A novel apparatus for rat in vivo evaluation of dry powder formulations for pulmonary administration

The lungs have attracted increasing attention as a site for administration of drugs, including macromolecules that are poorly absorbed from the intest ine. There have been a number of basic studies in which peptide solutions w ere administered to experimental animals via the lungs. Although there have been several studies of pulmonary peptide absorption from dry powder formu lations, a simpler and more inexpensive apparatus for administration of dry powders would enhance rapid screening of the formulations. In this study, we developed a simple apparatus to disperse dry powders. The apparatus has two 3-way stopcocks; one allows dispersal of powders at a constant pressure and airflow, and the other allows rats to breathe before and after adminis tration. Dry powders of fluorescein (FL) and FITC-dextran (FD4) were manufa ctured by the spray-drying technique. The effects of operating conditions o n the absorption of these model drugs were examined in rats. The C-max for FL from dry powder was lower than that from solution and mean residence tim e was extended, suggesting that dissolution was the rate-determining step f or FL absorption from dry powder. For FD4, the rate of absorption may not b e regulated by dissolution but by epithelial transport. Absorption of insul in from spray-dried powder via the rat trachea was investigated using this apparatus. Intratracheally administered spray-dried insulin powder decrease d plasma glucose level to a greater extent than spray-dried insulin solutio n administered via the same route. Thus, the apparatus is simple, inexpensi ve, and useful for rapid screening of dry powder formulations. (C) 2000 Wil ey-Liss, Inc. and the American Pharmaceutical Association.