Comparison Between Pharmacopeial Testing and Testing Based on Mixing Inlet Lung Simulator (MILS) Methodology with Application to Nebuliser Testing: Part 1 – Pilot Study to Select Most Feasible MILS Method

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The compendial approach to determine fine particle dose (FPD) for nebulisers during simulated tidal breathing is to determine delivered dose (DD) for tidal breathing, while fine particle fraction (FPF) is established separately using a cooled Next Generation Impactor (NGI) operated at 15 L/min. FPD is then calculated as the product of DD and FPF. An advance in mixing inlet lung simulation (MILS) methodology has made it possible for both measurements to be combined in a single configuration. A comparison of the MILS procedure against the combination of pharmacopeial methods using the eFlow® Rapid vibrating membrane nebuliser as device representative of this class of orally inhaled products (OIPs) is reported as Part 2 of the overall investigation. However, a preliminary study was needed before this comparison could take place, since the operating flow rate for the NGI when used with the mixing inlet has to be greater than the peak inspiratory flow rate (PIFR) of 24 L/min of the selected adult breathing pattern. The primary purpose of this pilot study was to establish and minimize the influence of a NGI flow rate change from 15 to 30 L/min. At the same time the investigation was extended to examine possible influences of the relative humidity of the pressurized air supply to the mixing inlet as well as whether or not the impactor needed to be cooled. It was found that the best performing configuration is to operate the NGI cooled (5ºC) with humidified air (90-92%RH) supplied to the mixing inlet.