Effects of ramp-up of inspired airflow on in vitro aerosol dose delivery performance for certain dry powder inhalers

This study investigated the effect of airflow ramp-up on the dose delivery performance of seven dry powder inhalers, covering a broad range of powder formulations and powder dispersion mechanisms. In vitro performance tests were performed at a target pressure drop of 4 kPa, using two inspiratory flow ramp-up conditions, representing slow and fast ramp-up of airflow, respectively. The fluidization of bulk powder and aerosol clearance from the inhaler was assessed by laser photometer evaluation of aerosol emission kinetics and measurement of the delivered dose (DD). The quality of aerosol dispersion (i.e. de-agglomeration) and associated lung targeting performance was assessed by measuring the total lung dose (TLD) using the Alberta idealized mouth–throat model. The ratio of DD and TLD under slow/fast ramp conditions was used as a metric to rank-order flow ramp effects. Test results show that the delivered dose is relatively unaffected by flow ramp (DD ratio ~ 1 for all dry powder inhalers). In contrast, the total lung dose showed significantly more variation as a function of flow ramp and inhaler type. Engineered (spray dried) powder formulations were associated with relatively high TLD (> 50% of nominal dose) compared to lactose blend and agglomerate based formulations, which had a lower TLD (7–40% of nominal dose), indicative of less efficient targeting of the lung. The TLD for the Tobi Podhaler was the least influenced by flow ramp (TLD ratio ~ 1), while the TLD for the Asmanex Twisthaler was the most sensitive to flow ramp (TLD ratio ≪ 1). The relatively high sensitivity of the Asmanex Twisthaler to flow ramp is attributed to rapid aerosol clearance (from the inhaler) combined with a strong effect of flow-rate on particle de-agglomeration and resulting size distribution.

Graphical abstractEffect of inhaler ramp-up flow on delivery of dry powder aerosols to the lungs depends on interplay between formulation and device.Figure optionsDownload full-size imageDownload high-quality image (116 K)Download as PowerPoint slide