Beijing Key Laboratory of Polymorphic Drugs, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.
Beijing Key Laboratory of Polymorphic Drugs, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.
J Pharm Sci. 2022 Oct;111(10):2839-2847. doi: 10.1016/j.xphs.2022.05.009. Epub 2022 May 14.
Piperazine (PIP) is a pharmaceutically acceptable molecule and a good co-conformer in crystallographic engineering. Most of the non-steroidal anti-inflammatory drugs (NSAIDs) have poor aqueous solubility, which hinders their clinical application. The reports show that the solubility of many insoluble drugs can be significantly improved through salt formation with the PIP. In this work, we obtained a series of NSAIDs-PIP salts, such as ibuprofen-piperazine (IBU-0.5PIP) salt, indomethacin-piperazine (IND-0.5PIP) salt, sulindac-piperazine (SUL-0.5PIP) salt, phenylbutazone-piperazine (PBZ-0.5PIP) salt, ketoprofen-piperazine (KPF-0.5PIP) salt and flurbiprofen-piperazine (FLB-0.5PIP) salt. The spatial structure, arrangement, interaction and associations were expatiated by single crystal X-ray diffraction. Powder X-ray diffraction, Fourier transform infrared, differential scanning calorimetry, and thermogravimetric analysis were used to characterize the novel salts. The six new salts had more than 10 folds of solubility and a faster dissolution rate improved corresponding to the bulk drugs in pure water, and the significant improvement of solubility is closely related to the structure of salts.
哌嗪（PIP）是一种药用可接受的分子，也是晶体工程中的一种良好共构体。大多数非甾体抗炎药（NSAIDs）的水溶性较差，这阻碍了它们的临床应用。报告表明，许多难溶性药物的溶解度可以通过与 PIP 形成盐来显著提高。在这项工作中，我们获得了一系列 NSAIDs-PIP 盐，如布洛芬-哌嗪（IBU-0.5PIP）盐、吲哚美辛-哌嗪（IND-0.5PIP）盐、舒林酸-哌嗪（SUL-0.5PIP）盐、苯丁唑酮-哌嗪（PBZ-0.5PIP）盐、酮洛芬-哌嗪（KPF-0.5PIP）盐和氟比洛芬-哌嗪（FLB-0.5PIP）盐。通过单晶 X 射线衍射阐述了它们的空间结构、排列、相互作用和缔合。粉末 X 射线衍射、傅里叶变换红外、差示扫描量热法和热重分析用于表征这些新盐。与原料药相比，这六种新盐在纯水中的溶解度提高了 10 倍以上，溶解速度也更快，溶解度的显著提高与盐的结构密切相关。
