Using computational fluid dynamics to estimate the efficiency of delivery by changing the position of the rat snout and airflow received using an inhalation directed flow chamber

SOT 2025 -- Inhalation administration is a common dose route used in nonclinical development for delivering drugs to the lungs. The standard approach is to evaluate drug safety in both a rodent and non-rodent species. With the continued use of both New Chemical Entities (NCEs) and biopharmaceuticals, rats continue to be the rodent species of choice. The standard method for delivering the aerosol to rats is using a snout-only inhalation chamber called a direct flow chamber. During the exposure period, the rats are restrained in plastic clear restraint tubes. Consistent dosing is pivotal in ensuring effective study conduct and data interpretation to draw accurate conclusions about the safety of the test article; however, it is commonly observed that the animal and animal snout frequently move during the dosing period and require adjustment where possible. Furthermore, there is anecdotal evidence that the animal-to-animal variation with the dose received is greater for the inhalation route of administration compared to other routes such as oral and intravenous. In this study, Labcorp wanted to establish whether the position of the snout relative to the end of the aerosol chamber delivery tube contributed towards this perceived animal-to-animal dose variability.