Pharmacopeial methodologies for determining aerodynamic mass distributions of ultra-high dose inhaler medicines.

Three different impactor methodologies, the Andersen cascade impactor (ACI), next-generation impactor (NGI) and multistage-liquid impinger (MSLI) were studied to determine their performance when testing ultra-high dose dry powder formulations. Cumulative doses of spray-dried mannitol (Aridol) were delivered to each impactor at a flow rate of 60Lmin(-1) (up to a max dose of 800mg delivering 20 sequential 40mg capsules). In general, total drug collected in both the ACI and NGI falls below the range 85-115% of label claim criteria recommended by the United States of America Food and Drug Administration (FDA) at nominal mannitol doses exceeding 20mg and 200mg, respectively. In comparison analysis of the MSLI data, over a 5-800mg cumulative dosing range, indicated that the percentage of nominal dose recovered from the MSLI was within the +/-15% limits set in this study. Furthermore all samples, apart from the 5mg and 10mg analysis were within 5% of the nominal cumulative dose. While the MSLI is not routinely used for regulatory submission, the use of this impinger when studying ultra-high dose formulations should be considered as a complementary and comparative source of aerosol deposition data.