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

Abstract

Abstract. The multi-stage cascade impactor (CI) is widely used to determine aerodynamic particle size distributions (APSDs) of orally inhaled products. Its size-fractionating capability depends primarily on the size of nozzles of each stage. Good Cascade Impactor Practice (GCIP) requires that these critical dimensions are linked to the accuracy of the APSD measurement based on the aerodynamic diameter size scale. Effective diameter (D eff ) is the critical dimension describing any nozzle array, as it is directly related to stage cut-point size (d 50 ). d 50 can in turn be determined by calibration using particles of known aerodynamic diameter, providing traceability to the international length standard. Movements in D eff within manufacturer tolerances for compendial CIs result in the worst case in shifts in d 50 of <±10%. Stage mensuration therefore provides satisfactory control of measurement accuracy. The accurate relationship of D eff to d 50 requires the CI system to be leak-free, which can be checked by sealing the apparatus at the entry to the induction port and isolating it from the vacuum source and measuring the rate of pressure rise before each use. Mensuration takes place on an infrequent basis compared with the typical interval between individual APSD determinations. Measurement of stage flow resistance (pressure drop; ΔP stage ) could enable the user to know that the CI stages are fit for use before every APSD measurement, by yielding an accurate measure of D eff . However, more data are needed to assess the effects of wear and blockage before this approach can be advocated as part of GCIP.

Particle sizing of pharmaceutical aerosols via direct imaging of particle settling velocities

“…1a). While the geometry of the induction port is known to have a significant influence on particle size distributions due to particle deposition and agglomerate breakup (Dolovich and Rhem, 1998; Nichols et al, 2013), we chose in a first step to use a straight tube in order to maximize the amount of particles imaged inside the prototype. Nevertheless, we closely matched the diameter and total length of the tube to the standard L-shaped induction port (European Pharmacopeia, 2008).…”

Determination of Passive Dry Powder Inhaler Aerodynamic Particle Size Distribution by Multi-Stage Cascade Impactor: International Pharmaceutical Aerosol Consortium on Regulation & Science (IPAC-RS) Recommendations to Support Both Product Quality Control and Clinical Programs

“…Apparatus maintenance includes the induction port, preseparator, and induction port, and its focus is chiefly on periodic (i.e., annual) CI performance validation through stage mensuration (83), whereby optical microscopy combined with automated image analysis is used to determine the individual nozzle diameters of each stage. Mechanical go-no go gauges can be used for checking nozzles > ca.…”

Aerosol Delivery of siRNA to the Lungs. Part 1: Rationale for Gene Delivery Systems

“…The available cascade impactors accepted by the United States Pharmacopeia (USP) and the European Pharmacopeia (Ph.Eur.) are listed in Table 3 (Mitchell J.P. et al, 2010;Nichols S.C. et al, 2013). The Andersen Cascade Impactor (ACI) is a pharmacopeial method for pMDIs and DPIs and is the most commonly used inertial impactor instrument (Fig.…”

“…Nebulizers are suggested to be characterized by the USP <601>/ Ph.Eur. 2.9.44 using the Next-Generation Impactor (NGI) at 15 L/min or with a suitable validated cascade impactor that operates at ≤15 L/min (Nichols S.C. et al, 2013).…”