温度敏感型20(S)-原人参二醇微乳-凝胶复合给药系统的研究  

Study of thermosensitive 20(S)-Protopanaxadiol microemulsion-gel composite drug delivery system

作　　者：唐逢雨 周欣 尉小慧[1,2] 王峥涛 TANG Fengyu;ZHOU Xin;WEI Xiaohui;WANG Zhengtao(MOE Key Laboratory of Standardization of Chinese Medicine,Institute of Chinese Materia Metlica,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;Shanghai R&D Center for Standardization of Chinese Medicine,Shanghai 201203,China)

机构地区：[1]上海中医药大学中药研究所,中药标准化教育部重点实验室,上海201203 [2]上海中药标准化研究中心,上海201203

出　　处：《上海中医药大学学报》2021年第6期66-72,共7页Academic Journal of Shanghai University of Traditional Chinese Medicine

基　　金：上海市自然科学基金资助项目(18ZR1439500)。

摘　　要：目的:优化温度敏感型20(S)-原人参二醇(PPD)微乳-凝胶复合系统的制备工艺,并对其胶凝温度、胶凝时间、外观性状、流变学、体外释药及机制进行研究。方法:在前期PPD微乳制备工艺基础上,采用冷溶法制备温度敏感型PPD微乳-凝胶复合系统。采用单因素试验考察处方辅料泊洛沙姆407(P407)、羟丙基甲基纤维素(HPMC)、海藻酸钠(SA)和甘油对胶凝温度的影响,确定基本处方;继而以胶凝温度、胶凝时间和体外释放度为评价指标,筛选出最佳处方工艺。采用透射电镜和扫描电镜观察形态学;采用旋转流变仪考察流变学特性;采用透析袋法测定体外释药度,并进行方程拟合,探讨其释药机制。结果:温度敏感型PPD微乳-凝胶复合系统的最佳处方为:30%P407水溶液,P407水溶液与PPD微乳体积比为2∶1,0.6%HPMC,0.2%SA,4%甘油,0.05%尼泊金乙酯。此条件下制得的温度敏感型PPD微乳-凝胶的胶凝温度为(30.9±0.1)℃,胶凝时间为(146.7±4.4)s;扫描电镜下其呈多孔结构,孔隙疏松;透射电镜显示微乳颗粒圆整、无粘连。该制剂具有良好的温度敏感性,室温下流动性良好,在略低于皮肤温度的条件下可以发生从溶液到凝胶的相变过程;体外释放可达72 h,体外释药过程符合Weibull方程,为药物扩散和骨架溶蚀协同作用。结论:所研究的温度敏感型PPD微乳-凝胶复合系统制备工艺简单,胶凝温度、时间适宜,具有温度敏感、缓释特性,可满足皮肤局部用药需求。Objective: To optimize the preparation process of thermosensitive 20(S)-Protopanaxadiol(PPD) microemulsion-gel composite system, and investigate its gelation temperature, gelation time, appearance characteristics, rheology, and drug release in vitro and mechanism. Methods: Based on the preparation process of PPD microemulsion in the previous stage, the thermosensitive PPD microemulsion-gel composite system was prepared by cold-dissolving method. The influence of different excipients on the gelation temperature was investigated by single factor test to determine the basic formula, including poloxamer 407(P407), hydroxypropyl methyl cellulose(HPMC), sodium alginate(SA) and glycerin. Then, the optimal formulation and process of the composite system were selected according to the gelation temperature, gelation time and in vitro release. The morphology was observed by scanning electron microscope(SEM) and transmission electron microscope(TEM). The rheological properties were detected by rotary rheometer. The drug release rate in vitro was determined by dialysis method, and the equations were fitted to explore the drug release mechanism. Results: The optimized formulation of thermosensitive PPD microemulsion-gel composite system was as follows: 30% P407 aqueous solution, 0.6% HPMC, 0.2% SA, 4% glycerol, 0.05% Nipagin ethyl ester, and the volume ratio of P407 aqueous solution to PPD microemulsion was 2∶1. Forthermosensitive PPD microemulsion-gel prepared under this condition, the gelation temperature was(30.9±0.1)℃ and the gelation time was(146.7±4.4) s. SEM showed porous structure and loose pores, and TEM showed that the microemulsion particles were round and without adhesion. The preparation showed good thermosensitivity and good fluidity at room temperature. It could undergo phase transition from solution to gel when slight below skin temperature. The release timein vitrowas 72 hours. The drug release processin vitroconformed to Weibull equation, which was the synergistic effect of drug diffusion and skeleton d

关 键 词：20(S)-原人参二醇 微乳-凝胶复合系统 温度敏感 制备工艺 释药机制 

分 类 号：R943[医药卫生—药剂学]