目的 研究并比较同一厂家不同产地的双氯芬酸钠肠溶片体外溶出行为的差异。方法 采用《中国药典》通则溶出度第一法与第二法装置绘制肠溶片在多种介质中的溶出曲线;考察酸性介质溶出阶段与缓冲液介质的离子强度对制剂溶出行为的影响。结果 双氯芬酸钠肠溶片在pH 1.0、5.5、6.0与6.8介质中的溶出曲线可作为该制剂的特征溶出曲线;3个来源的肠溶片经酸性介质溶出2 h后,体外溶出行为相似;不经酸性介质阶段,溶出行为差异较大;缓冲液介质的离子强度越大,肠溶包衣的溶解速率越快,肠溶片的溶出速率越快。结论 双氯芬酸钠肠溶片的溶出行为决定于肠溶包衣的溶解速率与片芯的溶出速率,在制剂开始溶出后存在RSD较大的特点;酸性介质溶出阶段与缓冲液介质的离子强度对制剂的溶出行为存在影响;同一厂家不同产地的双氯芬酸钠肠溶片的体外溶出行为存在差异。本实验旨在为仿制药一致性评价中多来源参比制剂的遴选提供数据支持,为处方筛选与生物等效性风险评价提供参考。
Abstract
OBJECTIVE To investigate and compare the dissolution behaviors of diclofenac sodium enteric-coated tablets from Beijing Novartis, Turkey Novartis and German Novartis respectively. METHODS According to the dissolution test methods in Chinese Pharmacopoeia, the dissolution curves of the preparations in various media were investigated. Whether the dissolution stage in acidic medium has influence on the dissolution behavior as well as the influence of the ionic strength of buffer medium were investigated. RESULTS The dissolution curves of diclofenac sodium enteric-coated tablets in media of pH 1.0, 5.5, 6.0 and 6.8 could be used as the characteristic dissolution curves of the preparation. The dissolution behaviors of the three preparations after being dissolved in acidic medium for 2 h were similar; the dissolution behaviors were quite different without the dissoulution stage in acid medium; the larger the ionic strength of the buffer medium was, the faster the dissolution rate of the enteric coated tablets was. CONCLUSION The dissolution behavior of diclofenac sodium enteric-coated tablets depends on the dissolution rates of the enteric coating and the tablet core. The RSD of the dissolution rate just after the formulation starts to dissolute is large; the dissolution phase in acidic medium and the ionic strength of the buffer medium has influence on the dissolution behavior. There is difference in the in vitro dissolution behaviors of diclofenac sodium enteric-coated tablets from manufacturers in different areas of the same group. This study may provide data support for the selection of multi-source reference preparations in the evaluation of generic drug conformance, and plays an important role in guiding the prescription screening and bioequivalence risk assessment.
关键词
双氯芬酸钠肠溶片 /
离子强度 /
溶出曲线
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Key words
diclofenac sodium enteric-coated tablet /
ionic strength /
dissolution curve
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中图分类号：
R917
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参考文献
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脚注
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基金
北京市科委重点实验室创新基地培育与发展工程专项项目资助(课题编号Z161100005016013)
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