Development of high efficiency ventilation bag actuated dry powder inhalers

Abstract

New active dry powder inhaler systems were developed and tested to efficiently aerosolize a carrier-free formulation. To assess inhaler performance, a challenging case study of aerosol lung delivery during high-flow nasal cannula (HFNC) therapy was selected. The active delivery system consisted of a ventilation bag for actuating the device, the DPI containing a flow control orifice and 3D rod array, and streamlined nasal cannula with separate inlets for the aerosol and HFNC therapy gas. In vitro experiments were conducted to assess deposition in the device, emitted dose (ED) from the nasal cannula, and powder deaggregation. The best performing systems achieved EDs of 70-80% with fine particle fractions <5 μm of 65-85% and mass median aerodynamic diameters of 1.5 μm, which were target conditions for controlled condensational growth aerosol delivery. Decreasing the size of the flow control orifice from 3.6 to 2.3mm reduced the flow rate through the system with manual bag actuations from an average of 35 to 15LPM, while improving ED and aerosolization performance. The new devices can be applied to improve aerosol delivery during mechanical ventilation, nose-to-lung aerosol administration, and to assist patients that cannot reproducibly use passive DPIs.

Keywords: Active dry power inhaler (DPI); Excipient enhanced growth (EEG) formulation; High efficiency DPI; Noninvasive ventilation; Nose to lung aerosol delivery; Streamlined ventilation components.

Figure 1

The active dry powder inhaler (DPI) system including a ventilation bag, flow meter (for experimental testing only), inline DPI (containing a flow control orifice and 3D rod array), and streamlined nasal cannula.

Figure 2

Inline DPI devices consisting of a flow control orifice (3.6 - 2.3 mm diameter), capsule chamber, restraining mesh, 3D rod array and flow passage that connects to 10 mm diameter ventilator tubing. Different flow control orifice size and rod array pattern configurations were considered including (a) 3.6 mm orifice and 5-6-5 rod array pattern, (b) 3.1 mm orifice and 5-6-5 rod array pattern, (c) 2.3 mm orifice and 3-4-3 rod array pattern, and (d) 2.3 mm orifice and 2-1-2 rod array pattern.

Figure 3

Illustration of the DPI (a) with and (b) without connective tubing leading to the ECG cannula. The length of the connective tubing in Panel (a) is not draw to scale. In the experiments, only the 3.6–565 DPI contained a 13 cm length of 10 mm diameter connective tubing between the device and ECG cannula. The other devices implemented a much shorter (~1 cm) length or eliminated the connective tubing.

Figure 4

Connection of the previously optimized passive CC₉₀-3D inhaler used for oral inhalation to the ECG cannula. In this setup, the CC₉₀-3D inhaler was operated by connecting the flow delivery line to the inlet orifice above the capsule chamber.

Figure 5

Capsule piercing apertures with different configurations denoted (a) Case 1, (b) Case 2, (c) Case 3, (d) Case 4, and (e) Case 5. Direction of flow during operation and the restraining mesh are illustrated in Panel (a). Apertures with a diameter of 0.5 mm were located at the top (or bottom) of the capsule, midway the head (or base) curvature, and at the start of the head (or base) curvature.

Figure 6

Divided ECG cannula for dual stream aerosol delivery during HFNC therapy. During aerosol administration, the aerosol stream from the DPI enters one side of the cannula and flows through a streamlined passage into one nasal prong. High flow therapy (heated and humidified) gas enters the other nasal prong.