苦豆碱阴道用温敏凝胶的流变学及释药行为研究  

Rheological properties and release profile of aloperine vaginal thermosensitive in situ gel

作　　者：张涓[1] 许嘉辉 赵晨熙 刘聪 刘松涛 唐嘉豪 李婷 ZHANG Juan;XU Jiahui;ZHAO Chenxi;LIU Cong;LIU Songtao;TANG Jiahao;LI Ting(College of Pharmacy,Shaanxi University of Chinese Medicine,Xianyang,Shaanxi,712046 P.R.China;First Clinical Medical College,Shaanxi University of Chinese Medicine,Xianyang,Shaanxi,712046 P.R.China)

机构地区：[1]陕西中医药大学药学院,陕西咸阳712046 [2]陕西中医药大学第一临床医学院,陕西咸阳712046

出　　处：《华西药学杂志》2024年第5期527-532,共6页West China Journal of Pharmaceutical Sciences

基　　金：陕西省科技厅社发攻关项目(2023-YBSF-378);陕西省2022年省级大学生创新训练计划项目(S202210716043)。

摘　　要：目的考察苦豆碱阴道用温敏原位凝胶的流变学性质,并预测其体内释放行为。方法采用冷溶法工艺,以泊洛沙姆407和泊洛沙姆188为材料制备温敏凝胶;倒置法检测苦豆碱温敏凝胶的胶凝温度和时间;流变仪测定流变学参数;采用无膜溶出模型评价体外释药性能;荧光成像法考察阴道局部滞留性。结果凝胶剂在室温下为淡黄色、均匀、透明的流体,黏度较低;在约33℃变为凝胶状假塑性流体,黏度上升;且经阴道模拟液稀释后,在37℃仍能形成凝胶。凝胶中苦豆碱的体外释放动力学行为符合Higuchi方程。通过成像与IR783荧光定量分析可知:苦豆碱温敏凝胶在小鼠阴道内至少可停留48 h,但其溶液剂在24 h时几乎观察不到荧光信号。结论苦豆碱温敏凝胶具适宜的胶凝温度和良好的流变学性质,可延长药物在阴道内的滞留时间,延缓药物的释放,能满足阴道局部用药的要求。OBJECTIVE To examine the rheological characteristics of a thermosensitive in situ gel containing aloperine for vaginal application and to forecast its in vivo release pattern.METHODS The thermosensitive gel was fabricated using poloxamer 407 and poloxamer 188 through a cold dissolution process.The gelation temperature and duration of the aloperine thermosensitive gel were determined using the inverted tube method.Rheological parameters were measured with a rheometer,and the in vitro drug release performance was assessed using a membraneless dissolution model.The local retention in the vagina was studied using fluorescence imaging.RESULTS The gel at room temperature appeared as a light yellow,homogeneous,transparent fluid with low viscosity.It transformed into a gel-like pseudoplastic fluid with increased viscosity at approximately 33℃and formed a gel at 37℃after being diluted with a simulated vaginal fluid.The in vitro release kinetics of aloperine from the thermosensitive gel aligned with the Higuchi equation.Through imaging and IR783 fluorescence quantitative analysis,the aloperine thermosensitive gel could remain in the mouse vagina for at least 48 h,with almost no fluorescence signal observable in its solution after 24 h.CONCLUSION Aloperine thermosensitive gel,with its appropriate gelation temperature and excellent rheological properties,has the potential to extend the drug retention time in the vagina and delay drug release,thereby meeting the requirements for local vaginal medication.

关 键 词：苦豆碱 阴道给药 温敏凝胶 流变学 体外释放度 无膜溶蚀 局部滞留性 

分 类 号：R94[医药卫生—药剂学] R917[医药卫生—药学]