Use of the Next Generation Pharmaceutical Impactor for Particle Size Distribution Measurements of Live Viral Aerosol Vaccines

Abstract

Aerosol administration of live measles vaccine virus has proven to be extremely efficacious in field trials using an industrial compressor coupled to a disposable nebulizer (IPI). To develop a new system for administration, it is necessary to characterize the operating characteristics of the old system. There are no standardized techniques for measuring particle size of live biological agents. This study evaluated the Next Generation Pharmaceutical Impactor's (NGI) ability to particle size wet aerosols in an effort to measure the particle size distribution of live measles vaccine from the IPI nebulizer. As a control albuterol was aerosolized using a Pari LC Star, since the soluble albuterol is evenly distributed throughout the droplets and laser diffraction measurements should agree with those from the NGI, as long as the NGI is cooled to prevent heat transfer to the aerosol. Albuterol was also used as a control for the IPI using quantitative ultraviolet spectrophotometry. There was close agreement in MMD (mean +/- 95% CI) for the LC Star, measured by laser diffraction (3.24 +/- 0.06 microm) and the NGI (2.93 +/- 0.22 microm) and the IPI (4.26 +/- 0.17 and 4.26 +/- 0.24 microm, respectively). For the measles vaccine assayed for plaque forming units, there were significant differences between the NGI MMD (6.14 +/- 0.39 microm) compared to laser diffraction (4.95 +/- 0.16 microm) indicating that the vaccine is not evenly distributed among the droplets of various sizes. This is likely clumping of the virus due to gelatin in the formulation. These data indicate that the NGI is capable of particle sizing live biological agents.