Ubaid Muhammad, Shah Syed Nisar Hussain, Khan Shujaat Ali, Murtaza Ghulam
Department of Pharmacy, COMSATS Institute of Information Technology, Abbottabad, Pakistan.
Department of Pharmacy, Bahauddin Zakariya University, Multan, Pakistan.
Curr Drug Deliv. 2018;15(9):1343-1358. doi: 10.2174/1567201815666180604111101.
In this study, central composite design was utilized for the optimization of genipin cross-linked chitosan/Eudragit®-L 100 interpenetrating hydrogel network films fabricated through solvent evaporation technique.
Hydrogel formulations were studied using response surface methodology; regression analysis and the surface plots were used to evaluate the effect of variables on T50% (the time for 50% of drug release) and dynamic swelling with optimum formulation selection. Initial burst release of drug was observed from the formulated hydrogels during the first 2 hours of dissolution at simulated gastric pH 1.2 and then slow release during the next 10 hours in the simulated intestinal fluid at pH 7.4. Different polymer ratios in formulation showed significant influence on T50% and dynamic swelling of hydrogel. The highest T50% was observed at 9.89 hour and dynamic swelling at 7.86 h.
It was observed that by changing the polymer ratio with cross-linker, release rate of metformin could be modified. Cross-linker also affects drug release rate, i.e. the release rate is decreased with the increase in its concentration. The physical state of hydrogel was investigated by scanning electron microscope.
It indicated the uniform distribution of drug in hydrogel matrix system. Moreover, the presence of hydrogen and ionic bonds between polymers and crosslinking agent formed interpenetrating hydrogel network, likely responsible for increased value of T50%, as confirmed by FTIR. Acute oral toxicity study was performed to investigate the toxic effect of crosslinking agent and polymer used in formulations.
在本研究中，采用中心复合设计对通过溶剂蒸发技术制备的京尼平交联壳聚糖/聚丙烯酸树脂L100互穿水凝胶网络薄膜进行优化。
使用响应面法研究水凝胶配方；采用回归分析和表面图来评估变量对T50%（药物释放50%的时间）和动态溶胀的影响，并选择最佳配方。在模拟胃液pH 1.2条件下溶解的前2小时内，观察到所制备水凝胶的药物初始突释，然后在pH 7.4的模拟肠液中接下来的10小时内缓慢释放。配方中不同的聚合物比例对水凝胶的T50%和动态溶胀有显著影响。观察到最高T50%为9.89小时，动态溶胀为7.86小时。
观察到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。交联剂也影响药物释放速率，即随着其浓度的增加释放速率降低。通过扫描电子显微镜研究水凝胶的物理状态。
表明药物在水凝胶基质系统中分布均匀。此外，聚合物与交联剂之间存在氢键和离子键，形成了互穿水凝胶网络，这可能是T50%值增加的原因，傅里叶变换红外光谱证实了这一点。进行急性口服毒性研究以调查配方中使用的交联剂和聚合物的毒性作用。
