from reaching the alveoli.

5. Hygroscopicity: Since the respiratory tract presents a high humidity local environment, particles that are hygroscopic and may change their sur-face adhesion or size characteristics rapidly on exposure to a high humid-ity environment may not achieve optimal particle deposition in the lung.