College of Pharmaceutical Sciences, Ritsumeikan University, Kusatsu, Shiga, Japan.
Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, 54 Shogoin Kawahara-Cho, Sakyo-Ku, Kyoto, 606-8507, Japan.
AAPS PharmSciTech. 2024 May 10;25(5):109. doi: 10.1208/s12249-024-02825-7.
Although inhalation therapy represents a promising drug delivery route for the treatment of respiratory diseases, the real-time evaluation of lung drug deposition remains an area yet to be fully explored. To evaluate the utility of the photo reflection method (PRM) as a real-time non-invasive monitoring of pulmonary drug delivery, the relationship between particle emission signals measured by the PRM and in vitro inhalation performance was evaluated in this study. Symbicort® Turbuhaler® was used as a model dry powder inhaler. In vitro aerodynamic particle deposition was evaluated using a twin-stage liquid impinger (TSLI). Four different inhalation patterns were defined based on the slope of increased flow rate (4.9-9.8 L/s) and peak flow rate (30 L/min and 60 L/min). The inhalation flow rate and particle emission profile were measured using an inhalation flow meter and a PRM drug release detector, respectively. The inhalation performance was characterized by output efficiency (OE, %) and stage 2 deposition of TSLI (an index of the deagglomerating efficiency, St2, %). The OE × St2 is defined as the amount delivered to the lungs. The particle emissions generated by four different inhalation patterns were completed within 0.4 s after the start of inhalation, and were observed as a sharper and larger peak under conditions of a higher flow increase rate. These were significantly correlated between the OE or OE × St2 and the photo reflection signal (p < 0.001). The particle emission signal by PRM could be a useful non-invasive real-time monitoring tool for dry powder inhalers.
虽然吸入疗法是一种很有前途的治疗呼吸系统疾病的药物输送途径，但肺部药物沉积的实时评估仍然是一个尚未充分探索的领域。为了评估光反射法（PRM）作为实时非侵入性监测肺部药物输送的效用，本研究评估了 PRM 测量的颗粒发射信号与体外吸入性能之间的关系。Symbicort® Turbuhaler®被用作模型干粉吸入器。使用双级液体撞击器（TSLI）评估体外空气动力学颗粒沉积。根据流量增加率（4.9-9.8 L/s）和峰值流量（30 L/min 和 60 L/min）的斜率，定义了四种不同的吸入模式。使用吸入流量计和 PRM 药物释放检测器分别测量吸入流量和颗粒排放曲线。通过输出效率（OE，%）和 TSLI 第 2 级沉积（表示解聚效率的指标，St2，%）来描述吸入性能。OE×St2 定义为输送到肺部的量。在吸入开始后 0.4 s 内，四种不同吸入模式产生的颗粒排放即完成，在较高流量增长率条件下，观察到更尖锐和更大的峰值。OE 或 OE×St2 与光反射信号之间存在显著相关性（p<0.001）。PRM 的颗粒发射信号可能是干粉吸入器的一种有用的实时非侵入性监测工具。
