Thein vitroandin vivoinvestigation of a novel small chamber dry powder inhalation delivery system for preclinical dosing to rats

Abstract

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.

Selective Nonsteroidal Glucocorticoid Receptor Modulators for the Inhaled Treatment of Pulmonary Diseases

“…Having demonstrated satisfactory plasma pharmacokinetics, the inhalation properties of 1b were investigated in advanced dry powder inhalation systems, which allow for pulmonary particle distribution by active breathing. 20 A delayed distribution into the systemic circulation is desirable to prolong the pulmonary residence time of the drug to favor local over systemic effects. 10a,d,21 In our hands, the mean retention times (MRT) in rat lung for established ICS were found to be 0.74 and 6.5 h for 2 and 3, respectively.…”