Insight into the Phase Transformation among Various Solid Forms of Baicalein

A new polymorph and three hydrates
of baicalein, a widely prescribed
anti-inflammatory TCM drug, were discovered through comprehensive
polymorph screening experiments. The forms were fully characterized
by a range of analytical techniques, including PXRD, Raman spectra,
FTIR, HSM, SEM, TGA, DSC, and DVS. Single crystal structures and the
transformation pathways among different polymorphs and hydrates are
discussed in detail. Single-crystal-to-single-crystal transformation
behavior between monohydrate and hemihydrate was revealed. Thermodynamic
stability, hygroscopicity, and powder dissolution behavior were investigated.
The results show that the newly discovered form γ presents better
dissolution behavior and remarkably greater apparent solubility compared
with the current widely used marketed drug substance.

本研究通过全面的晶型筛选实验，发现了临床广泛应用的抗炎类中医药(TCM)药物黄芩素(baicalein)的1种新型多晶型与3种水合物。上述多晶型与水合物通过一系列分析技术完成了完整表征，涵盖粉末X射线衍射(PXRD, Powder X-ray Diffraction)、拉曼光谱、傅里叶变换红外光谱(FTIR, Fourier Transform Infrared Spectroscopy)、热台显微镜(HSM, Hot Stage Microscopy)、扫描电子显微镜(SEM, Scanning Electron Microscopy)、热重分析(TGA, Thermogravimetric Analysis)、差示扫描量热法(DSC, Differential Scanning Calorimetry)以及动态蒸汽吸附(DVS, Dynamic Vapor Sorption)。本研究详细阐述了单晶结构以及不同多晶型与水合物之间的转化路径，并揭示了一水合物与半水合物之间的单晶-单晶转化行为。此外，本研究还考察了该系列样品的热力学稳定性、吸湿性与粉末溶出行为。研究结果表明，新发现的γ型多晶型相较于当前广泛使用的市售原料药，具备更优异的溶出性能以及显著更高的表观溶解度。