胃蛋白酶片质量分析及探索性研究

目的：评价国内不同企业生产的胃蛋白酶片的质量，并从溶出线、纯度、比活力等方面进行探索性研究，为企业提高产品质量提供改进方法。方法：采用4种溶出介质考察各企业产品的溶出行为；采用HPLC法，以1.7mol?L-1硫酸铵磷酸盐缓冲液（pH7.0）为流动相，梯度洗脱的方法测定胃蛋白酶片的纯度，并与SDS-PAGE蛋白电泳进行比对；采用蛋白质测定法与效价测定法对比活力进行研究。结果：（1）53批样品中，溶出度最大值为112%，最小值为28%；（2）HPLC结果与SDS-PAGE电泳结果显示胃蛋白酶为多组份物质；（3）原料比活力为12.2~13.2单位?mg -1蛋白，片剂比活力为8.0~15.3 单位?mg -1蛋白。结论：胃蛋白酶片现行质量标准安全性和有效性指标控制不足，建议企业加强药品生产全过程风险管理，降低产品批次间的批间差异，进一步提高制剂工艺的稳定性。本文为全面评价胃蛋白酶片的质量和完善其质量标准提供借鉴和参考。

Quality Analysis and Exploratory Research of Pepsin Tablets

ABSTRACT OBJECTIVE: To evaluate the quality of pepsin tablets produced by different enterprises in China, and investigate the dissolution, purity, specific activity to provide the direction for improving the quality of products for enterprises. METHODS: The release curves of pepsin tablets from different manufacturers were tested in both 4 dissolution mediums. A gradient HPLC method using phosphate buffered solution containing 1.7mol?L-1 ammonium sulfate as mobile phase was developed to determine the purity, and the results was compared with sodium dodecyl sulfate polyacrylamide gel electrophoresis. Classical Kieldahl method and potency test were used to determine the specific activity. RESULTS: The average dissolution was 59%, ranging from 28% to 112% in total of 53 batches of samples; The result of HPLC was in accordance with that of SDS-PAGE, indicated that pepsin was a complex protein; The specific activity of raw material was 12.2~13.2 u?mg -1 protein, and that of tablets was 8.0~15.3 u?mg -1 protein. CONCLUSIONS: The current standard of pepsin tablets should be further improved in safety and efficiency. It is recommended that manufacturers should strengthen the risk control of the whole process of production and effectively control all the influencing factors, to decrease inter batch variation and improve the stability of process. We provide useful reference for complete evaluation and the improvement of the quality standard of pepsin tablets.