Influence of multiple nasal administrations of bioadhesive powders on the insulin bioavailability

Peptides and more especially insulin are mainly used in therapies that need multiple drug administration. As peptides are highly potent, it is required that their bioavailability remains constant even during a long term administration. In this study, the bioavailability and blood glucose levels are reported after multiple nasal administration of insulin via two bioadhesive platforms consisting of a cospray dried mixture of Amioca((R)) starch and Carbopol((R)) 974P (1/3) and a physical mixture of drum dried waxy maize starch and Carbopol((R)) 974P (9/1), respectively. The experiments were performed in rabbits and the formulations were administered during 8 consecutive days. The bioavailability and the maximal decrease of the blood glucose level were determined on the first and last day of the insulin administration. These two parameters were decreased on the eighth day compared with the first day of administration. When the formulations were not administered from day 2 until day 7, the bioavailability on the eighth day compared with the first day of administration was not modified. It was concluded that daily administrations of the bioadhesive formulations affected the nasal bioavailability of insulin in rabbits. (C) 2002 Elsevier Science B.V. All rights reserved.