姜黄色素-共聚维酮共研磨粉体性质及溶出度研究  

Properties and dissolution of curcumin-PVP co-grinding powder

作　　者：李淑坤 汪晶[1,2,3] 仝萌 于翔羽 胡子奇 黄一平[1,2,3] 张振海[1,2,3] LI Shu-kun;WANG Jing;TONG Meng;YU Xiang-yu;HU Zi-qi;HUANG Yi-ping;ZHANGZhen-hai(Affiliated Hospital of Integrated Traditional Chinese and Western Medicine,Nanjing University of Chinese Medicine,Nanjing 210028,China;Key Laboratory of New Drug Delivery System of Chinese Materia Medica,Jiangsu Province Academy of Chinese Medicine,Nanjing 210028,China;Nanjing University of Chinese Medicine,Nanjing 210028,China)

机构地区：[1]南京中医药大学附属中西医结合医院,江苏南京210028 [2]国家中医药管理局中药释药系统重点研究室,江苏省中医药研究院,江苏南京210028 [3]南京中医药大学,江苏南京210028

出　　处：《中草药》2020年第23期5949-5955,共7页Chinese Traditional and Herbal Drugs

基　　金：国家自然科学基金资助项目(81803756);江苏省六大人才高峰计划(SWYY-010);江苏省中医药研究院自主科研项目(BM2018024-2019006);江苏省重点学科组分中药工程学(ZDXK003)。

摘　　要：目的以姜黄色素为模型药物,考察辅料共聚维酮在共研磨过程中的应用特性及共研磨产物提高难溶性药物姜黄色素体外溶出方面的可行性。方法采用共研磨法,在姜黄色素粉末中分别加入0%、1%、3%共聚维酮,制成不同比例的共研磨物,通过激光粒度仪及扫描电子显微镜(SEM)对其粒径形态进行考察;运用差示扫描量热法(DSC)、SEM和X射线粉末衍射法(XRPD)鉴别药物在共研磨物中的物相状态;测定姜黄色素原料药、物理混合物和共研磨物在2种溶出介质中的体外溶出度,并考察其加速稳定性。结果与原料药相比,共聚维酮共研磨物粉末粒径减小,吸湿性和DSC无明显变化;XRPD中姜黄色素主要峰强度有所减弱,结晶度降低;共研磨物中姜黄色素的主要成分溶出度显著提高,在加速条件下放置3个月后溶出未发生变化,稳定性较好。结论共聚维酮作为新型辅料,其与姜黄色素共研磨后得到的产物能有效改善难溶性药物姜黄色素的溶出度,且稳定性较好;为提高难溶性药物的溶解度和口服生物利用度提供了一种可行的策略。Objective To investigate the application characteristics of excipient copovidone in co-grinding process and the feasibility of co-grinding products for improving the dissolution of curcumin, using curcumin as a model drug in vitro. Methods The prepared products were obtained by curcumin and various proportions(0%, 1%, 3%) of copovidone in co-grinding process, which were characterized by laser particle size analyzer, differential scanning calorimetry(DSC), scanning electron microscopy(SEM), and X-ray powder diffraction(XRPD). The in vitro dissolution of milled products was evaluated in two media, and their accelerated stability was investigated. Results In comparison with pure curcumin, the particle size of milled products decreased with the lower crystallinity by XRPD analysis, but the hygroscopicity and DSC thermograms showed no significant difference. Moreover, compared with pure curcumin, the products exhibited significant improvement of in vitro dissolution. Also, there was no significant difference in the dissolution behavior of products placed under the accelerated conditions(40 ℃, RH 75%) for three months, indicating their good stability. Conclusion As a new excipient, copovidone could effectively enhance the dissolution of curcumin via co-grinding process. This study provided a feasible strategy for improving the solubility and even oral bioavailability of poorly soluble drugs.

关 键 词：姜黄色素 共聚维酮 共研磨法 体外溶出 稳定性 加速稳定性 吸湿性 

分 类 号：R283.6[医药卫生—中药学]