Issue link: https://www.e-digitaleditions.com/i/1475629
Inhalation August 2022 27 devices. In this context, it is relevant to bring up the interplay between the formulation and the flow rate reported by researchers at the University of Groningen [16, 17]. For the systems studied, sigmoidal flow rate dependencies were obtained when analyzed in a pro- totype inhaler equipped with a cyclone mouthpiece. As illustrated in Figure 4, a crossover in FPF perfor- mance can occur as function of flow rate, i.e., at a low flow rate, the formulation with low drug load gives the highest FPF, while at high flow rates, the situa- tion is reversed. is phenomenon can be understood by realizing that above a certain drug load, the API particles start to form a connected layer at the carrier surfaces that requires additional energy to break up. Such networks of connected API particles were also demonstrated by the Groningen authors [17]. erefore, to avoid flow rate sensitive formulations, it is recommended that FPF studies be performed at different flow rates/pressure drops early in the devel- opment process. If a sigmoidal dispersibility profile is found, it should be ascertained that flow rates/pres- sure drops achieved by patients fall above the zone with the steep FPF increase. As further demonstrated by the Groningen authors, similar effects can occur due to the presence of lactose fines. When 4% fine lactose (named FLF in their paper) was added to a 0.4% Bud formulation, the FPF versus flow rate curve changed from monotonic to sigmoidal [18]. Again, this points towards the total amount of fine particles, i.e., API(s) plus fine lactose, as a critical parameter for formulation performance. A final challenge for multi-dose devices is to avoid retention and build-up of the API within the device. is may prove challenging for devices that have strong deaggregation capability due to inertial impaction on device surfaces, which tend to have more powder build-up and, therefore, higher lev- els of drug retention in the device. Cleaning of the mouthpiece may therefore be required, unless a dis- posable device is used.