Development of novel efficient rodent nose-only inhalation exposure systems

Mikael Brülls

It was decided within AstraZeneca R&D to develop novel efficient passive nose-only inhalation exposure systems to enable inhalation administration to rodents in early preclinical development phase. It was decided from the start, when a first novel inhalation system was developed, that it would be a nose-only inhalation exposure system to be used with commercially available restraining tubes. The most important design feature of the novel inhalation exposure system was to develop a closed exposure chamber instead of a flow-pass system in order to improve the utilization of the drug compound. The limited amount of test material available in this early development phase together with practical limitations regarding time and resources for formulation development precluded the possibility to use dry powder aerosols and nebulization was therefore selected as the aerosol generation technique for the novel inhalation exposure system. It was decided to use a vibrating mesh nebulizer with the first novel exposure system. The in-vitro investigations made with a first real prototype system was successful and it was therefore decided to manufacture two fully equipped exposure units for in-vivo use. The first novel inhalation system did unfortunately not meet the expected improvement in utilization of drug compound in in-vivo use. Two other new novel inhalation systems were therefore developed at AstraZeneca R&D. The two new systems have been shown to be significantly more efficient than the first system and also proven to be able to replace intratracheal instillation in the early development phase at AstraZeneca R&D.

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