利用热熔挤出技术制备和表征白藜芦醇缓释固体分散体  

The preparation and characterization of sustained-release solid dispersion of resveratrol by hot-melt extrusion technology

作　　者：高美琪 吴佳丽[1] 朱文静 张晓彤 樊文玲[1,2] Meiqi Gao;Jiali Wu;Wenjing Zhu;Xiaotong Zhang;Wenling Fan(College of Pharmacy,Nanjing University of Chinese Medicine,Nanjing 210023,China;Jiangsu Provincial Technology Engineering Research Center of TCM Health Preservation,Nanjing 210023,China)

机构地区：[1]南京中医药大学药学院,江苏南京210023 [2]江苏省中医药健康养生技术工程研究中心,江苏南京210023

出　　处：《Journal of Chinese Pharmaceutical Sciences》2023年第3期165-179,共15页中国药学（英文版）

基　　金：The Jiangsu Postgraduate Research Practice Inn ovation Program (Grant No. BK20161403);the 55^(th) Postdoctoral Project (Grant No. 021062001001)。

摘　　要：本文旨在制备、表征和评价固体分散体对低溶解度和高熔点的白藜芦醇(RES)的能力。采用热熔挤出法(HME)制备缓释固体分散体(SRSD),使用疏水-亲水聚合物混合物(EudragitRS和Poloxamer188)控制RES的释放。使用单因素试验系统研究了配方和工艺参数对制备工艺的影响。接着,采用Box-Behnken设计(三因素、三水平)对SRSD的制备工艺进行优化。使用差示扫描量热法和X-射线衍射来确定固体分散体的物理状态,使用扫描电子显微镜观察其表面特性,使用傅里叶红外光谱探寻辅料之间的化学相互作用。通过溶出度试验考察其动力学和释药时间。体外研究表明,制备出的白藜芦醇固体分散体的释放遵循Weibull模型。最终使用热熔挤出技术成功制备了白藜芦醇缓释固体分散物(RESRS P188-SRSD),其中药物与载体的质量比为1:3,释放调节剂为P188,剂量为10%。该制剂稳定性好,溶出度提高了10倍。In the present study,we aimed to prepare,characterize,and evaluate the capability of solid dispersion(SD)for resveratrol(RES)with low solubility and high melting points.A sustained-release solid dispersion(SRSD)was prepared by hot melt extrusion(HME).The release of RES was controlled using a hydrophobic-hydrophilic polymer mixture(Eudragit RS and Poloxamer 188).The effects of formula and process parameters were systematically studied by univariate analysis.Then the Box-Behnken design(three factors,three levels)was used to optimize the preparation process of SRSD.Differential scanning calorimetry and X-ray diffraction were adopted to determine the physical state of SD.Scanning electron microscopy was used to observe its surface properties,and Fourier transform infrared spectroscopy was used to explore chemical interactions between excipients.Dissolution studies were carried out to investigate the kinetics and drug release time.In vitro studies showed that RES release followed the Weibull model kinetic.RES SRSD(RESRS P188-SRSD)was successfully prepared using HME,in which the mass ratio of the drug to the carrier was 1:3,the release regulator was P188,and the dosage was 10%.The stability of the preparation was good,and the dissolution was increased by 10 times.

关 键 词：缓释固体分散体 白藜芦醇 热熔挤出 响应面设计 

分 类 号：R943[医药卫生—药剂学]