Evaluation of starch-maltodextrin-Carbopol® 974 P mixtures for the nasal delivery of insulin in rabbits

In this study insulin was administered nasally to rabbits as a dry powder formulation. The powders consisted of drum-dried waxy maize starch (DDWM) or maltodextrins with different DE values and Carbopol(R) 974 P. The powders were prepared by freeze-drying a dispersion of these excipients with insulin. Bioavailabilities obtained with the powder formulations containing DDWM/Carbopol(R) 974 P (5 and 10%) were significantly higher (p<0.05) than those containing maltodextrins-Carbopol(R) 974 P mixtures. The bioavailability of the powder formulation containing DDWM and 10% Carbopol(R) 974 P was significantly higher (14.4%) than the bioavailability of the same mixture containing 5% Carbopol(R) 974 P (9.9%). The bioavailability, t(max) and C-max values of the formulation with 5% Carbopol(R) 974 P were significantly higher in comparison with the formulation without Carbopol(R) 974 P. 10% Carbopol(R) 974 P was required when maltodextrins were used in order to obtain a significantly higher bioavailability compared with the formulations without Carbopol(R) 974 P. Freeze-drying seemed a prerequisite for a good bioavailability From the powder formulation as well as the ratio of insulin versus bioadhesive powder (1 IU and 2 IU/mg of bioadhesive powder). (C) 2000 Elsevier Science B.V. All rights reserved.