阿司匹林肠溶片的实时释放度相似性分析研究

目的: 考察不同厂家生产的阿司匹林肠溶片体外实时释放曲线,比较不同来源阿司匹林肠溶片释放行为的差异,为提高阿司匹林肠溶片的处方设计和质量控制提供思路及手段.方法: 采用光纤药物释放度实时测定仪,测定各厂家阿司匹林肠溶片在pH 6.8(中国药典2010年版)、pH 6.8(日本橙皮书)、pH 6.0(日本橙皮书)、pH 4.0缓冲液和pH 1.2盐酸溶液5种释放介质中的实时释放曲线.结果: 参比制剂在2种pH 6.8和pH 6.0缓冲液释放介质中,50 min内的释放量均可达到80%;以pH 6.8缓冲液(中国药典2010年版)为释放介质,31家企业的阿司匹林肠溶片在45 min内的释放量均大于80%,且均一性良好;以pH 6.0缓冲液(日本橙皮书)为释放介质,部分企业的阿司匹林肠溶片在50 min内的释放量均小于20%,且180 min内的释放量仍小于50%;以pH 6.8缓冲液(日本橙皮书)为释放介质,仅有部分厂家的阿司匹林肠溶片在2种pH 6.8缓冲液中表现出相似的释放行为,另一部分厂家的阿司匹林肠溶片释放较慢或不释放;pH 4.0缓冲液和pH 1.2盐酸溶液为溶出介质,参比制剂和受试制剂均未释放.结论: 参比制剂在pH 6.0以及不同离子种类及强度下的pH 6.8的缓冲液释放介质中均能释放,表明参比制剂在大部分肠道内均能够进行释放,并且受肠道内环境影响较小.部分企业阿司匹林肠溶片与参比制剂在释放度行为上存在差异,需重视处方工艺的进一步研究;建议采用多条释放曲线评价阿司匹林肠溶片的质量.

Objective: To study the real-time release curves of aspirin enteric-coated tablets from different manufacturers and compare the difference of their release behaviors so as to provide ideas and effective methods for further improvement of the prescription design and quality control of aspirin enteric coated tablets. Methods: With fiber-optic in situ dissolution tester, the release curves of enteric-coated tablets from different manufacturers were tested in pH 6.8(ChP 2010), pH 6.8(Japanese Orange Book), pH 6.0(Japanese Orange Book), pH 4.0 phosphate buffer solutions and pH 1.2 hydrochloric acid solution. Results: In pH 6.8 and pH 6.0 buffer dilutions, the reference preparation released 80% in 50 minutes.In the pH 6.8(ChP 2010)buffer dilution as the release medium, aspirin enteric-coated tablets from 31 different manufacturers released 80% in 45 minutes, and their uniformities were good.In the pH 6.0 buffer solution(Japanese Orange Book)as the release medium, aspirin enteric-coated tablets from some manufacturers released less than 20% in 50 minutes and still less than 50% in 180 minutes.In the pH 6.8 buffer solution(Japanese Orange Book)as the release medium, the test preparations from only a few manufacturers showed similar release behaviors in two kinds of pH 6.8 buffer solutions and those from other manufacturers released slowly or did not release.In pH 4.0 buffer solution and pH 1.2 hydrochloric acid solution, none of the test preparations and the reference preparation released. Conclusion: The reference preparation can release in pH 6.0 buffer solution and in two kinds of pH 6.8 buffer solutions with different ionic species and strength, which showed that the reference preparation can release in most intestines, and was influenced rarely by the environment of intestines.There remained differences in release behavior between aspirin enteric-coated tablets from different manufacturers and the reference preparation, which called for further study focusing on the prescription process.It is suggested that multiple release curves used to evaluate the quality of aspirin enteric-coated tablets.