Oil-based formulations for oral delivery of insulin

Several oil‐based solution formulations of insulin were prepared, in which insulin was solubilized in the form of anhydrous reverse micelles. The preparation process involved micellar dissolution of insulin followed by freeze drying, then reconstitution of lyophilized product with an oil phase. These formulations were stable at room temperature for up to 12 months. No significant changes in the appearance were observed and no degradation products of insulin were detected during the course of the stability study. The efficacy of these formulations was evaluated in‐vivo using diabetic Wistar rat as an animal model and then a specific formulation was chosen for further study in non‐diabetic New Zealand rabbits. It was found that the efficacy of insulin oil solution was dose dependent and insulin oil solution had the same efficacy as insulin emulsion with the same formulation composition. If ethylene‐diaminetetraacetic acid (EDTA) was pre‐delivered 40 min before the delivery of insulin oil solution, the hypoglycaemic effect of insulin oil solution was greatly enhanced, with an AUC (% glucose reduced) value increase from 28.5 ± 14.7 to 167.1 ± 72.3. The improvement of oral absorption induced by pre‐delivery of EDTA might be attributed to enzyme inhibition, reduced gut mobility and the opening of paracellular routes.