中国药物警戒 ›› 2026, Vol. 23 ›› Issue (6): 636-642.
DOI: 10.19803/j.1672-8629.20260172

• 基础与临床研究 • 上一篇    下一篇

高效液相色谱法测定乙醇对阿司匹林肠溶片体外释放行为的影响

庄杰1,2, 綦梦洁1, 杨世婕1,2, 翟晨斐1, 牛剑钊1, 许风国2, 刘倩1,*   

  1. 1中国食品药品检定研究院化学药品检定所,北京 100050;
    2中国药科大学药学院,江苏 南京 210009
  • 收稿日期:2026-03-05 出版日期:2026-06-15 发布日期:2026-06-18
  • 通讯作者: *刘倩,女,博士,研究员,药品检验研究。E-mail: liuqian@nifdc.org.cn
  • 作者简介:庄杰,男,在读硕士,药品检验研究。
  • 基金资助:
    国家重点研发计划（2020YFE0201700）; 国家药品监督管理局重点实验室学科建设课题（2024HYZX04）

Effects of Ethanol on the in vitro Release Behavior of Aspirin Enteric-Coated Tablets by HPLC

ZHUANG Jie1,2, QI Mengjie1, YANG Shijie1,2, ZHAI Chenfei1, NIU Jianzhao1, XU Fengguo2, LIU Qian1,*   

  1. 1Institute for Chemical Drug Control, National Institutes for Food and Drug Control, Beijing 100050, China;
    2School of Pharmacy, China Pharmaceutical University, Nanjing Jiangsu 210009, China
  • Received:2026-03-05 Online:2026-06-15 Published:2026-06-18

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摘要： 目的 依据国家药品监督管理局发布的指导原则对不同生产企业阿司匹林肠溶片仿制制剂及参比制剂的乙醇剂量倾泻风险进行对比研究。方法 采用含0%~40%乙醇的0.1 mol·L-1盐酸溶液模拟胃内环境,通过高效液相色谱法测定阿司匹林肠溶片在不同乙醇浓度中的体外释放程度,绘制溶出曲线,通过计算相似因子（f2）评价不同制剂体外释放的相似性。结果 在含5%、20%乙醇的溶出介质中,各生产企业制剂均表现出较好的耐酸性,120 min内溶出量≤10%,仿制制剂与参比制剂的体外释放量无明显差异;乙醇浓度升至40%时,所有制剂的肠溶包衣完整性均遭破坏,超过90%的显著剂量倾泻并伴随药物降解。结论 含40%乙醇的盐酸介质会诱导阿司匹林肠溶片发生剂量倾泻。推测肠溶包衣的材料是引起乙醇剂量倾泻的关键因素,提示阿司匹林肠溶片与含酒精饮料同服存在安全风险。

关键词: 阿司匹林肠溶片, 乙醇剂量倾泻, 高效液相色谱法, 安全性评价, 体外释放实验

Abstract: Objective To compare the ethanol dose-dumping risk between generic and reference formulations of aspirin enteric-coated tablets from different manufacturers in accordance with the guidelines issued by the National Medical Products Administration (NMPA). Methods The gastric environment was simulated using 0.1 moL·L-1 hydrochloric acid containing 0% to 40% ethanol. The in vitro release of aspirin was determined by high-performance liquid chromatography (HPLC). Dissolution profiles were generated, and the similarity of in vitro release between formulations was evaluated by calculating the similarity factor (f2). Results In media containing 5% and 20% ethanol, the acid resistance of all the tested formulations proved satisfactory, with a cumulative release of ≤10% within 120 min. The in vitro release from the generic and reference formulations hardly changed. When the ethanol concentration was raised to 40%, the integrity of the enteric coating of all the formulations was disrupted, resulting in dose dumping (>90%) accompanied by drug degradation. Conclusion Ethanol at the concentration of 40% can induce dose dumping of aspirin enteric-coated tablets. The enteric coating material is believed to be the leading contributor to ethanol-induced dose dumping, which suggests a safety risk once these tablets are co-administered with alcoholic beverages.

Key words: Aspirin Enteric-Coated Tablets, Alcohol-Induced Dose Dumping, High Performance Liquid Chromatography (HPLC) Method, Safety Evaluation, In vitro Release Test

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