The NGI Pre-Separator: Designed for Formulations with Large Carrier Particles

BACKGROUND: Compendial methods recommend including a pre-separator (PS) before the multi-stage impactor when testing dry powder inhalers (DPIs) for emitted aerosol aerodynamic particle size distribution (APSD). For data analysis, they are either silent or treat the PS as a "non-sizing" component. The overall message is "use the PS but ignore what it collects." The Next Generation Impactor (NGI) PS reinforces this mindset because it was specifically designed for testing carrier-particle-based DPIs wherein any API in the PS results from a failure to detach from the large carrier particles. However, users with carrier-free DPI formulations might wonder what to do if drug is found in the PS and if it is technically justified to omit this component, thereby increasing laboratory throughput by relying on the NGI alone to provide accurate APSD metrics. METHODS: Particle capture efficiency curves for the NGI PS were constructed from the published calibration data at flow rates of 15, 30, 60, and 100 L/min. These curves and those published for NGI stages 1-7 enabled calculation of how model input aerosols disperse throughout an NGI with or without a PS. APSD metrics were subsequently estimated from these calculated API mass fractions and then compared with and without the PS. RESULTS: The presence of the PS yielded APSD metrics for the model aerosols that were almost indistinguishable from those obtained without the PS, accounting for the API mass recovered from the PS as if it had collected on an impactor stage. CONCLUSIONS: The PS is necessary when and only when the formulation contains large carrier particles. Consequently, for carrier-free formulations, method validation with no PS is likely to succeed. If for any reason it is retained in the test method of a carrier-free formulation, the PS should be treated like an impactor stage for APSD data analysis purposes.