Experimental and Theoretical Investigation of a New Approach to In-Use Impactor Quality Specifications

Experimental and Theoretical Investigation of a New Approach to In-Use Impactor Quality Specifications

Daryl L. Roberts¹, Mårten Svensson², Karolina Sandell², Dennis Sandell³

¹Applied Particle Principles LLC, 17347 Westham Estates Court, Hamilton, VA 20158, USA

²Emmace Consulting AB, Medicon Village, S-223 81, Lund, Sweden

³S5 Consulting, Ekvägen 8, S-275 62, Blentarp, Sweden

Summary

The behavior of cascade impactors has been studied under non-ideal nozzle conditions, including those that can arise in practical laboratory use.  This study is a first step towards establishing a new method of setting specifications on used impactor nozzle dimensions, one that is derived from the drug product’s mass-per-stage specifications established, for example, at the time of regulatory approval, rather than on the original as-manufactured nozzle dimensions.  Next Generation Impactors (NGIs) were tested with purposely occluded nozzles with a commercial beclomethasone dipropionate (BDP) metered-dose inhaler (MDI), measuring the collected drug mass and the pressure drop across stages with ordinary (unblocked) and blocked nozzles and noting changes in these quantities.

The pressure drop across unblocked stages varied with flow rate in accord with theory, as did the pressure drop across any given stage when nozzles were increasingly blocked at a fixed flow rate.  To quantify the change in collected particle mass when nozzles were blocked, this study focused on NGI stage 5 at an inlet flow rate of 30 L/min.  The collected drug mass on stage 5 increased with increasing proportion of blocked nozzles, but generally less than expected from a first-order model, possibly because of shifts in the individual nozzle behavior, especially when > 10% of the nozzles were blocked.  Nevertheless, this model enables an approach to impactor quality that is independent of as-manufactured nozzle dimensions and that can rely upon stage pressure drop values.  The overall approach rests firmly on known impaction principles and is worth further development.