Targeted enteral delivery of insulin to rats

The aim of the present work was to investigate the effectiveness of a dosage form approach for monitoring both the inactivation and the absorption processes by targeting insulin delivery to the colon. The dosage form design is based on incorporating insulin into small, soft gelatin capsules coated with polyacrylic polymer (Eudragit) having pH-dependent properties. The capsules were filled with 100 mg of the following formulation: 8 units (u) porcine insulin and 20 mg of surfactant mixture (sodium laurate: cetyl alcohol 2 : 8) in arachis oil, and were coated with mixtures of various ratios of Eudragit RS, L and S. The in vitro pH-dependent release rates of coated capsules were tested by scintillation counting using [¹²⁵I]insulin and two formulations which released the drug the most between pHs 7.5 and 8.0 (RS1 and RS2) were chosen for further studies in rats. Insulin absorption was measured by its hypoglycemic effect. Blood glucose concentrations were determined at 610 nm using the GOD-Perid method. The oral administration of the two chosen insulin-containing formulations gave significant (P<0.01) hypoglycemia when compared with controls. However, the duration, course and the intensity of effect were different for each formulation: the longest effect was obtained with formulation RS1 while the maximum glucose level reduction (up to 45% of initial value) occurred with formulation RS2. It was interesting to observe that the preadministration of a surfactant capsule did not change the glycemic profile; however, its post-administration prolonged the effect of RS2 by one hour.