The Influence of Electrostatic Controls on MDI Size Distribution Measurements.

Cascade impactor testing is widely used to characterize the aerodynamic particle-size distribution of metered dose inhaler aerosols. Charge is often imparted to MDI aerosols by triboelectrification as formulation rapidly travels through the valve stem and actuator during atomization. The presence of charge on MDI aerosols can impact the accuracy and reproducibility of APSD measurements made using cascade impactors. The aerodynamic particle size distribution of three different experimental MDI formulations were evaluated using the Next Generation Impactor with and without incorporating static controls during testing. The static controls included grounding the analyst and the equipment, using an ionizing air blower and anti-static gun, rinsing and allowing the actuator to air dry prior to testing, and having the analyst not wear gloves or touch the USP throat during testing. For all three formulations, tests that used static controls had lower actuator and throat deposition and correspondingly higher deposition on the impactor stages. While static controls influenced the amount of drug entering into the impactor during testing, the static controls did not otherwise change the aerodynamic particle size distribution of these particles. Static controls had the greatest impact on the ethanol-free HFA-227 formulation. For this formulation, there was a 15% difference in throat deposition for the tests that did or did not incorporate static controls. These results demonstrated that electrostatic effects can lead to meaningful variability in cascade impactor test results. Static controls should be considered when developing cascade impactor test methods for MDI products in order to eliminate variability in test results.