药学学报, 2019, 54(1): 1-7
引用本文:
章溢, 崔天, 李姝璇, 饶义琴, 胡海燕. 通过增加溶解度提高BCS Ⅱ类药物口服吸收:常常被忽略的药物渗透性[J]. 药学学报, 2019, 54(1): 1-7.
ZHANG Yi, CUI Tian, LI Shu-xuan, RAO Yi-qin, HU Hai-yan. Improving oral absorption of BCS Ⅱ drugs by increasing solubility: frequently overlooked permeability[J]. Acta Pharmaceutica Sinica, 2019, 54(1): 1-7.

通过增加溶解度提高BCS Ⅱ类药物口服吸收:常常被忽略的药物渗透性
章溢, 崔天, 李姝璇, 饶义琴, 胡海燕
中山大学药学院, 广东 广州 510006
摘要:
作为低溶解性/高渗透性的BCS Ⅱ类药物,提高溶解度被认为是提高其口服吸收的重要途径。近期的研究表明,采用某些制剂手段提高药物溶解度的同时会极大地降低其渗透性,继而影响药物的口服吸收。由于药物渗透性与膜/水分配系数相关,后者又受溶解度的影响,从而使药物溶解性和渗透性存在独特的关联性。采用制剂手段增加BCSⅡ类药物溶解度的同时倘若不考虑其对药物渗透性的影响,将难以实现药物最佳口服吸收的最大化。本文综述了常用制剂策略,如环糊精包合物、表面活性剂、混合潜溶剂和固体分散体等增加药物溶解度的同时对药物渗透性的影响,并评述了以上策略中新技术的运用及转运蛋白的影响,以期为以提高口服吸收为目的的制剂设计、辅料筛选和研究方法提供依据。
关键词:    BCS Ⅱ类药物      口服吸收      溶解度      渗透性      相关性     
Improving oral absorption of BCS Ⅱ drugs by increasing solubility: frequently overlooked permeability
ZHANG Yi, CUI Tian, LI Shu-xuan, RAO Yi-qin, HU Hai-yan
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China
Abstract:
BCS Ⅱ drugs are characterized by low solubility and high permeability. Improving their solubility is considered an important approach to improve its oral absorption. Recent strategies to increase the solubility of poorly-soluble drugs may unexpectedly result in greatly depressed permeability, ultimately leading to failure in improving oral absorption. Based on the mathematics of membrane permeability coefficient of a drug, the membrane/aqueous partition coefficient is dependent on the drug's solubility in the gastrointestinal milieu, suggesting a unique interplay between the solubility and permeability of the drug, and treating the one irrespectively of the other may be insufficient. When we focus on the increase of drug solubility and overlook the efficacy of drug permeability, the positive effect of increased solubility to drug oral absorption might be traded off by depressed permeability. To provide rational formulary designs, by optimizing excipients and evaluation, this review summarizes solubility-permeability interplay for different types of solubilizing techniques, such as cyclodextrin, surfactants-based vehicle, cosolvent, amorphous solid dispersions, other infectors such as P-gp transporters and new techniques for simultaneous evaluation of drug solubility and permeability.
Key words:    BCS Ⅱ drug    oral absorption    solubility    permeability    interplay   
收稿日期: 2018-10-16
DOI: 10.16438/j.0513-4870.2018-0933
基金项目: 国家自然科学基金资助项目(81473154,81773659);中山大学高校基本业务费青年教师重点培育项目(18ykzd08);中山大学实验室开放基金项目(20180270).
通讯作者: 胡海燕,Tel/Fax:86-20-39336119,E-mail:lsshhy@mail.sysu.edu.cn
Email: lsshhy@mail.sysu.edu.cn
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