Characterisation of high dose dry powder aerosols by cascade impaction and laser diffraction analysis

Background: Developments in high dose dry powder inhalationcontinue to challenge the viability of pharmacopoeialmethods for drug aerosol characterisation. Especiallythe occurrence of bounce effects can cause the amount offines (<1 lm) to be highly overestimated in particle sizedistributions (PSDs) obtained by cascade impaction (CI).Methods: In this study the most suitable technique for thecharacterisation of dry powder aerosols from the Twincerainhaler containing 5-50mg of colistin sulphomethate hasbeen determined. To investigate the occurrence of bounceeffects, results from cascade impaction analysis with theNext Generation Impactor (NGI) and the Multi Stage LiquidImpinger (MSLI) have been compared with data from laserdiffraction analysis.Results: In the MSLI bounce effects do not occur, but thelow number of stages severely limits accurate data interpretation.With the NGI used with a standard impactionplate coating the particle fraction <1 μm is higher than whatcan be expected from RODOS dispersion data for all dosesdispersed. Only when solvent soaked glass fibre filters areused as an impaction surface in the NGI, bounce effects areminimised and PSDs obtained with this impactor are verysimilar to those from laser diffraction.Conclusions: Bounce effects can be minimised when testinghigh dose dry powder aerosols from the Twincera withthe MSLI and NGI. A reduced measurement time, a higherreproducibility and a greater number of size classes in theparticle size range of interest for inhalation make laser diffractiona very useful alternative technique for developmentpurposes.