Biopharmaceutic aspects of buccal absorption of insulin.

Absorption of insulin through buccal mucosa was investigated using rabbits as animal model. The effects of various dose sizes, pH of the insulin solutions and a series of sorption enhancers or absorption promoters on the hypoglycemic response were studied using a buccal cell. In the absence of sorption promoters, the various dose sizes and pH of the administered insulin solution did not show any significant hypoglycemic response, indicating that substantial amounts of insulin were not absorbed through the buccal mucosa. In the presence of sorption enhancers, the extent of hypoglycemia was significantly enhanced in terms of AUC and Cmax. Among the sorption enhancers investigated, Brij 35 was the most satisfactory one, followed by sodium taurocholate, sodium laurylsulfate, sodium deoxycholate, sodium methoxysalicylate, sodium dextransulfate and EDTA. An inverse correlation was found between extent of hypoglycemia and light scattering intensity of insulin solution. The extent of hypoglycemia in presence of Brij 35 was concentration-dependent although a plateau was observed at high concentration range. The maximum pharmacological availability obtained from buccal administration of insulin solution was about 12%, while that obtained with the tablet formulation was about 4.3%.