Correcting Photo Reflection Method Output and Its Application in the Dynamic Analysis of Particle Release from Dry Powder Inhalers.

Background: The photo reflection method (PRM) is used to measure light reflected from particles released from dry powder inhalers (DPIs). This simple method depicts time trajectories of released drugs; however, it underestimates the number of particles at high peak inhalation flow rates (PIFs). In this study, we aimed to correct this underestimation and clarify whether long inhalation is necessary for capsule-type DPIs, using this unique method. Methods: To establish quantitative measurements using the PRM, several types of DPIs were inhaled with square-wave inhalations at different PIFs using an inhalation simulator, and the total emitted dose (TED) and the release time of the TED (TTED) were measured. Next, capsule-type DPIs were inhaled using inhalation patterns of patients with chronic obstructive pulmonary disease (COPD), and particle release time trajectories were recorded. Results: For all DPIs, except for Turbuhaler® (TBH), both TED and TTED were hyperbolically decreased with an increase in the PIF of square-wave inhalations. TED correction using the TTED showed flat TED changes at high PIF ranges. The patient inhalation analysis showed that the corrected TEDs of seven COPD inhalation patterns were not significantly different. The PRM further revealed that the inhaled flow rate and release time of all seven patterns were sufficient to release particles in the capsule. Conclusions: The inhaled flow rate and TTED that exceeded specific conditions enabled complete particle release from the DPIs except for TBH. Therefore, an extremely long inhalation is not required for capsule-type DPIs. Our corrected time trajectory analysis using the PRM provides a new strategy for the particle release analysis of DPIs.