An innovative rhein-matrine cocrystal: Synthesis, characterization,formation mechanism and pharmacokinetic study  

作　　者：Hongjuan Wang Dezhi Yang Wen Zhang Junke Song Ningbo Gong Mingchao Yu Shiying Yang Baoxi Zhang Qiwen Liu Guanhua Du Yang Lu 

机构地区：[1]Beijing Key Laboratory of Polymorphic Drugs,Center of Pharmaceutical Polymorphs,Institute of Materia Medica,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100050,China [2]Beijing Key Laboratory of Drug Targets Identification and Drug Screening,National Center for Pharmaceutical Screening,Institute of Materia Medica,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100050,China

出　　处：《Chinese Chemical Letters》2023年第2期546-549,共4页中国化学快报（英文版）

基　　金：supported by Drug Innovation Major Project (Nos. 2018ZX09711001–001–015, 2018ZX09711001–003– 022);CAMS Innovation Fund for Medical Sciences (No. 2016I2M-3–007)。

摘　　要：Rhein(Rhe), an anthraquinone derivative, exhibits excellent anti-inflammatory effects and other pharmacological activities, but its clinical application remains limited due to poor solubility. The present work aims at the improvement of solubility and oral bioavailability of Rhe through cocrystal formation. For this purpose, Rhe and matrine(Mat) were selected as pharmaceutical ingredient(API) and cocrystal former(CCF), respectively, and the Rhe-Mat cocrystal was synthesized and characterized by single crystal X-ray diffraction(SXRD), powder X-ray diffraction(PXRD), thermogravimetric analysis(TGA), differential scanning calorimetry(DSC). The formation mechanism of Rhe-Mat cocrystal was elucidated by molecular surface electrostatic potential(MSEP). It is worth mentioning that the 50-fold increment of dissolution in vitro was observed in pure water in the form of Rhe-Mat cocrystal. Furthermore, the in vivo studies revealed that Rhe-Mat cocrystal indicated the faster absorption rate and the higher peak blood concentration than the pure Rhe. Hence, it can be concluded that current study successfully improved the solubility and oral bioavailability of Rhe.

关 键 词：RHEIN MATRINE COCRYSTAL Poor solubility Molecular surface electrostatic potential 

分 类 号：R285[医药卫生—中药学] TQ460.1[医药卫生—中医学]