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京尼平交联壳聚糖/明胶水凝胶的制备及性能表征及其在响应面法优化载盐酸二甲双胍口服给药系统中的应用。

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

机构信息

Department of Pharmacy, COMSATS Institute of Information Technology, Abbottabad, Pakistan.

Department of Pharmacy, COMSATS Institute of Information Technology, Abbottabad, Pakistan.

出版信息

Int J Biol Macromol. 2018 Jul 15;114:1174-1185. doi: 10.1016/j.ijbiomac.2018.04.023. Epub 2018 Apr 7.

DOI:10.1016/j.ijbiomac.2018.04.023
PMID:29634962
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 T and dynamic swelling of hydrogel. The highest T 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.

摘要

在这项研究中,采用中心复合设计,使用不同浓度的京尼平作为交联剂,制备并优化载有二甲双胍的壳聚糖-明胶水凝胶薄膜。采用溶剂蒸发技术制备水凝胶薄膜。将所制备的水凝胶在模拟胃液 pH1.2 中进行 3h 的药物释放研究。在胃模拟环境中溶解的前 2h 内,观察到水凝胶中存在初始突释。配方中不同聚合物比例对水凝胶的 T 和动态溶胀有显著影响。在 40.23min 时观察到最高的 T,在 9.1 时观察到动态溶胀。通过改变聚合物与交联剂的比例,可以改变二甲双胍的释放速率。交联剂的浓度增加也会影响释放速率,释放速率降低。通过扫描电子显微镜研究了水凝胶的物理状态。结果表明药物晶体均匀存在于水凝胶基质系统中。傅里叶变换红外光谱(FTIR)证实了聚合物和交联剂之间存在氢键和离子键,使药物在基质系统中保持完整。扫描电子显微镜(SEM)图像证实了药物的均匀分布。结论是,可以成功地使用 CHI 和 GLN 聚合物和不同浓度的交联剂制备出具有即时释放、pH 敏感性和良好安全性的水凝胶配方。

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