The aim of this in silico study was to investigate the effect of particle size, flow rate, and tidal volume on drug targeting to small airways in patients with mild COPD. Design of Experiments (DoE) was used with an in silico whole lung particle deposition model for bolus administration to investigate whether controlling inhalation can improve drug delivery to the small conducting airways. The range of particle aerodynamic diameters studied was 0.4 - 10µm for flow rates between 100 - 2000mL/s (i.e., low to very high), and tidal volumes between 40 - 1500mL. The model accurately predicted the relationship between independent variables and lung deposition, as confirmed by comparison with published experimental data. It was found that large particles (~ 5µm) require very low flow rate (~ 100mL/s) and very small tidal volume (~ 110mL) to target small conducting airways, whereas fine particles (~ 2µm) achieve drug targeting in the region at a relatively higher flow rate (~ 500mL/s) and similar tidal volume (~ 110mL). The simulation results indicated that controlling tidal volume and flow rate can achieve targeted delivery to the small airways (i.e., > 50% of emitted dose was predicted to deposit in the small airways), and the optimal parameters depend on the particle size. It is hoped that this finding could provide a means of improving drug targeting to the small conducting airways and improve prognosis in COPD management.