Modelling Drug Delivery to the Small Airways: Optimization Using Response Surface Methodology.

Area of Science:

• Pulmonary Drug Delivery
• Computational Fluid Dynamics
• Respiratory Medicine

Background:

• Chronic Obstructive Pulmonary Disease (COPD) management relies on effective inhaled drug delivery.
• Targeting small airways in COPD is crucial for optimal therapeutic outcomes.
• Current inhalation strategies may not efficiently deliver medication to the peripheral lung regions.

Purpose of the Study:

• To investigate the impact of particle size, flow rate, and tidal volume on drug deposition in small airways.
• To determine optimal inhalation parameters for enhanced drug targeting in mild COPD.
• To utilize an in silico model for simulating drug delivery dynamics.

Main Methods:

• Employed a Design of Experiments (DoE) approach with an in silico whole lung particle deposition model.
• Simulated bolus administration across a range of particle sizes (0.4-10 µm).
• Investigated varying flow rates (100-2000 mL/s) and tidal volumes (40-1500 mL).

Main Results:

• Model validation confirmed accurate prediction of lung deposition based on experimental data.
• Large particles (~5 µm) require low flow rate (~100 mL/s) and small tidal volume (~110 mL) for small airway targeting.
• Fine particles (~2 µm) can target small airways at higher flow rates (~500 mL/s) with similar tidal volumes (~110 mL).

Conclusions:

• Controlling tidal volume and flow rate enables targeted drug delivery to small airways (>50% emitted dose).
• Optimal inhalation parameters are particle-size dependent.
• Findings offer a strategy to improve COPD treatment efficacy through enhanced small airway drug targeting.