Novel oral microspheres of insulin with protease inhibitor protecting from enzymatic degradation

Abstract

Eudragit L100 insulin microspheres (IMS) containing a protease inhibitor were prepared for an oral dosage form of insulin. The efficiencies of insulin incorporation of IMS containing trypsin inhibitor (TI), chymostatin (CS), Bowman-Birk inhibitor (BBI) and aprotinin (AP) amounted to approx. 80% and did not differ among the preparations. In a release study, the more than 90% of insulin remaining after treatment of simulated gastric fluid was released in a medium of simulated intestinal fluid during the initial 60 min. The protective efficiency of the various preparations toward three digestive enzymes (pepsin, trypsin and α-chymotrypsin) was investigated under the chosen experimental conditions. Strong insulin protective efficiency towards pepsinic degradation was observed in all preparations. The highest efficiencies towards each trypsinic and α-chymotrypsinic degradation were achieved with IMS containing TI and IMS containing CS, respectively. IMS containing AP was less resistant to trypsinic and α-chymotrypsinic degradation compared with IMS containing TI towards trypsin and IMS containing CS towards α-chymotrypsin, but was slightly more effective than IMS containing BBI towards both enzymes. On the other hand, complete insulin degradation after respective enzymatic incubation was observed in IMS without inhibitor. These results indicated that IMS containing protease inhibitor could be prepared and would be able to protect insulin from proteolytic degradation.