Next Generation Pharmaceutical Impactor: A New Impactor for Pharmaceutical Inhaler Testing. Part III. Extension of Archival Calibration to 15 L/min

Abstract

An extension of the archival calibration of the recently developed 30-100-L/min seven-stage impactor, the Next Generation Pharmaceutical Impactor (NGI), has been undertaken at 15 L/min. The NGI stage cut sizes are 0.98-14.1 microm aerodynamic diameter at this flow rate. This 15-L/min calibration was motivated by the desire to sample the entire aerosol produced by a nebulizer when tested in accordance with a new international standard developed by the Comite Européen de Normalisation (CEN), as well as the need to test various types of inhalers at flow rates lower than 30 L/min for pediatric applications. Measurements were undertaken with monodisperse oleic acid droplets in the range of 0.7-22 microm aerodynamic diameter following a procedure established in the original 30-100-L/min calibration study. The NGI was found to be effective for particle size separation at 15 L/min. Users should decide the most applicable configuration that meets their needs, based on the following recommendations: (1) the pre-separator should not normally be used, as its performance is significantly degraded by the influence of gravity, resulting in interference with stage 1; and (2) a filter should be inserted below the micro-orifice collector (MOC), as the size corresponding to 80% collection efficiency of the MOC becomes excessively large with decreasing flow rate, so that this component becomes ineffective as a means of collecting fine particles that penetrate beyond stage 7.

A sampling and dilution system for droplet aerosols from medical nebulisers developed for use with an optical particle counter

“…Marple et al (2004) describe the NGI as a suitable method for nebuliser testing in accordance with CEN Standard 13544 (2001) if the impactor is used without a preseparator and an additional filter is placed behind the micro-orifice collector. This extra filter is necessary because the collection efficiency of the micro-orifice collector decreases with the decreasing Reynolds number observed at an air flow rate of 15 L/min.…”

“…The European Standard for respiratory therapy equipment suggests two separate methods for aerosol characterisation: the multistage cascade impactor and laser diffraction for particle sizing and an additional method for testing the aerosol output rate (CEN, 2001). Following the successful development of the Next Generation Impactor (NGI), the extension of the calibration to 15 L/min allowed the use of this impactor in the characterisation of aerosols from nebulisers (Marple et al, 2004). The new monograph 2.9.44 proposed for the European Pharmacopoeia (Ph.…”

Rapid Check of Cascade Impactor Cut-Sizes using a Polydisperse Challenge Aerosol Calibration Method

“…The cascade impactor was the Next Generation Pharmaceutical Impactor (NGI) (Marple et al 2003a) that had recently been calibrated by our laboratory (Marple et al 2003b(Marple et al , 2004 employing Good Laboratory Practice (GLP) procedures (21 CFR Part 58, 1987). In addition, the latest calibration procedures of our Particle Calibration Laboratory (PCL) were employed.…”

Good Cascade Impactor Practice (GCIP) and Considerations for “In-Use” Specifications

“…The Next Generation Impactor (NGI) was purposedesigned and calibrated by an industry consortium at 30, 60, and 100 L/min for the assessment of pMDI and DPI products (20), with its operating range later extended to 15 L/min for the assessment of nebulizing systems (40). One of the key criteria underlying its design was that it would have better aerodynamic particle size-separating capability (sharper, nonoverlapping, stage collection efficiency curves) than those of the Andersen eight-stage CI.…”