Optimizing Cascade Impactor Testing for Characterizing Orally Inhaled & Nasal Drug Products

Although the information set out here focuses (because of their market leading positions) on the Andersen Cascade Impactor (ACI) and Next Generation Impactor (NGI), all multistage cascade impactors operate on the same principle: size fractionation on the basis of inertial impaction. Instruments such as the ACI and NGI consist of a series of stages each made up of a nozzle plate, with a specific nozzle arrangement and a collection surface. Sample-laden air is drawn into the impactor and passes sequentially through the stages; nozzle size and total nozzle area decrease with stage number. Volumetric air flow rate through the system is constant; so as nozzle area decreases, air and particle velocities increase. As a result, smaller and smaller particles acquire sufficient inertia to impact on the collection surface rather than remaining entrained in the air stream (Figure 1). Therefore, for a given flow rate, each stage of the impactor is associated with a cut-off diameter, a figure that defines the size of the particles retained on that collection surface; any residual material is captured by a Micro-Orifice Collector (MOC) or glass fiber filter. Analyzing these size fractions, typically by high pressure liquid chromatography (HPLC), produces APSD data for the active. This simple outline raises some of the key issues relating to cascade impactor use: