A cross-industry assessment of the flow rate-elapsed time profiles of test equipment typically used for dry-powder inhaler (DPI) testing: Part 2– analysis of transient air flow in the testing of DPIs with compendial cascade impactors

We describe a computational model that captures the physics of the unsteady airflow start-up that accompanies the testing of dry-powder inhalers (DPI) with cascade impactors (CIs) specifically when following methods described in the pharmacopeial compendia. This transient has been measured in a multi-organization study for a wide range of conditions and reported in a companion article. The DPI test system is simulated as a series of flow resistances, starting with the inhaler itself, including each stage of the CI, and finishing with the prescribed flow control valve, wherein the flow is held at sonic Accepted Manuscript m SA Kingdom ited Kingdom Kingdom ted Kingdom Kingdom c., London, Ontari , United Kingdom nited Kingd @gmail.com gmail.comMJolyo ondon, ON, Canad , C be a computationa omputatio up that accompan that accom ctors (CIs) specifi ors (CIs) spe ia. This a velocity. The resulting non-dimensional equations indicate the relative importance of the several flow resistances. The model agrees well with the available experimental data for the Next Generation Impactor (NGI™) and qualitatively with the available data from a variety of the configurations of the Andersen 8-stage cascade impactor (ACI), including the typical 4-kPa pressure drop across an entry fixed orifice mimicking surrogate low-, medium- and high-resistance DPIs. The model indicates that the start-up times for the NGI and for the ACI are very reasonably estimated by a simple “reference time,” given in equation (26) and, for an inlet flow rate of 60 L/min, having a value of 277 ms and 113 ms for the NGI and ACI (60-L/min configuration), respectively. The model also enables a baseline, universal design curve for the flow rise-time performance of testing DPIs with the NGI (Figures 9a,b), because this impactor requires no change of components for any inlet flow rate

A cross-industry assessment of the flow rate-time profiles of test equipment typically used for dry-powder inhaler (DPI) testing: Part 1 – compendial apparatuses

We report a cross-industry study characterizing flow rate-time profiles of equipment used for testing dry-powder inhalers (DPIs). Nine organizations used the same thermal mass flow sensor to record flow rate-time profiles at the inlet of individual participant compendial DPI test systems including either sample collection tubes (SCT), the Andersen 8-stage non-viable impactor (ACI) or the Next Generation Impactor (NGI™) with and without pre-separator (PS). The plan included some tests with a surrogate DPI consisting of one of three inlet orifices chosen to generate a 4-kPa pressure drop at each of the target final flow rates of 30, 60, and 90 l.min−1, simulating the pressure drop typical of high-, medium-, and low-resistance DPIs. When a particular surrogate DPI was present at the inlet, rise times to 90% of these target flow rates (t90) were shortest at the highest target flow rate, and decreased linearly with decreasing apparatus internal volume, following the order: NGI-PS>NGI>ACI-PS>ACI>SCT. A flow acceleration parameter was also evaluated, expressed as the slope between the rise times when the flow rate attained 20% and 80% of each final steady flow rate (slopet20/80). Flow acceleration was smallest at the lowest target flow rate, decreasing exponentially with increasing internal volume. Measurements were also made without the surrogate DPI, providing a reference condition with no resistance at the inlet to the apparatus. These flow rate-rise time profiles will be useful for those involved in evaluating equipment for characterizing DPIs and in understanding the behavior of these inhalers in development or commercial production