A European Pharmaceutical Aerosol Group (EPAG)-Led Cross-Industry Assessment of Inlet Flow Rate Profiles of Compendial DPI Test Systems: Part 1 – Experimental Data
Jolyon P Mitchell1, Chris Blatchford2, Roland Greguletz3, Daryl L. Roberts4, & Henk Versteeg5
1 Jolyon Mitchell Inhaler Consulting Services Inc., 1154 St. Anthony Road, London, N6H 2R1, Canada
2 3M United Kingdom plc, Loughborough, LE11 5RB, UK
3 Sofotec GmbH, Benzstraße 1-3, Bad Homburg, D-61352, Germany
4 Applied Particle Principles LLC, 17347 Westham Estates Court, Hamilton, VA 20158, USA
5 Mechanical and Manufacturing Engineering, Loughborough University, Loughborough, LE11 3TU, UK.
We report outcomes from an EPAG-led cross-industry study, characterizing flow rate/elapsed-time profiles of equipment used for testing dry powder inhalers (DPIs). A thermal mass flow sensor was used by nine organizations in a round-robin approach to record inlet flow rate-time profiles of individual participant compendial test systems (TS) including either sample collection tubes (SCT) or a cascade impactor (either the Andersen 8-stage non-viable impactor, ACI, or the Next Generation Impactor, NGI) equipped with USP/PhEur induction port and pre-separator. An inlet orifice generated a 4-kPa pressure drop at each of the target flow rates (30, 60 and 90 L/min), simulating a pressure drop typical for high-, medium- and low-resistance DPIs respectively. Rise times to 90% of these target flow rates (t90) were longest with largest internal dead volume and followed the order NGI>ACI >SCT>TS. When the surrogate DPI (4-kPa orifice) was absent, t90 values generally lengthened with increasing target flow rate. In contrast, the opposite behaviour was observed when the surrogate DPI was present. A flow acceleration parameter was also calculated, expressed as the slope between the 20% and 80% flow rates of each final steady flow value (slopet20/t80). Greater flow acceleration occurred at higher final flow rates, irrespective of apparatus, but the presence of the surrogate DPI was associated with slower flow acceleration. These flow rate-rise time profiles will be useful for those involved in evaluating equipment for characterizing both existing and new DPIs.