Calibration of the modified Electrical Low-Pressure Impactor (ELPI) for use with pressurized pharmaceutical aerosols

The modified Electrical Low Pressure Impactor (ELPI) is currently being used in several laboratories to determine inherent electrostatic charge of pharmaceutical aerosols as a function of their particle size. However, the ELPI appears to underestimate the aerodynamic particle size distributions (aPSDs) of pressurized metered dose inhalers (pMDIs), casting doubt upon the manufacturer's calibration. In the present study, four commercially available pMDIs with a range of aPSDs were used to recalibrate cutoff diameters (d50s) of the ELPI stages using a reference ACI. Particle size analyses were performed in a mensurated ACI and a calibrated modified ELPI (n = 5); stage coating was employed in both instruments. The ACI data were fitted to a lognormal cumulative distribution function by nonlinear regression analysis. Best estimates for mass median aerodynamic diameter (MMAD) and geometric standard deviation (GSD) for each pMDI were obtained and used in combination with impaction results from the modified ELPI to determine new d50s for each of the ELPI stages by numerical methods. Ventolin HFA was employed to validate the new ELPI d50 values. The curve-fitting procedure produced excellent fits of the ACI data for all the calibration pMDIs, which were well modeled as mono-modal and lognormally distributed. The mean d50s obtained following recalibration of the modified ELPI were found to deviate increasingly from the manufacturer-supplied values as aerodynamic diameter decreased. Ventolin HFA's MMAD determined using the modified ELPI with the manufacturer-supplied d50s was 2.06 +/- 0.08 microm. The MMAD calculated using the recalibrated d50s was 2.63 +/- 0.09 microm, which was statistically indistinguishable (p = 0.0852) from that determined for Ventolin HFA using the ACI (2.73 +/- 0.09 microm). In the absence of a comprehensive recalibration of the ELPI using monodisperse aerosols, the mean d50s for stages 4-12 of ELPI reported offer a practical way of analyzing the aPSD of pharmaceutical aerosols based on the collection and chemical analysis of ELPI deposition data.