Mutual inhibition of the insulin absorption-enhancing properties of dodecylmaltoside and dimethyl-beta-cyclodextrin following nasal administration.

Abstract

To determine if a nasal insulin formulation containing two distinct absorption-enhancing agents exhibits an additive or synergistic increase in the rate of systemic insulin absorption. The pharmacokinetics and pharmacodynamics of insulin absorption were measured in hyperglycemic anesthetized rats following nasal insulin administration with formulations containing two different types of absorption-promoting agents, dimethyl-beta-cyclodextrin (DMBCD) and dodecylmaltoside (DDM). When either DDM (0.1-0.5%) or DMBCD (1.0-5.0%) was added to the nasal insulin formulation, a significant and rapid increase in plasma insulin levels was observed, with a concomitant decrease in blood glucose concentration. A combined preparation containing 0.25% DDM (0.005 M) and 2.5% DMBCD (0.019M), however, failed to cause an increase in plasma insulin levels or a decrease in blood glucose concentration. Increasing concentrations of DDM added to an insulin formulation with a fixed DMBCD concentration caused a decrease, rather than an increase, in systemic absorption of insulin. Mixing DMBCD and DDM resulted in mutual inhibition of their ability to enhance systemic absorption of insulin following nasal delivery. The results are consistent with the formation of an inclusion complex between DDM and DMBCD which lacks the ability to enhance nasal insulin absorption.