Comparison of optical particle sizing and cascade impaction for measuring the particle size of a suspension metered dose inhaler

摘要

Optical techniques for the particle size characterization of metered dose inhaler (MDI) suspensions have been developed as an alternative to the labor-intensive and time-consuming impaction method. In this study, a laser diffraction (LD) apparatus with a liquid cell ("wet cell" method) and a "time-of-flight" apparatus named aerodynamic particle sizer (APS) were utilized to assess MDI suspensions with varied formulation compositions and storage conditions. The results were compared with the conventional Anderson cascade impaction (ACI) data. The two optical methods were able to detect the changes in particle size distributions between formulations, yet to a lesser extent than those observed using the cascade impaction methodology. The median aerodynamic particle size measured by the APS method and the median geometric particle size obtained from the LD method were linearly correlated with the corresponding ACI results in the range of 2-5 mu m. It was also found that the APS measurement was biased towards the finer particle size region and resulted in overestimated fine particle fraction (FPF) values which were 2-3 times folds of the ACI results. In conclusion, the optical particle sizing techniques may, under some circumstances, be viable techniques for the rapid assessment of MDI suspensions. The "wet cell" LD method, in particular, is found to be a valuable means of detecting active pharmaceutical ingredient (API) particle size changes in an MDI suspension. Using both the LD and the APS methods in early formulation screening followed by a final assessment with cascade impaction analysis can improve the efficiency of MDI formulation development.