ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Respiratory Pharmacology
This article is part of the Research TopicResearch and Innovation Approaches to Personalized Pharmacotherapies for Respiratory DiseasesView all 11 articles
Prediction of Site-Specific Drug Deposition via Dry Powder Inhaler using Non-Invasive Real-Time Particle Emission Signal Monitoring System
Provisionally accepted
Sakiko Hatazoe1,2
Daiki Hira1*
Tetsuri Kondo3
Yuki Shigetsura1Natsuki Imayoshi1Yurie Katsube1Keiko Ikuta1Yuki Kunitsu1Keisuke Umemura1
Satoshi Hamada2Satoshi Ueshima4Shunsaku Nakagawa1Masahiro Tsuda1
Susumu Sato2
Mikio Kakumoto4Tomohiro Terada1- 1Kyoto University Hospital, Kyoto, Japan
- 2Kyoto Daigaku, Kyoto, Japan
- 3Shonan Fujisawa Tokushukai Byoin, Fujisawa, Japan
- 4Ritsumeikan Daigaku, Kyoto, Japan
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Background: Accurate evaluation of regional drug deposition within the respiratory tract is essential for optimizing inhalation therapy efficacy and minimizing adverse effects. However, non-invasive, real-time quantitative methods for site-specific drug delivery assessment remain limited. Objective: To develop mathematical models to predict site-specific drug deposition from a dry powder inhaler (DPI) using a non-invasive, real-time photo reflection method (PRM). Methods: Using Symbicort® Turbuhaler® as a model DPI, four inhalation patterns varying in peak flow rate (PFR: 30–60 L/min) and flow increase rate (FIR: 3.2–9.6 L/s²) were simulated using a human inhalation flow simulator. Aerodynamic particle deposition of budesonide was quantified as the fine particle fraction for the whole lung (FPFWL), peripheral airways (FPFPA), and oropharyngeal region using an Andersen Cascade Impactor. Particle emission signals were monitored via PRM. The relationship between particle emission signals and deposition performance was analyzed using four univariate models: linear, logarithmic, Hill, and Emax. Results: Increased PFR and FIR enhanced drug deposition in both the lungs and oropharyngeal region. FPFWL and FPFPA were strongly correlated with total particle emission intensity over time with the Hill model (R² = 0.86 and 0.74 for FPFWL and FPFPA, respectively), reflecting nonlinear deagglomeration. Oropharyngeal deposition correlated with flow rate at particle emission peak, fitting a linear model (R² = 0.82), consistent with inertial impaction mechanisms. Conclusions: Using an in-vitro model, particle emission signals enable the prediction of site-specific drug deposition from DPI, providing non-invasive, real-time indices and offering personalized inhalation performance assessment beyond conventional flow rate metrics.
Keywords: Dry powder inhaler, non-invasive, photo reflection method, Real-time monitoring, site-specific drug deposition
Received: 23 Dec 2025; Accepted: 04 Feb 2026.
Copyright: © 2026 Hatazoe, Hira, Kondo, Shigetsura, Imayoshi, Katsube, Ikuta, Kunitsu, Umemura, Hamada, Ueshima, Nakagawa, Tsuda, Sato, Kakumoto and Terada. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Daiki Hira
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