In vitro and in vivo evaluation of insulin microspheres containing protease inhibitor

The aim of this study was to investigate the applicability of microspheres containing protease inhibitor for oral delivery of insulin (CAS 9004-10-8). Microspheres of insulin were prepared by water-in-oil-in-oil (w/o1/o2) double emulsion solvent evaporation method. Formulations with different drug/polymer ratios were prepared and characterized by drug loading, loading efficiency, yield, particle size, scanning electron microscopy (SEM), Fourier Transform Infrared spectroscopy (FTIR). The in vitro release studies were performed in pH 1.2 and 7.4. In vivo studies on rats were conducted in order to investigate the bioavailability and performance of oral microspheres. The best polymer to drug ratio in microspheres was 15.6:1 (F2 formulation). The loading efficiency was 77.36%, production yield was 54.55% and mean particle size was 222.4 microm. SEM studies showed that the microspheres were spherical and porous in nature. Data obtained from in vitro release were fitted to various kinetic models and high correlation was obtained in the first order model. The results of enzymatic degradation indicated that insulin could be protected from trypsinic degradation in the microspheres. Our results indicate that the microspheres containing aprotinin (CAS 9087-70-1) have the advantage of high loading efficiency, pH responsive and prolonged release carrying insulin to the optimum site of absorption as well as the enhanced insulin absorption and biological response.