Profiling biopharmaceutical deciding properties of absorption of lansoprazole enteric-coated tablets using gastrointestinal simulation technology
Profiling biopharmaceutical deciding properties of absorption of lansoprazole enteric-coated tablets using gastrointestinal simulation technology
复制标题
利用胃肠道模拟技术分析决定兰索拉唑肠溶片吸收的生物制药特性
DOI：
10.1016/j.ijpharm.2013.06.034
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发表时间：
2013-09-10
影响因子：
5.8
通讯作者：
He, Zhonggui
中科院分区：
文献类型：
--
作者：
Wu, Chunnuan;Sun, Le;He, Zhonggui
本研究的目的是将药物制剂的体外性质与其体内性能相关联，并阐明口服吸收的决定性性质。采用胃肠模拟技术（GST）模拟体内血药浓度-时间曲线，并由GastroPlus（TM）软件实现。兰索拉唑是一种典型的BCS II类药物，被选为模型药物。首先，测定兰索拉唑的理化和药动学参数或从文献中收集这些参数以构建模型。通过比较预测的和实验的血浆浓度数据，进行开发的模型的验证。我们发现预测曲线与实验数据吻合得很好。然后进行参数敏感性分析（PSA），以找到口服吸收的关键参数。兰索拉唑肠溶片的吸收对剂量、溶解度和粒度特别敏感。单次剂量为30 mg，溶解度为0.04 mg/ml，吸收完全。当兰索拉唑颗粒半径降至约25 μ m时，可实现良好的吸收。综上所述，GST是一个有用的工具，用于描述生物制药决定兰索拉唑肠溶片的吸收特性和指导处方优化。皇冠版权所有（C）2013由爱思唯尔B. V.出版保留所有权利。
The aim of the present study was to correlate in vitro properties of drug formulation to its in vivo performance, and to elucidate the deciding properties of oral absorption. Gastrointestinal simulation technology (GST) was used to simulate the in vivo plasma concentration-time curve and was implemented by GastroPlus (TM) software. Lansoprazole, a typical BCS class II drug, was chosen as a model drug. Firstly, physicochemical and pharmacokinetic parameters of lansoprazole were determined or collected from literature to construct the model. Validation of the developed model was performed by comparison of the predicted and the experimental plasma concentration data. We found that the predicted curve was in a good agreement with the experimental data. Then, parameter sensitivity analysis (PSA) was performed to find the key parameters of oral absorption. The absorption was particularly sensitive to dose, solubility and particle size for lansoprazole enteric-coated tablets. With a single dose of 30 mg and the solubility of 0.04 mg/ml, the absorption was complete. A good absorption could be achieved with lansoprazole particle radius down to about 25 pm. In summary, GST is a useful tool for profiling biopharmaceutical deciding properties of absorption of lansoprazole enteric-coated tablets and guiding the formulation optimization. Crown Copyright (C) 2013 Published by Elsevier B.V. All rights reserved.