Northeastern University, Snell Engineering Center, Boston, Massachusetts 02115, USA.
Biotechnol Bioeng. 2010 Feb 1;105(2):421-30. doi: 10.1002/bit.22524.
A model was developed for predicting the influence of cyclodextrins (CDs) delivered as a physical mixture with drug on oral absorption. CDs are cyclic oligosaccharides which form inclusion complexes with many drugs and are often used as solubilizing agents. The purpose of this work is to compare the simulation predictions with in vitro as well as in vivo experimental results to test the model's ability to capture the influence of CD on key processes in the gastrointestinal (GI) tract environment. Dissolution and absorption kinetics of low solubility drugs (Naproxen and Nifedipine) were tested in the presence and absence of CD in a simulated gastrointestinal environment. Model predictions were also compared with in vivo experimental results (Glibenclamide and Carbamazepine) from the literature to demonstrate the model's ability to predict oral bioavailability. Comparisons of simulation and experimental results indicate that a model incorporating the influence of CD (delivered as a physical mixture) on dissolution kinetics and binding of neutral drug can predict trends in the influence of CD on bioavailability. Overall, a minimal effect of CD dosed as a physical mixture was observed and predicted. Modeling may aid in enabling rational design of CD containing formulations.
建立了一个模型来预测作为药物物理混合物给药的环糊精 (CD) 对口服吸收的影响。CD 是环状低聚糖，可与许多药物形成包合络合物，常用于增溶。这项工作的目的是将模拟预测与体外和体内实验结果进行比较，以测试模型捕捉 CD 对胃肠道 (GI) 环境中关键过程影响的能力。在模拟胃肠道环境中，测试了低溶解度药物（萘普生和硝苯地平）在存在和不存在 CD 的情况下的溶解和吸收动力学。还将模型预测与文献中的体内实验结果（格列本脲和卡马西平）进行了比较，以证明模型预测口服生物利用度的能力。模拟和实验结果的比较表明，纳入 CD（作为物理混合物给药）对溶解动力学和中性药物结合影响的模型可以预测 CD 对生物利用度影响的趋势。总体而言，观察到并预测了 CD 作为物理混合物给药的最小影响。建模可能有助于实现含 CD 配方的合理设计。
