In Vivo Evaluation of Nanoemulsion Formulations for Metformin and Repaglinide Alone and Combination

Abstract

Repaglinide and Metformin are used to treat Type 2 diabetes. Repaglinide with poor water solubility has relatively low oral bioavailability (56%) and undergoes hepatic first-pass metabolism. The oral bioavailability of metformin HCl is also low (about 50-60%). The purpose of this study was to prepare nanoemulsion formulations containing metformin HCl or repaglinide alone or in combination and characterize them in vitro and in vivo. Nanoemulsion formulations containing metformin HCl and/or repaglinide were successfully prepared and in vitro characterized. In addition, in vivo efficacy of nanoemulsion formulations was evaluated in a streptozotocin-nicotinamide-induced diabetic rat model. Biochemical, histopathological, and immunohistochemical evaluations were also performed. The mean droplet size and zeta potential values of nanoemulsion formulations were in the range of 110.15±2.64-120.23±2.16 nm and -21.95 - -24.33 mV, respectively. The percent entrapment efficiency values of nanoemulsion formulations were in the range of 93.600%-96.152%. All nanoemulsion formulations had a PDI of ≤0.223. A statistically significant decrease was observed in the blood glucose values of the diabetic rats treated with nanoemulsion formulations containing active substance/substances, compared to diabetic rats (control) (p<0.05). Nanoemulsion formulations (especially nanoemulsion containing metformin HCl and repaglinide combination) have a better antidiabetic activity and are more effective in reducing oxidative stress caused by diabetes.

Keywords: Diabetes mellitus; In vivo study; Metformin HCl; Nanoemulsion; Oxidative stress; Repaglinide.