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

Kaplan A. B., Cetin M., Bayram C., Yildirim S., Taghizadehghalehjoughi A., Hacimuftuoglu A.

JOURNAL OF PHARMACEUTICAL SCIENCES, vol.112, no.5, pp.1411-1426, 2023 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 112 Issue: 5
  • Publication Date: 2023
  • Doi Number: 10.1016/j.xphs.2023.01.008
  • Journal Name: JOURNAL OF PHARMACEUTICAL SCIENCES
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Analytical Abstracts, BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, Chemical Abstracts Core, Chimica, EMBASE, International Pharmaceutical Abstracts, MEDLINE, Veterinary Science Database
  • Page Numbers: pp.1411-1426
  • Keywords: Diabetes mellitus, In vivo study, Metformin HCl, Nanoemulsion, Oxidative stress, Repaglinide, DRUG-DELIVERY-SYSTEMS, OXIDATIVE STRESS, CYTOTOXICITY EVALUATION, INSULIN, APOPTOSIS, EXTRACT, HYDROCHLORIDE, INFLAMMATION, EFFICACY, TABLETS
  • Ataturk University Affiliated: Yes

Abstract

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.