Overview

In contrast with our previous inline DPIs that are intended to operate with relatively high dispersion air volumes,^(3,9) the low air volume (or LV) devices developed in this study pass all of the available airflow through a capsule dose containment unit. The air source is a simple syringe connected via a luer lock fitting and filled with 10 mL of room air that is operated manually. Based on experiments with a number of preliminary concepts, the two leading LV designs are presented as Figures 1 and ​and2,2, respectively. A common feature in both devices is that metal capillary tubes pierce the capsule when the device is closed, forming an airtight flow path through the device. In one design, the airflow pathway is in a single direction, or straight through (ST) the capsule and device (Fig. 1). In the second design, the capillary-based inlet and outlet are on a single side (SS) of the capsule, resulting in a near 180-degree turn in the airflow path. In both designs, the outlet capillary directs aerosol through a flow channel with a final diameter of 7 mm. These two leading designs are optimized and compared in this study based on modifications to the inlet and outlet capillary properties. To improve dispersion of the 10 mg powder mass, we also introduce the concept of a dispersion ball placed inside the capsule. Use of a lightweight polytetrafluoroethylene (PTFE) dispersion ball is expected to create vibrational motion as observed in Farkas et al.⁽³⁰⁾ to enhance capsule emptying. As a representative EEG formulation, the new inline DPIs are tested with a previously described^(19,31) EEG formulation of AS. Using this formulation, previous inline DPIs have produced MMAD values as low as 1.47 μm with an ED value of 78.2% using high dispersion air volumes with approximately 1 L of air per actuation. The primary particle size of the EEG formulation is tested using a Sympatec (Sympatec GmbH, Clausthal-Zellerfeld, Germany) laser diffraction system with a RODOS aerosol dispersion accessory, which uses a pressure drop of 4 bar (400 kPa) to disperse a small amount of the powder. Aerosol characterization from the devices is based on drug quantification using high performance liquid chromatography (HPLC) analysis of the various DPI components to determine the ED and by cascade impaction using the Next Generation Impactor (NGI), to determine the FPF and MMAD. Further details of the devices, formulation, and characterization studies are provided in the following sections.

Axial cross section of the assembled ST device showing the inlet and outlet capillaries inside of the capsule. ST, straight-through.

Axial cross section of the assembled SS device showing the inlet and outlet capillaries inside of the capsule. SS, single-sided.