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 (DMbetaCD) as an absorption enhancer in rabbits was studied. The nasal administration of insulin/DMbetaCD 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 DMbetaCD 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/DMbetaCD solutions. On the other hand, nasal administration of the lyophilized insulin/DMbetaCD 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/DMbetaCD powder was 13 +/- 4%, compared to 1 +/- 1% for both an insulin/DMbetaCD liquid and an insulin/lactose powder formulation. It is concluded that insulin powder formulations with DMbetaCD as an absorption enhancer are much more effective than liquid formulations.