W O/W MULTIPLE EMULSIONS OF INSULIN CONTAINING A PROTEASE INHIBITOR AND AN ABSORPTION ENHANCER - PREPARATION, CHARACTERIZATION AND DETERMINATION OF STABILITY TOWARDS PROTEASES IN-VITRO/

W/O/W multiple emulsions composed of medium-chain triglycerides contai ning insulin with aprotinin, a protease inhibitor, and/or sodium tauro cholate, an absorption enhancer, were prepared by a two-step emulsific ation method at 15 degrees C. Whatever the nature of the substance int roduced in the internal aqueous phase, all the emulsions obtained had very similar properties. The yield of insulin encapsulation, measured by HPLC analysis, was approximately 95%. These systems were stable dur ing at least 3 months of storage at 4-6 degrees C. The main release me chanism was a swelling-breakdown phenomenon after dilution of the emul sions under hypo-osmotic conditions. These emulsions were able to prot ect insulin against enzymatic degradation in vitro. (C) 1997 Elsevier Science B.V.