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 intestine. There have been a number of basic studies in which peptide solutions were administered to experimental animals via the lungs. Although there have been several studies of pulmonary peptide absorption from dry powder formulations, 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 administration. Dry powders of fluorescein (FL) and FITC-dextran (FD4) were manufactured by the spray-drying technique. The effects of operating conditions on 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 time was extended, suggesting that dissolution was the rate-determining step for FL absorption from dry powder. For FD4, the rate of absorption may not be regulated by dissolution but by epithelial transport. Absorption of insulin from spray-dried powder via the rat trachea was investigated using this apparatus. Intratracheally administered spray-dried insulin powder decreased plasma glucose level to a greater extent than spray-dried insulin solution administered via the same route. Thus, the apparatus is simple, inexpensive, and useful for rapid screening of dry powder formulations.
Okamoto
H
H
Faculty of Pharmacy, Meijo University, 150 Yagotoyama Tempaku-ku, Nagoya 468-8503, Japan. okamotoh@meijo-u.ac.jp
Aoki
M
M
Danjo
K
K
D000042:Absorption; D000818:Animals; D019540:Area Under Curve; D001786:Blood Glucose / Q000032:analysis; D002626:Chemistry, Pharmaceutical; D003911:Dextrans / Q000493:pharmacokinetics; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D007328:Insulin / Q000008:administration & dosage; D008168:Lung / Q000378:metabolism*; D008297:Male; D011208:Powders; D051381:Rats; D017207:Rats, Sprague-Dawley; D014132:Trachea / Q000378:metabolism*
D001786:Blood Glucose; D003911:Dextrans; D007328:Insulin; D011208:Powders; C015219:fluorescein isothiocyanate dextran; D016650:Fluorescein-5-isothiocyanate