Pulmonary delivery of salmon calcitonin dry powders containing absorption enhancers in rats.
OBJECTIVE
To evaluate the effects of absorption enhancers in dry powders and in liquids, pulmonary absorption of salmon calcitonin (sCT) in various formulations was measured.


METHODS
The dry powder of sCT was prepared by a freeze-drying method with a jet mill. After intratracheal administration of sCT dry powder and liquid (solution) preparations to rats, plasma sCT levels and calcium levels were measured.


RESULTS
After intratracheal administration without absorption enhancers, sCT in the dry powder and in the liquid were absorbed nearly to the same degree. Absorption enhancers (oleic acid, lecithin, citric acid, taurocholic acid, dimethyl-beta-cyclodextrin, octyl-beta-D-glucoside) were much more effective in the dry powder than in the solution. The reason may be that the enhancers added to the dry powder dissolved at high concentrations in a trace volume of the fluid lining the alveolar epithelium.


CONCLUSIONS
The present results suggest that the pulmonary absorption of peptides and proteins can be greatly improved by formulating them into dry powders with smaller amounts of enhancers than in liquid dosage forms.
Kobayashi
S
S
Pharma Research and Development Division, Hoechst Japan Limited, Saitama, Japan.
Kondo
S
S
Juni
K
K
D000042:Absorption; D000818:Animals; D002116:Calcitonin / Q000097:blood / Q000493:pharmacokinetics*; D003911:Dextrans; D004357:Drug Synergism; D005069:Evaluation Studies as Topic; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives; D007442:Intubation, Intratracheal; D008168:Lung / Q000378:metabolism*; D008297:Male; D011208:Powders; D011650:Pulmonary Alveoli / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012996:Solutions
D003911:Dextrans; D011208:Powders; D012996:Solutions; C015219:fluorescein isothiocyanate dextran; C028815:salmon calcitonin; D002116:Calcitonin; D016650:Fluorescein-5-isothiocyanate