Evaluation of the Respimat Soft Mist Inhaler using a Concurrent CFD and In Vitro Approach

Background: The Respimat Soft Mist Inhaler is reported to generate an aerosol with low spray momentum and a small droplet size. However, the transport characteristics of the Respimat aerosol are not well understood. The objective of this study was to characterize the transport and deposition of an aerosol emitted from the Respimat inhaler using a combination of computational fluid dynamics (CFD) modeling and in vitro experiments. Methods: Deposition of the Respimat aerosol was assessed in the inhaler mouthpiece (MP), a standard induction port (IP), and a more realistic mouth-throat (MT) geometry at an inhalation flow rate of 30 L/min. Aerosols were generated using an albuterol sulfate (0.6%) solution, and the drug deposition was quantified using both in vitro experiments and a CFD model of the Respimat inhaler. Laser diffraction experiments were used to determine the initial polydisperse aerosol size distribution. Results and Conclusions: It was found that the aerosol generated from the highly complex process of jet collision and breakup could be approximated in the model using effective spray conditions. Computational predictions of deposition fractions agreed well with in vitro results for both the IP (within 20% error) and MT (within 10% error) geometries. The experimental results indicated that the deposition fraction of drug in the MP ranged from 27 to 29% and accounted for a majority of total drug loss. Based on the CFD solution, high MP deposition was due to a recirculating flow pattern that surrounded the aerosol spray and entrained a significant number of small droplets. In contrast, deposition of the Respimat aerosol in both the IP (4.2%) and MT (7.4%) geometries was relatively low. Results of this study indicate that modifications to the current Respimat MP and control of specific patient variables may significantly reduce deposition in the device and may decrease high oropharyngeal drug loss observed in vivo.