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首页> 美国卫生研究院文献>AAPS PharmSci >Prediction of dissolution-absorption relationships from a continuous dissolution/Caco-2 system
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Prediction of dissolution-absorption relationships from a continuous dissolution/Caco-2 system

机译：通过连续溶出/ Caco-2系统预测溶出-吸收关系

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The objectives were 1) to design a continuous dissolution Caco-2 system to predict the dissolution-absorption relationships for fast and slow dissolving formulations of piroxicam, metoprolol tartrate, and ranitidine HCl, and compare the predicted relationships with observed relationships from clinical studies; 2) to estimate the effect of croscarmellose sodium on ranitidine dissolution-absorption relationships; and 3) to estimate the effect of solubilizing agents on piroxicam dissolution-absorption relationships. A continuous dissolution/Caco-2 system was constructed from a dissolution apparatus and a diffusion cell, such that drug dissolution and permeation across a Caco-2 monolayer would occur sequentially and simultaneously. The continuous system generally matched observed dissolution-absorption relationships from clinical studies. For example, the system successfully predicted the slow metoprolol and slow ranitidiine formulations to be permeation-rate-limited. The system predicted the slow piroxicam formulation to be dissolution-rate-limited, and the fast piroxicam formulation to be permeation-rate-limited, in spite of piroxicam’s high permeability and low solubility. Additionally, the system indicated croscarmellose sodium enhanced ranitidine permeability and predicted solubilizing agents to not modulate permeability. These results suggest a dissolution/Caco-2 system to be an experimentally based tool that may predict dissolution-absorption relationships from oral solid dosage forms, and hence the relative contributions of dissolution and permeation to oral drug absorption kinetics.
机译：目的是：1）设计一个连续溶出Caco-2系统，以预测吡罗昔康，酒石酸美托洛尔和盐酸雷尼替丁的快速和缓慢溶出制剂的溶出-吸收关系，并将预测的关系与临床研究中观察到的关系进行比较； 2）评估交联羧甲基纤维素钠对雷尼替丁溶解-吸收关系的影响；和3）估计增溶剂对吡罗昔康溶解-吸收关系的影响。由溶出度仪和扩散池构建连续溶出度/ Caco-2系统，使药物在Caco-2单层中的溶出和渗透将依次发生并同时发生。连续系统通常匹配临床研究中观察到的溶出-吸收关系。例如，该系统成功地预测了慢速美托洛尔和慢速拉尼二胺制剂受到渗透速率的限制。该系统预测，尽管吡罗昔康具有高渗透性和低溶解度，但慢速吡罗昔康配方的溶解速率受到限制，而快速吡罗昔康配方的渗透速率受到限制。另外，该系统表明交联羧甲基纤维素钠提高了雷尼替丁的渗透性，并预测增溶剂不会调节渗透性。这些结果表明，溶出/ Caco-2系统是一种基于实验的工具，可以预测口服固体剂型的溶出-吸收关系，从而预测溶出和渗透对口服药物吸收动力学的相对贡献。

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