Importance of Powder Residence Time for the Aerosol Delivery Performance of a Commercial Dry Powder Inhaler Aerolizer®

Abstract

The performance of dry powder aerosol delivery systems depends not only on the powder formulation but also on the dry powder inhalers (DPIs). Effects of turbulence, grid, mouthpiece, inlet size, air flow, and capsule on the DPIs performance have been investigated previously. Considering powder dispersion in DPIs is a time-dependent process, the powder residence time in DPIs is supposed to have a great impact on DPIs efficiency. This study sought to investigate the effect of powder residence time on the performance of a commercial DPI Aerolizer(®). A standard Aerolizer(®) (SD) and five modified devices (MD1, MD2, MD3, MD4, and MD5) were employed for this research. Computational fluid dynamics analysis was used to calculate the flow field and the powder residence time in these devices. Recombinant human interleukin-2 inhalation powders and a twin impinger were used for the deposition experiment. The powder mean residence time in the secondary atomization zone of the devices was increased from 0 ms for SD to 0.33, 0.96, 1.42, 1.76, and 2.14 ms for MD1, MD2, MD3, MD4, and MD5, respectively. At a flow rate of 60 L/min, with an increase in the powder residence time in these devices, a significant gradual and increasing trend in the powder respirable fraction was observed from 29.1%± 1.1% (MD1) to 32.6% ± 2.2% (MD2), 37.1% ± 1.1% (MD3), and 43.7% ± 2.1% (MD4). There was no significant difference in the powder respirable fraction between SD and MD1 or between MD4 and MD5. Within a certain range, increasing the powder residence time could improve the performance of Aerolizer(®) by increasing the powder-air interaction time (the main reason) and increasing the powder-device compaction (the secondary reason). Combination of high turbulence level and sufficient powder residence time could further improve the device performance.