Enteric coated insulin pellets: development, drug release and in vivo evaluation

Pellets with human insulin as a model drug were prepared by an extrusion and spheronization process to investigate the oral application of peptides. The described process proved suitable for preparing small batches of about 50 g in laboratory scale. The developed formulation was completed by the addition of aprotinin as protease inhibitor and sodium cholate as an intestinal absorption promoter to enhance oral bioavailability of insulin. In order to protect the peptide against the gastric juice the pellets were coated with shellac in a fluid-bed ball coater. Pharmaceutical properties of the produced batches were examined by analysis of contents and dissolution tests. Dissolution of insulin in simulated gastric juice of pH 1.2 was prevented by shellac. On the other hand, a rapid and complete release of the molecular-dispersed insulin from the pellets was found in simulated intestinal fluid (pH 7.5) with simultaneous efficiency of the protease inhibitor against added enzyme activity. Despite promising in vitro results no significant absorption of insulin was detected in vivo after oral application of the pellets to streptozotocin diabetic rats. High sensitivity to enzymatic degradation and low ability to cross the intestinal wall are discussed as limiting factors for the insufficient absorption of insulin in vivo.