以泊洛沙姆188或聚乙二醇8000为载体制备槲皮素晶体分散体系的表征及体外溶出行为研究  

Characterization and dissolution behavior of quercetin crystal dispersion systems prepared with poloxamer 188 or polyethylene glycol 8000 as carriers

作　　者：闫秋丽 章勇 刘耀 胡春晖 严海英 YAN Qiuli;ZHANG Yong;LIU Yao;HU Chunhui;YAN Haiying(Medical College of Qinghai University,Xining 810001,China;State Key Laboratory of Plateau Ecology and Agriculture,Xining 810016,China)

机构地区：[1]青海大学医学部,青海西宁810001 [2]三江源生态与高原农牧业国家重点实验室,青海西宁810016

出　　处：《药物评价研究》2023年第1期100-107,共8页Drug Evaluation Research

基　　金：国家自然科学基金资助项目(82060644);青海省科技厅项目资助(2022-ZJ-748)。

摘　　要：目的制备不同高分子材料的槲皮素(QUR)结晶固体分散体(QUR-CSD),探讨高分子材料对QUR-CSD体外溶出行为的影响及其可能的分子机制。方法分别以泊洛沙姆188(P188)或聚乙二醇8000(PEG8000)为载体,QUR为模型药物,采用旋转蒸发法制备2种QUR-CSD(CSD-P188-QUR、CSD-PEG-QUR)。扫描电子显微镜(SEM)观察样品的微观结构;粉末X-射线衍射法(PXRD)观察晶体学特性;差示扫描量热法(DSC)测定起始熔融温度(T_(c,onset));通过粉末溶出、本征溶出、片剂pH转换溶出实验考察体外溶出行为。结果CSD表征结果显示,2种QUR-CSD中QUR均以结晶态存在,晶体粒径、晶畴尺寸和结晶度均较原料药有所减小,且以P188为载体的CSD对药物上述性质的影响更明显。3种不同的体外溶出实验结果均显示CSD-P188-QUR溶出行为最佳,其次是CSD-PEG-QUR,QUR最差。结论2种高分子材料均可通过影响CSD中QUR的微观结构来改善其体外溶出行为,且以P188为载体的CSD对药物微观结构的影响更为显著。Objective To prepare quercetin(QUR)crystalline solid dispersions(QUR-CSD)with different polymer materials,and to investigate the effect of polymer materials on the dissolution behavior of QUR-CSD in vitro.Method Using poloxamer 188(P188)or polyethylene glycol 8000(PEG8000)as carriers,and QUR as a model drug,two kinds of QUR-CSD(CSD-P188-QUR and CSDPEG-QUR)were prepared by rotary evaporation method.Scanning electron microscope(SEM)was used to observe the microstructure of the sample.The crystallographic properties were observed by powder X-ray diffraction(PXRD).Onset temperature(T_(c,onset))was determined by differential scanning calorimetry(DSC).The dissolution behavior in vitro was investigated by powder dissolution,intrinsic dissolution and tablet pH conversion dissolution tests.Results The CSD characterization results showed that QUR existed in the crystalline state in both preparations,and the crystal particle size,crystal domain size and crystallinity were all reduced comparison with API.The effect of CSD with P188 as carrier on the above properties was more significant.The three different dissolution experiments in vitro showed that CSD-P188-QUR had the best dissolution behavior,followed by CSD-PEG-QUR,and QUR was the worst.Conclusion Both polymer can improve the dissolution behavior by affecting the microstructure of QUR in CSD,and the CSD-P188-QUR has a more significant effect on the microstructure of the drug.

关 键 词：槲皮素 结晶固体分散体 泊洛沙姆 聚乙二醇 体外溶出度 

分 类 号：R283.6[医药卫生—中药学]