A European Pharmaceutical Aerosol Group (EPAG)-Led Cross-Industry Assessment of Inlet Flow Rate Profiles of Compendial DPI Test Systems: Part 2 – First-Order Impactor Model
Daryl L. Roberts1, Henk Versteeg2, Chris Blatchford3, Roland Greguletz4, Jolyon P. Mitchell5
1 Applied Particle Principles LLC, 17347 Westham Estates Court, Hamilton, VA 20158, USA
2 Mechanical and Manufacturing Engineering, Loughborough University, Loughborough, LE11 3TU, UK
3 3M United Kingdom plc, Loughborough, LE11 5RB, UK
4 Sofotec GmbH, Benzstraße 1-3, Bad Homburg, D-61352, Germany
5 Jolyon Mitchell Inhaler Consulting Services Inc., 1154 St. Anthony Road, London, N6H 2R1, Canada
A simple two-compartment, first-order flow resistance model of a cascade impactor reveals the reasons for the major trends observed in the companion, cross-industry study of the transient behaviour of the inlet flow rate in compendial DPI test systems. This model is physically reasonable because most of the internal volume of compendial impactors is comprised of stages with rather small resistance to flow, and when no DPI is attached to the induction port, the major flow resistance is contributed by the final one or two stages of the impactor. The typical DPI, then, with approximately 4-kPa pressure drop at the sampling flow rate, changes this situation by placing a significant flow resistance upstream of the otherwise insignificant resistance of the bulk of the impactor volume. Results with the two-compartment model reasonably agree with the experimental data in three important aspects: (a) the substantial increase in rise time when a surrogate DPI is present, (b) the decrease in rise time as the steady-state flow rate increases but only if the surrogate DPI is present (and opposite to the observed trend when the surrogate DPI is absent), and (c) the increase in rise time with larger total internal volume of the test equipment.
Compared with three-dimensional, unsteady-state numerical solutions of flow rate behaviour at start-up, the simple model intuitively conveys important physics that will assist users in understanding compendial DPI quality control test results, which could be very helpful when a user experiences unexpected trends or outliers in a data set.