Fabrication and characterization of genipin cross-linked chitosan/gelatin hydrogel for pH-sensitive, oral delivery of metformin with an application of response surface methodology

Abstract

In this study, central composite design was utilized for the preparation and optimization of chitosan-gelatin hydrogel films containing metformin using different concentrations of genipin as crosslinking agent. Solvent evaporation technique was used to develop hydrogel films. The formulated hydrogels were subjected to study the drug release in the simulated gastric pH1.2 for 3h. Initial burst release was observed from hydrogel during the first 2h of dissolution in gastric simulated environment. Different polymer ratios in formulation showed significant influence on T50% and dynamic swelling of hydrogel. The highest T50% was observed at 40.23min and dynamic swelling at 9.1. It was observed that by changing the polymer ratio with cross-linker, release rate of metformin could be modified. Cross-linker also affects the release rate as its concentration increases, the release rate decreases. The physical state of hydrogel was investigated by scanning electron microscope. It indicated the uniform presence of drug crystals in hydrogel matrix system. Fourier transform infrared spectroscopy (FTIR) confirmed the presence of hydrogen and ionic bonds between polymers and crosslinking agent leaving the drug intact in the matrix system. Scanning electron microscopy (SEM) images confirmed the uniform drug distribution. As per conclusion, the immediate release, pH sensitive, hydrogel formulation with good safety profile can be successfully fabricated by using CHI and GLN polymers with varying concentration of crosslinking agent.