新药研发中药物盐型的筛选策略.PDF

• 414 • 现代药物与临床 Drugs Clinic 第 27 卷 第 4 期 2012 年 7 月 新药研发中药物盐型的筛选策略 1,2 2* 3 2 秦 雪 ，王成港 ，兰 静 ，任晓文 1. 天津中医药大学，天津 300193 2. 天津药物研究院 释药技术与药代动力学国家重点实验室，天津 300193 3. 天津市药品审评中心，天津 300191 摘 要：在新药研发早期阶段，将候选化合物成盐是一种重要手段，可改善候选化合物的理化性质，如溶解度、结晶度、吸 湿性、熔点和固态稳定性等。药物盐型的筛选首先从反离子的选择开始，然后筛选结晶条件制备其相应的盐型，最后根据结 晶度、熔点、吸湿性、物理化学稳定性和晶型等因素确定药物的最终盐型。药物盐型的筛选对选择具有适宜药学性质的固态 剂型有重要的指导作用。 关键词：新药；候选化合物；盐型；溶解度；生物利用度；晶型 中图分类号：R97 文献标志码：A 文章编号：1674 - 5515(2012)04 - 0414 - 04 Salt type selection strategy in research and development of new drugs 1, 2 2 3 2 QIN Xue , WANG Cheng-gang , LAN Jing , REN Xiao-wen 1. Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China 2. State Key Laboratory of Drug Delivery Technology and Pharmacokinetics, Tianjin Institute of Pharmaceutical Research, Tianjin 300193, China 3. Tianjin Center for Drugs Evaluation, Tianjin 300191, China Abstract: During the early stage of new drug research and development, to make the candidate compounds be salt is an important method for developing new drug, which could modify the physicochemical properties, such as solubility, crystallinity, hygroscopicity, melting point, and solid state stability. Salt type screening starts with the selection of possible counter ions, followed by the screening of crystallization conditions and the preparation of different salts. The final salt is determined by the crystallinity, melting point, hygroscopicity, physicochemical stability, crystal type, and some other factors. The salt type selection of new drugs could provide the guides for the selection of proper solid dosage forms with appropriate pharmaceutical properties. Key words: new drugs; candidate compounds; salt type; solubility; bioavailability; crystal type 高通量筛选技术和组合化学在药学领域的应用