Studies On Insulin Oily Formulations For Oral Administration

A new technology to lyophilize in single phase co-solvent system was developed to solubilize water soluble drug in oils, which provide a new potential drug carrier system for administration of proteins and peptides. In this article, this technology was utilized to prepare insulin oily formulations and Insulin self-microemulsifying drug delivery systems(SMEDDS) was successfully developed to improve insulin oral bioavailability.The pretreatments method of Insulin quantitative assay in oily formulation by reversed-phase high performance liquid chromatography was optimized. As a result, the 75% methanol was selected to break the emulsion. The stability of Insulin aqueous solutions with different pH values was inspected under room temperature and this laid grounds to further investigation of the formulation.In this paper, above the ground works of the influential factors that may induce undesirable powder appearance and the opacity of oil solutions, the preparation technology and the formula were both optimized. Several in vitro characteristics of the Insulin oily formulations in aqueous, such as particle size distribution and release of Insulin from the oil phase were investigated and the hypoglycemic effects in normal rats were also evaluated. On the contrary to stomach, Insulin oily formulations can be effectively uptaken through intestinal tracts and the relative oral bioavailability was 4.41%.The in situ loop model in rats was utilized to evaluate the absorption of Insulin formulations in various sites of intestinal tracts and the absorption in ileum was obviously more excellent. Identicaly, the hypoglycemic effects in normal rats after administration of Insulin ARMs through different site of intestinal tracts was investigated. The results of both absorption and hypoglycemia suggested that ileum was the most potent absorption site. The SMEDDS (oil phase45%, surfactants30%, cosurfactants25%) was developed and the serial in vitro characteristics were studied. The diameter of the emulsified solution was 64.0 nm and only 30% of Insulin release after 24 hour’s dialysis. The results of in vitro degradation experiment suggested that SMEDDS can efficiently protect Insulin from enzyme degradation. The hypoglycemic effects in normal rats was studied after the administration of the Insulin SMEDDS was filled into enteric-coated hard gelatin capsules and there was evident dose-dependent effects and the oral relative bioavailability of Insulin ARMs and Insulin SMEDDS were 4.29% and 5.71% respectively.It were concluded that the oily fomulation was able to facilitate Insulin oral absorption and the SMEDDS was much more preferable. But this should be progressively identified in diabetic animal models.