Do dry powder inhalers (DPIs) have a ‘Goldilocks Zone’ of inhalation? In vitro lung deposition of Budesonide/Formoterol (BUD/FORM) DPI with different inhalation profiles

Abstract

Introduction: Patients need to inhale forcefully when using a DPI to generate fine particle dose (FPD) for inhalation. However, fast inhalations may lead to increased impaction of drug in the mouth and throat. Aims & Objectives: This study examined the effect of inhalation flow on lung deposition with BUD/FORM DPI (AstraZeneca; Symbicort ® Turbuhaler ® ) using Functional Respiratory Imaging (FRI). Methods: 3D airway models of 6 asthma patients (mean FEV 1 83%) were included. Total lung (TLD), central (C) and peripheral (P) airway deposition of ICS/LABA were assessed using FRI. Deposition was assessed for 3 inhalation profiles (average flow rate 30, 60 and 180L/min; volume 3L) with the peak flow near the start of manoeuvre. Dose release time was 0.5s (Pharm Res (2012) 29:1670-1688); fine particle characteristics were matched to flow rate (Comb Prod Ther (2013) 3:39). Results: Low flow rate was associated with low TLD due to reduced FPD and increased particle size whereas a high flow rate, with increased FPD, also resulted in low TLD due to greater impaction in the extrathoracic region. 60 L/min produced highest levels of TLD. Two lower flow rates were associated with relatively greater P deposition than the high rate. Conclusions: These results suggest DPIs may be subject to a ‘Goldilocks Zone’ of inhalation with inhalation too slow or fast resulting in suboptimal drug delivery. This study was funded by Mundipharma International Ltd.