目的 研究双氯芬酸钠经平行人工膜被动转运的渗透性,比较同一厂家不同地点生产的双氯芬酸钠肠溶片溶出度与膜渗透间的差异。方法 研究并测定了双氯芬酸钠在不同pH介质中的渗透性;通过比较3个产地肠溶片主成分膜渗透曲线的差异,考察了辅料对双氯芬酸钠渗透的影响;测定并比较了3个产地肠溶片,经酸性介质溶出2 h后,在pH 6.0与pH 6.8的介质中溶出曲线与膜渗透曲线的差异。结果 双氯芬酸钠在pH 5.0~6.8的介质中,渗透性随pH值的增大而减小,其中在pH 6.8介质中的渗透性最小,Pe为1.08×10-4 cm·s-1;3个产地肠溶片所用辅料不影响主成分的膜渗透。结论 双氯芬酸钠的渗透性与介质的pH值相关;双氯芬酸钠的生物药剂学分类为BCS Ⅱ类,即低溶解度,高渗透性药物;双氯芬酸钠肠溶片的溶出决定于肠溶包衣的溶解速率与片芯的溶出速率;同一集团不同产地的双氯芬酸钠肠溶片在pH 6.0与pH 6.8介质中的溶出行为存在差异,但膜渗透相似。本实验可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,对处方筛选与生物等效性风险评价具有指导作用。
Abstract
OBJECTIVE To investigate the permeability of diclofenac sodium(DS)through parallel artificial membrane, and compare the differences in the dissolution rates and fluxes of diclofenac sodium enteric-coated tablets from Novartis in Beijing, Turkey and Germany.METHODS The permeation of diclofenac sodium in different pH media was studied and determined.The effects of excipients on the permeability of diclofenac sodium were investigated by comparing the differences in the permeability of diclofenac sodium enteric-coated tablets.After being placed in acidic media of pH 6.0 and pH 6.8 for 2 h, the difference in the dissolution profiles and membrane fluxes of three sources diclofenac sodium enteric-coated tablets were determined and compared. RESULTS The permeability of diclofenac sodium in pH 5.0-6.8 medium increased with the decrease of pH value, which was the smallest in pH 6.8 medium (1.08×10-4 cm·s-1). The excipients did not affect the permeability of the main component. The dissolution rate of the sample from Turkey Novartis was slightly faster than those from Beijing and Germany Novartis. CONCLUSION The permeability of diclofenac sodium depends on the pH of the medium. The biopharmaceutics classification system(BCS) of diclofenac sodium is classified as class Ⅱ, a drug of low solubility and high permeability. The dissolution of diclofenac sodium enteric-coated tablets depends on the dissolving rate of the enteric-coating and the dissolution rate of the tablet core.The dissolution behaviors of diclofenac sodium enteric-coated tablets from different regions of the same company in pH 6.0 and pH 6.8 media are difference but the membrane fluxes are similar. 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 guiding role in prescription screening and bioequivalence risk assessment.
关键词
双氯芬酸钠 /
肠溶片 /
溶出 /
渗透 /
平行人工膜 /
生物药剂学分类
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Key words
diclofenac sodium /
enteric-coated tablet /
dissolution /
permeability /
parallel artificial membrane permeability assay /
biopharmaceutics classification system
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中图分类号：
R917
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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(Z161100005016013)
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