Summary

Aims and Methods. Given the evolving understanding of in vitro/in vivo relationships for aerosol drug delivery and the demand for clinically relevant model tests, we evaluated the drug delivery from orally inhaled aerosol devices using an in vitro model with a pMDI (5x 100 µg salbutamol) and a Vibrating Mesh nebulizer (VM; 500 µg salbutamol) incorporating three distinct mouth- throat (M-T) inlet models (United States Pharmacopeia Inlet – USP, Alberta Idealized Throat – AIT, and McMaster 3D printed Oropharynx – 3DOR). Furthermore, we evaluated the regional drug deposition over the three compartments of the 3DOR (mouth, pharynx, and trachea). All measurements were performed using a fixed Breath Simulator adult breathing pattern Results and conclusion: The pMDI aerosol presented similar deposition between all three M-T inlets, and at the inspiratory filter as well. Whereas, when the VM nebulizer was used, a lower inlet deposition was seeing in the USP, compared to both 3DOR and AIT (µg; p=0.001, CI95% -73.8 to -10.6; p=0.006, CI95% -79.9 to -16.6, respectively). The amount of drug collected on the inspiratory filter was significantly higher with the USP, compared to AIT (µg, CI95% 2.5 to 65.8, p=0.03), and to 3DOR (µg, CI95%14.2 to 77.5, p=0.002). The tri-compartmental analysis of 3DOR presented a significant difference in distribution of aerosol when the pMDI was used compared to the vibrating MESH nebulizer, with major aerosol deposition (77%) at the mouth, whereas the VM presented a homogenous distribution between the three compartments. The inhalation devices presented distinct partitioning deposition throughout the inlet models, based on their characteristics. 

Key Message

In vitro outcomes may vary with the M-T inlet used to introduce the aerosol from the delivery system to the model components. In this regard, models need to differentiate between those for QC and those that provide information on in vivo drug delivery.