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The solubility-permeability interplay and oral drug formulation design: Two heads are better than one

机译:溶解度-渗透性相互作用和口服药物制剂设计:两个头比一个头好

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摘要

Poor aqueous solubility is a major challenge in today's biopharmaceutics. While solubility-enabling formulations can significantly increase the apparent solubility of the drug, the concomitant effect on the drug's apparent permeability has been largely overlooked. The mathematical equation to describe the membrane permeability of a drug comprises the membrane/aqueous partition coefficient, which in turn is dependent on the drug's apparent solubility in the GI milieu, suggesting that the solubility and the permeability are closely related, exhibit a certain interplay between them, and treating the one irrespectively of the other may be insufficient. In this article, an overview of this solubility-permeability interplay is provided, and the available data is analyzed in the context of the effort to maximize the overall drug exposure.
机译:水溶性差是当今生物制药的主要挑战。尽管使溶解度提高的制剂可以显着增加药物的表观溶解度,但对药物的表观渗透性的伴随作用已被大大忽略。描述药物的膜渗透性的数学方程包括膜/水分配系数,而膜/水分配系数又取决于药物在GI环境中的表观溶解度,表明溶解度和渗透性密切相关,在药物之间存在一定的相互作用它们,并且一视同仁可能不够。在本文中,提供了这种溶解度-渗透性相互作用的概述,并在努力使总体药物暴露最大化的背景下分析了可用数据。

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