Novel system to investigate the effects of inhaled volume and rates of rise in simulated inspiratory air flow on fine particle output from a dry powder inhaler

摘要

This study evaluated the effect of inhaled volume and simulated inspiratory flow rate ramps on fine particle output from dry powder inhalers (DPIs). A simple, robust system was developed to account for “rate of rise” (ramp) effects while maintaining a constant air flow through a multi-stage liquid impinger (MSLI), used for sizing the emitted particles. Ramps were programmed to reach 30 and 60 L/min over 100 milliseconds; 500 milliseconds; and 1, 2, and 3 seconds. Rotahaler was chosen as the test DPI. Testing was done with simulated inhalation volumes of 2 L and 4 L. Testing was also carried out using the USP apparatus 4. At 30 L/min, for a 2 L volume, the amount of drug exiting the device in fine particle fraction (FPF) increased from 2.33 μg to 6.04 μg from the 3-second ramp to the 100-millisecond ramp, with 11.64 μg in FPF for the USP (no ramp) method. At the same flow rate, for a 4 L volume, FPF increased from 2.23 μg to 8.45 μg, with 10.25 μg for the USP method. At 60 L/min, similar trends were observed. In general, at both flow rates, an increase in FPF was noted going from the shallowest to the steepest ramp. However, there were no significant differences in FPF when a 2 L inhaled volume was compared with a 4 L volume at each flow rate. Overall, these data suggest that the existing USP apparatus may overestimate FPF at flow rates lower than those recommended by the USP.