Advancing Repaglinide delivery: Development and evaluation of optimized liposomal systems

Repaglinide is a common oral medication used to manage type 2 diabetes. Its therapeutic potential is limited by its low oral bioavailability (approximately 50 %) and short plasma half-life (around 1 h), necessitating frequent dosing. This study aimed to enhance Repaglinide's bioavailability and prolong its therapeutic effect by designing a novel sustained-release liposomal delivery system. The liposomes were fabricated using the hand-shake method, incorporating phospholipid, chitosan, and glycerol phosphate as key formulation components. The developed systems were evaluated for vesicle size, zeta potential, surface morphology, drug entrapment efficiency, in-vitro release profile, in-vivo performance, and storage stability. Fourier-transform infrared spectroscopy and differential scanning calorimetry analyses confirmed no chemical interactions between the drug and excipients. Entrapment efficiency was high, ranging from 77.1 % to 99.55 %. The liposomal vesicles were spherical and micron-sized (2.01–5.34 µm), with an optimal formulation (F9) exhibiting a low polydispersity index (0.053) and a high positive zeta potential (+49.03 mV), indicating good stability. The in-vitro drug release study demonstrated sustained diffusion, with the best-performing formulation (F9) achieving 85.21 ± 0.002 % cumulative release over 12 h. Release kinetic analysis indicated that the drug release best followed the Higuchi model (R² = 0.9812), suggesting a diffusion-controlled mechanism. An in-vivo study in a diabetic rat model confirmed the formulation's prolonged blood glucose-lowering effect, maintaining significantly lower glucose levels from the 6th to the 12th hour compared to a marketed product. Stability studies indicated that the optimized formulation maintained its key physicochemical properties when stored at 2–8 °C. In conclusion, the optimized liposomal system successfully enhanced the entrapment and provided sustained release of Repaglinide, significantly improving its in vivo efficacy and stability, thereby offering a promising strategy to overcome its pharmacokinetic limitations. • Optimized liposomes enhance Repaglinide bioavailability and release. • F9 formulation shows 99.25 % entrapment, + 49.03 mV zeta potential. • In vitro release sustained up to 12 h with 85.21 % drug diffusion. • In vivo study confirms better glycemic control vs marketed drug.