Li Ying, Yang Da-Jian, Chen Shi-Lin, Chen Si-Bao, Chan Albert Sun-Chi
Shanghai Jiao Tong University, Shanghai, PR China.
Pharm Res. 2008 Mar;25(3):563-77. doi: 10.1007/s11095-007-9418-x. Epub 2007 Sep 8.
The aim of this work was to compare the physicochemical characteristics of the phospholipids complex of puerarin (Pur) prepared by traditional methods (solvent evaporation, freeze-drying and micronization) and a supercritical fluid (SCF) technology. The physicochemical properties of the pure drug and the corresponding products prepared by two different SCF methods were also compared.
Solid-state characterization of particles included differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), solubility, dissolution rate and scanning electron microscopy (SEM) examinations. Besides puerarin phospholipids complex (PPC) by four different methods, the solid-state properties of unprocessed, gas antisolvent (GAS) crystallized and solution enhanced dispersion by supercritical fluid (SEDS) precipitated puerarin samples were also compared. Crystallinity was assessed using DSC and XRPD. Drug-phospholipids interactions were characterized using Fourier transform infrared spectroscopy (FTIR). SEM was used to determine any morphological changes. Pharmaceutical performance was assessed in dissolution rate and solubility tests.
The results of the physical characterization attested a substantial correspondence of the solid state of the drug before and after treatment with GAS technique, whereas a pronounced change in size and morphology of the drug crystals was noticed. The GAS-processed puerarin exhibited a better crystal shape confirmed by DSC, XRPD and IR. Polymorphic change of puerarin during SEDS coupled with the dramatic reduction of the dimensions determined a remarkable enhancement of its solubility and in vitro dissolution rate. Phospholipids complex prepared using supercritical fluid technology showed similar properties of physical state, thermal stability and molecular interaction with phospholipids (PC) to those of corresponding systems prepared by other three conventional methods namely solvent evaporation, freeze-drying and micronization as proved by XRPD, DSC, and FTIR. The best dissolution rate was obtained by SEDS-prepared complex, while the highest solubility was obtained for solvent evaporation method.
Supercritical fluid technology for the preparation of puerarin and its phospholipids complex has been proven to have significant advantages over the solvent evaporation technique and other conventional methods.
本研究旨在比较采用传统方法（溶剂蒸发法、冷冻干燥法和微粉化法）以及超临界流体（SCF）技术制备的葛根素（Pur）磷脂复合物的理化特性。同时，还比较了纯药物以及通过两种不同SCF方法制备的相应产品的理化性质。
颗粒的固态表征包括差示扫描量热法（DSC）、X射线粉末衍射（XRPD）、溶解度、溶出速率和扫描电子显微镜（SEM）检查。除了通过四种不同方法制备的葛根素磷脂复合物（PPC）外，还比较了未处理的、气体抗溶剂（GAS）结晶的以及超临界流体溶液增强分散（SEDS）沉淀的葛根素样品的固态性质。使用DSC和XRPD评估结晶度。使用傅里叶变换红外光谱（FTIR）表征药物与磷脂的相互作用。使用SEM确定任何形态变化。通过溶出速率和溶解度测试评估药物性能。
物理表征结果证明，GAS技术处理前后药物的固态基本一致，但药物晶体的尺寸和形态发生了明显变化。DSC、XRPD和IR证实，GAS处理的葛根素呈现出更好的晶体形状。SEDS过程中葛根素的多晶型变化以及尺寸的显著减小导致其溶解度和体外溶出速率显著提高。XRPD、DSC和FTIR证明，使用超临界流体技术制备的磷脂复合物与通过溶剂蒸发法、冷冻干燥法和微粉化法这三种传统方法制备的相应体系相比，在物理状态、热稳定性以及与磷脂（PC）的分子相互作用方面具有相似的性质。SEDS制备的复合物溶出速率最佳，而溶剂蒸发法获得的溶解度最高。
已证明，超临界流体技术制备葛根素及其磷脂复合物比溶剂蒸发技术和其他传统方法具有显著优势。
