Study of oral absorption of repaglinide loaded lipid based Nano formulation in rat

Abstract

Introduction: Repaglinide, due to its low solubility and high permeability, is classified as a drug with incomplete oral bioavailability. Lipid-based nanoformulations, including liposomes, nanoemulsions, etc., are effective in optimizing drug delivery due to their amphiphilic nature and can enhance the drug's bioavailability.Purpose: we aimed to investigate the oral absorption of repaglinide in three lipid nanoparticle formulations and its free form after oral administration to rats.Methods: After the preparation and characterization of optimized lipid nanoparticles loaded with repaglinide, intestinal absorption was assessed using the single-pass intestinal perfusion method. A segment of approximately 10 cm of the jejunum from an anesthetized rat was cannulated, and the dispersion of the lipid nanoformulation or the solution of the pure drug was passed through this segment in phosphate-buffered saline. The effluent samples were collected at 10-minute intervals, and the remaining drug content in the samples was quantified by HPLC. Results: In the evaluation of the physical properties of the nanoparticles, the size of particles loaded with the drug for the SLN, SNEDDS, and liposomal forms were 161.6 nm, 191.6 nm, and 176.4 nm, respectively. Additionally, the percentage of cumulative release in the free solution and SLN formulation was 59.78% and 107.19%, respectively, which was significantly higher in the solid lipid nanoparticles. Finally, the effective intestinal permeability was found to be 0.001826 ± 0.000188 cm/s for the free drug form, 0.00386 ± 0.000979 cm/s for the SNEDDS formulation, 0.007179 ± 0.002727 cm/s for the SLN formulation, and 0.007316 ± 0.002981 cm/s for the liposomal form of the drug. Conclusion: The intestinal permeability of repaglinide increases with the use of lipid nanoparticles. In this study, the liposomal and solid lipid nanoparticle (SLN) formulations, unlike the self-nanoemulsifying drug delivery system (SNEDDS), exhibited greater intestinal permeability compared to the free solution.