Formulating insulin for oral administration:: Preparation of hyaluronan-insulin complex

Purpose. To investigate the behaviour of peptides and hyaluronan in strong acid solutions containing electrolytes in the preparation of a new formulation of insulin, hyaluronan-insulin complex, and to evaluate the in vivo oral activity of the formulation. Methods. Individual processing parameters in the preparation of the insulin complex were first refined, and two formulations were subsequently investigated. The chemical structure, particle size and hydrophilic/hydrophobic properties of the insulin complex in these formulations were studied using light scattering techniques, amino acid analysis, atomic force microscopy and cryo-transmission electron microscopy. The in vivo activity of oral hyaluronan-insulin complex was then evaluated by measuring the decrease in blood glucose concentrations in streptozotocin diabetic rats. Results. Five of seven batches of the two insulin complex formulations fit the baseline criteria for approval of the new formulation. The formulation consists of a transparent aqua sol containing a solid hydrophobic phase as precipitate. Glucose-lowering activity was demonstrated after oral administration of the insulin complex to diabetic rats. Conclusion. A new insulin formulation, a hyaluronan-insulin complex, has been developed and oral activity has been demonstrated.