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

Repaglinide and Metformin are used to treat Type 2 diabetes. Repaglinide with poor water solubility has rela-tively 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 formula-tions 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 strep-tozotocin-nicotinamide-induced diabetic rat model. Biochemical, histopathological, and immunohistochemi-cal 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 sub-stance/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.(c) 2023 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.