The in vitro and in vivo investigation of a novel small chamber dry powder inhalation delivery system for preclinical dosing to rats

Abstract

Purpose: This research describes a novel “minitower” dry powder delivery system for nose-only delivery of dry powder aerosols to spontaneously breathing rats.

Methods: The minitower system forces pressurized air through pre-filled capsules to deliver aerosolized drug to four nose ports; three of which house spontaneously breathing rats, with the fourth used as a control. Within each port are vent filters which capture drug that was not inhaled for further quantitation. These vent filters along with a novel control system referred to as the “artificial rat lung”, allow for the theoretical amount of drug delivered and subsequently inhaled by each rat to be calculated.

Results: In vitro and in vivo studies have demonstrated this system’s ability to deliver aerosolized drug to rats. The in vitro study showed that ～30% of the starting dose reached the 4 ports and was available for inhalation. During in-vivo studies, rats inhaled ～34% of the delivered dose. Of the estimated inhaled dose, 12–18% was detectable in the various tissue samples, with over 30% of the recovered dose found in the rat’s lungs.

Conclusion: Results show that this system is capable of reproducibly delivering drug to the lungs of spontaneously breathing rats. Advantages over current delivery methods include being amenable to the administration of multiple doses and using less (milligram) amount of starting material. In addition, this technique avoids anesthesia which is typically required for instillation or insufflation, and thus has the potential as an efficient and noninvasive aerosol delivery method for preclinical drug development.