Development of a new aerosol delivery system for systemic pulmonary delivery in anaesthetized and orotracheal intubated rats.
Over the last decade, the systemic absorption of a broad range of therapeutics after pulmonary application has been demonstrated in animals as well as in humans. The most common method used in the laboratory is the intratracheal instillation of drugs in solution. This method is, however, unsatisfactory, because of discrepancies in particle distribution, clearance, kind of injury and bioavailability between instillation and inhalative application. On the other hand, a precise determination of the amount of drug applied by aerosol, and of the aerosol volume retained within the lungs is rather difficult, and is not possible for use with small animals such as mice or rats. We describe a system which allows the delivery of aerosols directly into the animal's lungs, and calculation of the amount of drug retained in the lungs. Our system was tested in vitro and in vivo and was shown to allow precise and efficient pharmacokinetic and toxicological studies to be carried out.
Lizio
R
R
Department of Biopharmaceutics and Pharmaceutical Technology, Saarland University, Saarbruecken, Germany. lizio@crt.hoechst.com
Marx
D
D
Nolte
T
T
Lehr
C M
CM
Sarlikiotis
A W
AW
Borchard
G
G
Jahn
W
W
Klenner
T
T
D000042:Absorption; D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D001682:Biological Availability; D016503:Drug Delivery Systems / Q000662:veterinary*; D007442:Intubation, Intratracheal / Q000379:methods / Q000662:veterinary*; D008168:Lung / Q000187:drug effects*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D000336:Aerosols