Buccal absorption of insulin in the dog.

Insulin was buccally administered to beagle dogs in the form of a solution using a specially designed buccal cell, or in the form of films (buccal flats). 0.5 ml solutions of different pH (3, 4, 5, 6, 7.5) or of pH 7.5 in combination with sorption promoters (sodium taurocholate, dextran sulfate, linoleic acid, TranscutolR, LabrafilR M 1944 CS, urea and AzoneR) were administered for 0.5 h to anesthetized dogs. Buccal flats 1 X 2 cm in size. All dosage forms contained 10 IU of human insulin. The control solution (normal saline) and the solution of pH 5 resulted in the least pharmacologic availability, P.A. (ratio of area under % glucose reduction X time curve buccally to I.V.). Values of 0.9 % and 1.8%, respectively, were calculated. The insulin solution of pH 7.5 gave the highest P.A. The addition of sorption promoters to the pH 7.5 solution did not further increase the P.A. The combination of pH 7.5 - LabrafilR - AzoneR showed the least SD for the P.A., i.e. 18.3% +/- 4.7. The highest reduction in glucose concentration was found after administration of the taurocholate-linoleic acid combination Cmax = 57.2% +/- 6.3. The buccal flats reached a Cmax of about 16% +/- (SD) and a P.A of about 15% +/- (SD).