Evaluation of a new Aerodynamic Particle Sizer Spectrometer for size distribution measurements of solution metered dose inhalers.

The ability of the Model 3320 and newer Model 3321 Aerodynamic Particle Sizer Spectrometer (APS) to make accurate mass-weighted size distribution measurements of solution metered dose inhalers (MDIs) was evaluated. Measurements of experimental HFA-134a beclomethasone dipropionate MDIs were made with both the APS 3320 and APS 3321 and compared to the Andersen Cascade Impactor (ACI). The mass-weighted size distribution measurements from the ACI and APS 3321 agreed well but were very different than the APS 3320 measurements. Evaluation of the APS 3320 size distribution measurements indicated that the presence of a few erroneous particle measurements caused a gross overestimation of the mass median aerodynamic diameter (MMAD) and geometric standard deviation (GSD). When a previously described technique was used to eliminate erroneous particle size measurements from the size distribution calculation, the MMAD and GSD from the APS 3320 agreed well with those from the ACI and APS 3321. The GSD from the APS 3321 and the APS 3320 after a mask was applied were slightly larger than from the ACI. It is believed that both APS instruments slightly underestimate the GSD while the ACI slightly overestimates the GSD. Further experiments were conducted using the APS 3321 to examine the influence of drug concentration and cosolvent level on the size distribution of solution formulation MDIs. The MMAD was shown experimentally and theoretically to be proportional to drug concentration to the one-third power. Cosolvent concentration had minimal influence on MMAD over the range examined. The measurements reported in this paper demonstrate that it is possible to obtain accurate mass-weighted size distribution measurements with the APS 3320 and APS 3321. These instruments allow for accurate size distribution measurements to be made in minutes as opposed to the hours required to conduct and analyze size distribution measurements from cascade impactors.