钩藤碱纳米混悬剂缓释片制备、优化与体外释放评价  

Rhynchophylline nanosuspensions sustained-release tablets:Preparation,optimization and release evaluation in vitro

作　　者：邓向涛 张文周 张智强[2] DENG Xiang-tao;ZHANG Wen-zhou;ZHANG Zhi-qiang(Affiliated Cancer Hospital of Zhengzhou University,Zhengzhou 450003,China;Tianjin Institute of Pharmaceutical Research Pharmaceutical Co.,Ltd.,Tianjin 300301,China)

机构地区：[1]郑州大学附属肿瘤医院,河南郑州450003 [2]天津药物研究院药业有限责任公司,天津300301

出　　处：《中草药》2020年第20期5128-5136,共9页Chinese Traditional and Herbal Drugs

基　　金：国家科技重大专项(2018ZX09201009-002-009);国家科技重大专项(2017ZX09101007-001-005)。

摘　　要：目的制备钩藤碱纳米混悬剂及其冻干粉,并进一步研制成缓释片。方法微量沉淀法联合高压均质法制备钩藤碱纳米混悬剂,并制备成冻干粉末。测定其粒径及Zeta电位,扫描电子显微镜观察纳米混悬剂外貌形态。采用乳糖作为冻干保护剂,将纳米混悬剂制备成冻干粉末。羟丙基甲基纤维素(hydroxypropyl methyl cellulose,HPMC)作为骨架材料,将钩藤碱纳米混悬剂冻干粉末制备成凝胶骨架缓释片。单因素考察联合设计正交试验得出最佳处方,并进行释药模型拟合。结果钩藤碱纳米混悬剂平均粒径为(153.7±4.9)nm,Zeta电位为(-18.54±1.32)mV,纳米混悬剂外貌为球形或类球形。正交优化后的钩藤碱纳米混悬剂缓释片,在12 h内累积释放率为92.53%。体外释放符合Higuchi释药模型药物释放,释药方程为ln(1-Mt/M∞)=0.2860 t1/2-0.0690(r=0.9924),药物释放为扩散和骨架溶蚀并存。结论钩藤碱纳米混悬剂粒径较小,研制的缓释片可有效控制钩藤碱纳米混悬剂缓释片缓慢释放。Objective To prepare the rhynchophylline nanosuspensions and lyophilized powder,and study its sustained-release tablets.Methods Rhynchophylline nanosuspensions were prepared by microprecipitation combined with high pressure homogenization method,and the particle size and zeta potential were determined.Scanning electron microscopy(SEM)was employed to observe the appearances of nanosuspensions.Nanosuspensions were prepared into lyophilized powder using lactose as freeze-dried protectors.HPMC(hydroxypropyl methyl cellulose)was used as hydrophilic matrix to prepare the sustained-release tablets.Single factor investigation and orthogonal experiments were employed to optimize the formulation of rhynchophylline nanosuspensions sustained-release tablets,and the model fitting was also been studied.Results The particle size and zeta potential of rhynchophylline nanosuspensions were(153.7±4.9)nm and(-18.54±1.32)mV,respectively.The appearances of rhynchophylline nanosuspensions were spherical or nearly spherical.After orthogonal optimization,the cumulative release rate of rhynchophylline nanosuspensions sustained-release tablets was 92.53%in 12 h.The optimized formulation of hydrogel matrix sustained-release tablets was better accorded with Higuchi model:ln(1-Mt/M∞)=0.2860 t1/2-0.0690(r=0.9924).The drug release from hydrogel matrix sustained-release tablets were controlled by diffusion and degradation.Conclusion The obtained rhynchophylline nanosuspensions has small particle size.The prepared hydrogel matrix sustained-release tablets can control the release of rhynchophylline nanosuspensions in a slow characteristic.

关 键 词：钩藤碱 纳米混悬剂 溶解度 累积释放率 缓释片 冻干粉 微量沉淀法 高压均质法 羟丙基甲基纤维素 正交试验 Higuchi释药模型 扩散 骨架溶蚀 

分 类 号：R283.6[医药卫生—中药学]