Enhanced Absorption of Insulin and (Asu1,7)Eel‐Calcitonin using Novel Azopolymer‐Coated Pellets for Colon‐Specific Drug Delivery

Abstract

The objective of this study was to estimate colon‐specific delivery of insulin and (Asu1,7)eel‐calcitonin using novel azopolymer‐coated pellets. In vitro drug‐release experiments from the azopolymer‐coated pellets containing fluorescein isothiocyanate dextran (MW 4400; FD‐4) were carried out by the Japanese Pharmacopoeia (J.P.) XIII rotating basket method with some slight modifications. Little release of FD‐4 from the pellets was observed in phosphate buffered saline. However, the release of FD‐4 was markedly increased in the presence of rat cecal contents. The intestinal absorption of insulin and (Asu1,7)eel‐calcitonin after oral administration of the azopolymer‐coated pellets containing these peptides with camostat mesilate was evaluated by measuring the hypoglycemic and hypocalcemic effects, respectively. A slight decrease in plasma glucose levels was observed following the oral administration of these pellets containing 12.5 IU of insulin compared with the same dose of insulin solution. Camostat mesilate, a protease inhibitor that is incorporated with insulin in these pellets, further decreased the plasma glucose levels in a dose‐dependent manner. Similar results were also obtained with the oral administration of pellets containing (Asu1,7)eel‐calcitonin. These findings suggest that azopolymer‐coated pellets may be useful carriers for the colon‐specific delivery of peptides including insulin and (Asu1,7)eel‐calcitonin. © 2001 Wiley‐Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 90:89–97, 2001