利格列汀双层缓释片的制备及体外释放研究

目的 制备一种新型利格列汀双层缓释片，并考察其体外释放行为。方法 以羟丙基甲基纤维素（hydroxyl propyl methyl cellulose，HPMC）为骨架材料、黄原胶为黏合剂，采用单因素设计筛选处方，进行利格列汀双层缓释片的制备，并绘制处方在pH 6.80介质中的体外溶出曲线；采用常规Ritger-Peppas、Higuchi、一级、零级释放曲线方程进行拟合，分析样品释药原理。结果 经优化后的样品由含药缓释层和含药速释层构成。缓释层由主成分利格列汀3 mg、缓释骨架材料HPMC（型号：K4M及K100M，用量均50 mg）、填充剂微晶纤维素100 mg、凝胶缓释基质黄原胶15 mg、润滑剂硬脂酸镁1 mg组成；速释层由主成分利格列汀2 mg、填充剂微晶纤维素10 mg、崩解剂交联聚乙烯吡咯烷酮15 mg、润滑剂硬脂酸镁1 mg组成。最终结果与零级释放方程匹配度最高，极具相关性，拟合结果r²无限接近于1。结论 成功制得利格列汀双层缓释片，并实现零级释放。

Study on Preparation Process and in Vitro Release Behavior of Linagliptin Double-layer Sustained-release Tablets

OBJECTIVE To prepare novel linagliptin sustained-release tablets with double layers and to investigate the in vitro release behavior. METHODS The formulation was evaluated with a single factor design, hydroxyl propyl methyl cellulose(HPMC) were used as skeletal material and xanthan gum were used as adhesive, the dissolution curve in vitro was draw in pH 6.80 medium. The Ritger-Peppas, Higuchi, zero-order and first-order release equations were used to fit the dissolution curves and the principle of drug release was analyzed. RESULTS The optimized sample was composed of a drug-containing sustained-release layer and a drug-containing immediate-release layer. The sustained-release layer was composed of ligliptin(the main component) 3 mg, HPMC(the sustained-release matrix material, the models were K4M and K100M) 50 mg, microcrystalline cellulose(the filler) 100 mg, xanthan gum(gel sustained-release matrix) 15 mg, magnesium stearate(lubricant) 1 mg. The immediate release layer was composed of ligliptin(the main component) 2 mg, microcrystalline cellulose(filler) 10 mg, polyplasdone(disintegrating agent) 15 mg, magnesium stearate(lubricant) 1 mg. The final result had the highest matching degree with the zero-order release equation and was highly correlated. The fitting result r² was infinitely close to 1. CONCLUSION The linagliptin sustained-release tablets with double layers are successfully prepared and zero-order release is realized.