| 张青青,张广超,康丽洁,石蓓佳,陆益红.基于渗透速率及溶出曲线初步预测国产氯唑沙宗片的生物等效性[J].中国药事,2023,(6):687-695 |
| 基于渗透速率及溶出曲线初步预测国产氯唑沙宗片的生物等效性 |
| Preliminary Prediction of Bioequivalence of Domestic Chlorzoxazone Tablets Based on Permeation Rate and In Vitro Dissolution Curve |
| 投稿时间：2022-06-23 |
| DOI：10.16153/j.1002-7777.2023.06.008 |
| 中文关键词: 氯唑沙宗片 BCS生物药剂学分类系统分类 体外溶出曲线 渗透速率 生物等效性 |
| 英文关键词: chlorzoxazone tablets BCS classifi cation dissolution curve permeation rate bioequivalence |
| 基金项目:重大新药创制科技重大专项《药物一致性评价关键技术与标准研究》(编号 2017zx09101001) |
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| 中文摘要: |
| 目的：从氯唑沙宗原料药的生物药剂学分类系统(BCS)分类出发，结合氯唑沙宗片的渗透速率及溶出曲线，对国产氯唑沙宗片仿制药与参比制剂的生物等效性进行初步预测。方法：采用人工仿生膜测定氯唑沙宗原料药渗透性，结合其在不同介质中的溶解度，对氯唑沙宗进行BCS分类判断。 选择水、pH 1.2盐酸溶液、pH 4.0磷酸盐缓冲液、pH 6.8磷酸盐缓冲液作为溶出介质，分别采用相似因子(f 2 )法、AV值法及非模型依赖多变量置信区间法，对参比制剂与4家企业的国产氯唑沙宗片在不同介质中的溶出曲线进行相似性评价。计算仿制制剂与参比制剂在空腹肠及饱腹肠模拟液溶出介质中的渗透速率及总渗透量的90%置信区间，进行生物等效性预测。结果：氯唑沙宗为BCS Ⅱ类，低溶解度高渗透性药物。体外溶出试验显示国产氯唑沙宗片与参比制剂的相似性较低。渗透速率试验显示，在空腹肠模拟液溶出介质中，与参比制剂渗透速率的90%置信区间分别为101.05%~107.12%、 116.57%~120.13%、99.36%~105.72%、130.17%~139.62%之间，其中3家在80%~125%的生物等效接受标准范围内，1家不在范围内。在饱腹肠模拟液溶出介质中，与参比制剂渗透速率的90%置信区间分别为103.62%~115.49%、116.99%~134.85%、131.70%~141.93%、122.37%~127.23%，其中1家在 80%~125%的生物等效接受标准范围内，3家不在范围内。结论：基于溶出曲线结合渗透速率可在一定程度上较好地模拟药物在人体内的吸收转运过程，该联合应用方法可用于国产氯唑沙宗片与参比制剂生物等效性的初步预测。 |
| 英文摘要: |
| Objective: To preliminarily predict the bioequivalence of domestic generic drugs of chlorzoxazone tablets and reference listed drugs (RLD) based on the BCS (biopharmaceutical classifi cation system) classifi cation of chlorzoxazone APIs, combined with the permeationrate and the dissolution curve of chlorzoxazone tablets. Methods: Determine BCS classifi cation of chlorzoxazone by measuring the permeability of chlorzoxazone APIs with artifi cial biomimetic membrane and its solubility in diff erent media. Similarity factor (f 2 ), AV value and model-independent multivariate confi dence interval method were used to evaluate the similarity of dissolution curves between RLD and four domestic chlorzoxazone tablets in different media including water, pH 1.2 hydrochloric acid solution, pH 4.0 phosphate buff er and pH 6.8 phosphate buff er. The 90% confi dence interval of permeationrate and total permeation volume in fasting and fed intestine simulated solution dissolution medium were calculated to assess the bioequivalence of domestic generic drugs and the RLD. Results: Chlorzoxazone was classifi ed as BCS Ⅱ drug with low solubility and high permeability. The in vitro dissolution tests showed that the similarity between domestic chlorzoxazone tablets and the RLD was low. The permeation rate tests showed that in fasting intestinal simulated solution dissolution medium, the 90% confi dence intervals of the permeation rates of domestic chlorzoxazone tablets and the RLD from four manufacturers were 101.05%~107.12%, 116.57%~120.13%, 99.36%~105.72% and 130.17%~139.62%. Three of them were within the range of 80%~125% of the acceptance criteria for bioequivalence while the other one was not. Respectively, while in fed simulated solution dissolution medium, the 90% confidence interval of the permeation rates of domestic chlorzoxazone tablets and the RLD from four manufacturer were 103.62%~115.49%, 116.99%~134.85%, 131.70%~141.93% and 122.37%~127.23%. One of them was within the range of 80%~125% of the acceptance criteria for bioequivalence while the other three were not. Conclusion: Based on the combination of dissolution curve and permeationrate could be better simulated the absorption and transport process in vivo to some extent, the combined application method could be used for the preliminary prediction of the bioequivalence between domestic chlorzoxazone tablets and reference preparations. |
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