Considerations for the Development and Practice of Cascade Impaction Testing, Including a Mass Balance Failure Investigation Tree

Particle Size Analysis of Aerosols from Medicinal Inhalers

“…For instance, in a recently published standard by the Canadian Standards Association, the use of a low flow rate cascade impactor is specified for the purpose of evaluating spacer and valved holding chamber (HC) add-on devices with pMDIs that are intended for pediatric rather than adult use [20]. Precautions may also be taken to minimize the impact of surface electrostatic charge accumulation by the choice of metal to provide an electrically conductive surface, rather than non-conducting glass collection media in impactors [21], as well as by operating the equipment with climate control so that the ambient relative humidity is not too low. Control of relative humidity may also be important when testing spacers and holding chambers manufactured from non-conducting polymers, where electrostatic charge accumulation is important [22].…”

“…Recently a working group of the US Product Quality Research Institute (PQRI), which is a collaborative process involving representatives from the pharmaceutical industry, academia and the FDA, developed a guide to aid those testing inhalers by the cascade impaction method [21]. The underlying purpose of this document was to identify impactor-related contributions to the overall uncertainty of the mass balance of API that is used to validate the particle size measurement.…”

“…The choice of a suitable viscous surface coating to avoid particle bounce in a CI [79][80][81][82] is of critical importance when testing DPIs [83,84], with the exception of the MSLI, where the liquid contained in each impaction stage fulfils this purpose. The decision whether or not to coat, and with whatever substrate, is normally made during the development of the method for a particular inhaler/drug product 42 KONA No.22 (2004) [21]. A wide variety of such methods exist, and the European Pharmaceutical Aerosol Group (EPAG) has therefore recently published a summary of current procedures that are in use by member organizations [85].…”

“…Two types of TOF analyzer have been widely applied to the measurement of medical aerosols. Table 11 Potential causes of bias in impactor-based particle size measurements Ҁ Impactor-related issues † † adapted from [21]: used by permission, Mary Ann Liebert Inc. Potentially large, depending more on formulation (e.g.…”

Theory of Multi-Nozzle Impactor Stages and the Interpretation of Stage Mensuration Data

“…Another reason impactors are common tools for characterizing inhalable drug products is the ability to determine the chemical identity of the particles collected on each stage of the impactor, giving a reasonable understanding of whether the active pharmaceutical ingredient (API) is indeed present in particles that are likely to penetrate into the lung (Christopher et al 2003).…”