A novel in vitro and numerical analysis of shear-induced drug release from extended-release tablets in the fed stomach
A novel in vitro and numerical analysis of shear-induced drug release from extended-release tablets in the fed stomach
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DOI：
10.1007/s11095-005-5272-x
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发表时间：
2005-08-01
影响因子：
3.7
通讯作者：
Brasseur, JG
中科院分区：
文献类型：
--
作者：
Abrahamsson, B;Pal, A;Brasseur, JG
目的.设计一种体外装置，可以模拟在体内范围内的表面剪切应力相关的人胃进食条件下。将计算机模拟与体外实验相结合，以量化片剂侵蚀速率与表面剪切应力。从两个独立的计算机模型，片剂在喂胃和片剂在体外，我们首先估计胃内的范围内的表面应力和雷诺数（Re），然后设计了一个溶出装置和参数空间，以复制在体内的条件。体外片剂侵蚀通过新的旋转烧杯装置测定，该装置提供片剂上可预测的表面剪切。通过改变测试介质的粘度和烧杯的旋转速率获得在体内相关的表面剪切应力的范围内，测量两种不同的延长释放片剂的片剂质量侵蚀速率。质量侵蚀速率和表面剪切被发现是高度相关的。在“低”应力（< 35达因/cm（2））下，侵蚀速率随表面剪切力的增加而迅速增加，与片剂材料无关。在较高的表面应力，侵蚀是强烈的材料依赖性。剪切力对与进食状态相关的骨架片药物释放的影响首次可以通过体外溶出试验进行预测。
Purpose. To design an in vitro apparatus that could simulate the in vivo range of surface shear stresses relevant for the human stomach under fed conditions.Methods. Computer simulations were combined with in vitro experiments to quantify tablet erosion rate vs. surface shear stress. From two separate computer models, of tablets in the fed stomach and of tablets in vitro, we first estimated the intragastric range of surface stress and Reynolds number (Re), and then designed a dissolution apparatus and parameter space to replicate the in vivo conditions. The in vitro tablet erosion was determined by a new rotating beaker apparatus that provided predictable surface shear on tablets. Tablet mass erosion rates were measured for two different extended-release tablets at a range of in vivo relevant surface shear stresses obtained by varying viscosity of test media and rotation rate of the beaker.Results. Mass erosion rate and surface shear were found to be highly correlated. Erosion rate increased with surface shear more rapidly at "low" stresses (< 35 dyne/cm(2)) independent of tablet material. At higher surface stress, erosion was strongly material dependent.Conclusions. Shear force effects on drug release from matrix tablets relevant for fed state are for the first time possible to predict by in vitro dissolution testing.