- Author(s):
- Organization(s):
cystetic Medicines, Inc. Plastiape, S.p.A., a Berry Global Company University of Illinois
This in vitro study evaluated how rational selection of device resistance can be used to minimize flow rate dependence in dose delivery in vivo. Aerosol performance of amphotericin B inhalation powder was assessed using a Next Generation Impactor (NGI) at a range of pressure drops (1, 2, 4 and 6 kPa) with low, medium, high, and ultrahigh resistance variants of the RS01 dry powder inhaler (DPI).
For this powder, both powder fluidization and powder dispersion were highly dependent on pressure drop/inspiratory flow rate. Flow rate dependence in deposition on stage 3 to filter, a metric for delivery to the lower respiratory tract, was effectively mitigated by increasing device resistance. The selection of the ultrahigh resistance RS01 variant allowed the increased capsule retention and device deposition at low flow rates to be balanced by reduced deposition in the coarse fraction representing deposition in the United States Pharmacopeia (USP) throat to stage 2 in the NGI. In contrast, with the low resistance RS01 variant, increases in inertial impaction in the coarse fraction with increases in flow rate dominated over variations in device deposition, resulting in a marked decrease in stage 3 to filter deposition. Therefore, selection of the ultrahigh resistance RS01 variant enabled consistent in vitro dose delivery based on stage groupings between 1 and 6 kPa.