In vitro evaluation of the DP-4M PennCentury insufflator.

Dry powder formulations for inhalation have to be screened in animal studies for therapeutic efficacy and safety aspects and both are significantly affected by the dose and the particle size distribution (PSD) of the aerosol that is given. One of the most frequently used apparatus for pulmonary delivery of dry powder formulations in mice studies is the PennCentury DP-4M Dry Powder Insufflator. To make researchers of future preclinical animal studies with the DP-4M insufflator aware of the pitfalls regarding the conclusions to be drawn from their data, we investigated the dispersion behaviour by the DP-4M insufflator using two to three different powder preparation techniques for four different compounds. The primary PSDs of the different formulations were determined in duplicate by laser diffraction analysis. To measure the PSDs of the aerosols obtained with the DP-4M insufflator, the same diffractometer was used in combination with an in-house constructed adapter for the insufflator. The dispersion efficiency and delivered dose were highly affected by the amount of air available for dispersion; the 200 μL of air recommended for the type of insufflator used was insufficient for adequate dispersion. In contrast, the weighed dose did not have a profound effect on the dispersion behaviour and the delivered dose of the DP-4M insufflator. Also the physico-chemical powder properties and the applied particle preparation technique influenced the amount and PSD of the delivered aerosol only to a limited extend, with a few exceptions. We advise researchers to investigate the dispersion efficiency and delivered dose from the DP-4M insufflator with the formulation under investigation prior to in vivo studies and it may be necessary to optimise the formulation for administration to mice.