ABSTRACT
The European Pharmaceutical Aerosol Group (EPAG) has undertaken investigations with the aim of developing robust methods for the droplet size analysis of nebuliser-produced aerosols in support of the proposed European Pharmacopeia general chapter 2.9.44 covering preparations for nebulisation. A multi-centre study was designed to investigate the effects of cooling the Next Generation pharmaceutical Impactor (NGI) before sample collection, as a means of reducing bias and variability caused by heat transfer-related evaporation. Droplets containing salbutamol were sized from 3 different nebulisers chosen to offer fundamentally different modes of aerosol generation: AeroNeb Go, a vibrating mesh nebuliser; PARI LC Plus, a breath-enhanced jet nebuliser; and MistyMax, a constant-output jet nebuliser. Each laboratory undertook determinations at ambient temperature, using an NGI pre-cooled in a refrigerator (5 degrees C for at least 90 min). The corresponding measurements were made using an ambient NGI as a benchmark. Salbutamol solution 5 mg/2 ml (Teva, Runcorn, UK) was used throughout the study. Analysis of individual and pooled results from 5 of the participants showed a similar trend insofar as the cooled NGI yielded a coarser nebulised aerosol than that obtained by the ambient NGI. Mass Median Aerodynamic Diameter (MMAD) was on average reduced by 9.5-21.9 % and the Fine Droplet Fraction < 5 microm (FDF) increased on average by 5.5-17.4 % for all the nebuliser designs when comparing ambient to cooled NGI. Despite the more laborious procedure of cooling the NGI, variability in data was generally similar to that obtained with the ambient NGI. We conclude that it is beneficial to cool the NGI when sizing nebulised aerosol. Furthermore, occasional findings during this study revealed a build-up of solute deposits within the interior of the NGI, and a more rigorous impactor cleaning/drying procedure is therefore recommended.
