Preliminary In Vivo Evaluation of an Oral Multiple-Unit Formulation for Colonic Delivery of Insulin

A multiple-unit formulation for time-dependent colonic release of insulin was prepared and evaluated. The system comprised a minitablet core containing the protein and a permeation enhancer, an internal swellable/erodible layer based on low-viscosity hydroxypropyl methylcellulose (HPMC), an intermediate Eudragit®NE film including a superdisintegrant (sodium starch glycolate), able to slow down water penetration into the underlying functional layer, and an outermost enteric coat intended to overcome the issue of variable gastric residence. When this system was administered to diabetic rats, a peak in insulin plasma concentrations was observed 6 h post-dose along with a drop in glycaemia. Both could coincide, based on rat gastrointestinal transit times, with the system being positioned in the ileo-colonic region.