The effect of inhalation delay on the aerodynamic particle size distribution of fluticasone propionate and ciclesonide using pMDI and valved holding chambers

Delayed inhalation when using pressurised metered-dose inhalers (pMDIs) for inhaled corticosteroids (ICS) is a common technique error. Valved holding chambers (VHCs) can mitigate its impact, but the effect of delays on drug delivery from suspension versus solution formulations remains poorly understood. We compared the doses of fluticasone propionate (FP) and ciclesonide (CIC) delivered to an anatomical adult throat model and a Next Generation Impactor as particles 1-5 μm and under 1 μm in diameter, using AeroChamber (AC), EasyChamber (EC), and OptiChamber Diamond (OD) VHCs with inhalation delays of 0, 1, 3, and 5 s. A breathing simulator was used to produce a single, adult-type inhalation. Throat deposition gradually decreased with longer inhalation for both FP and CIC, from an average of 3.3 %-2.2 % and 1.0 %-0.5 % of the label claim, respectively. Similarly, deposition of 1-5 μm particles declined from 30 % to 28 % for FP and from 33 % to 25 % for CIC. In contrast, deposition of particles smaller than 1 μm were relatively unaffected by inhalation delays. In conclusion, increasing the inhalation delay up to 5 s slightly reduced the respirable deposition of FP and CIC particles when using a VHC, but these reductions are unlikely to be clinically meaningful due to small differences in absolute dose. The smallest particles likely remained unaffected by the delay due to their low tendency to settle. Differences in performance between AC, EC, and OD during the delay were likely too minor to influence treatment outcomes.