Nasal insulin delivery with dimethyl-beta-cyclodextrin as an absorption enhancer in rabbits: powder more effective than liquid formulations.
The nasal absorption of insulin using dimethyl-beta-cyclodextrin (DM beta CD) as an absorption enhancer in rabbits was studied. The nasal administration of insulin/DM beta CD liquid formulations did not result in significant changes in serum insulin and blood glucose concentrations. In contrast, previous experiments in rats showed that the addition of DM beta CD to the liquid nasal formulation resulted in an almost-complete insulin absorption, with a concomitant strong hypoglycaemic response. Apparently, the effect of the cyclodextrin derivative on insulin absorption differs between animal species following nasal delivery of insulin/DM beta CD solutions. On the other hand, nasal administration of the lyophilized insulin/DM beta CD powder dosage form in rabbits resulted in increased serum insulin concentrations, and a maximum decrease in blood glucose of about 50%. The absolute bioavailability of the nasally administered insulin/DM beta CD powder was 13 +/- 4%, compared to 1 +/- 1% for both an insulin/DM beta CD liquid and an insulin/lactose powder formulation. It is concluded that insulin powder formulations with DM beta CD as an absorption enhancer are much more effective than liquid formulations.
Schipper
N G
NG
Center for Bio-Pharmaceutical Sciences, Leiden University, The Netherlands.
Romeijn
S G
SG
Verhoef
J C
JC
Merkus
F W
FW
D000042:Absorption; D000281:Administration, Intranasal; D000704:Analysis of Variance; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002626:Chemistry, Pharmaceutical; D003505:Cyclodextrins; D004304:Dosage Forms; D005260:Female; D007328:Insulin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011208:Powders; D011817:Rabbits; D047392:beta-Cyclodextrins
D001786:Blood Glucose; D003505:Cyclodextrins; D004304:Dosage Forms; D007328:Insulin; D011208:Powders; D047392:beta-Cyclodextrins; C038119:heptakis(2,6-O-dimethyl)beta-cyclodextrin