摘要
为提高姜黄素自纳米乳(CUR-SNEDDS)中药物分散过饱和度和维持时间,引入沉淀抑制剂(PPIs),制备姜黄素过饱和自纳米乳(CUR-SSNEDDS)。通过溶解度试验、油相和表面活性剂的配伍变化、表面活性剂乳化能力的考察以及伪三元相图的绘制,筛选出CUR-SNEDDS处方组成,采用层次分析法结合星点设计-响应面法优化处方。以维持姜黄素(CUR)在人工胃肠液中的过饱和浓度和持续时间筛选沉淀抑制剂(PPIs)类型及用量,同时采用偏光显微镜评估结晶抑制效果,并对CUR-SSNEDDS质量及体外释放行为进行评价。所制备的CUR-SSNEDDS处方为丙二醇单辛酸酯(capryol 90)-聚氧乙烯氢化蓖麻油(kolliphor RH40)-二乙二醇单乙基醚(transcutol HP)-聚乙烯己内酰胺-聚醋酸乙烯酯-聚乙二醇接枝共聚物(Soluplus)(7.93∶66.71∶25.36∶5),载药量为(65.12±1.25)mg·g-1,形成的纳米乳黄色透明,乳滴呈圆球形且分布均匀,乳化时间为(21.02±0.13)s,平均粒径为(57.03±0.35)nm,多分散指数(PDI)为(0.23±0.01),Zeta电位为(-18.10±1.30)mV,CUR-SSNEDDS体外稀释后显著抑制结晶的形成与生长,过饱和度在2 h内可维持在10以上,在人工胃肠液中CUR溶出的速度和程度均显著提高。Soluplus可有效维持过CUR过饱和状态,增强CUR体外溶出。
In order to improve the supersaturation and maintenance time of drug dispersion in curcumin self-nanoemulsion(CUR-SNEDDS), precipitation inhibitors(PPIs) were introduced to prepare curcumin supersaturated self-emulsion(CUR-SSNEDDS). The composition of CUR-SNEDDS prescriptions was selected through the solubility test, the compatibility of oil phase and surfactant, the investigation of the emulsifying ability of the surfactant and the drawing of the pseudo-ternary phase diagram. Analytic hierarchy process was used in combination with central composite design-response surface method to optimize the prescription. The type and dosage of precipitation inhibitors(PPIs) were selected to maintain the supersaturated concentration and duration of CUR in artificial gastrointestinal fluids. At the same time, polarizing microscope was used to evaluate the crystallization inhibition effect and the quality and in vitro release behavior of CUR-SSNEDDS. The prepared CUR-SSNEDDS prescription was capryol 90-kolliphor RH40-transcutol HP-Soluplus(7.93∶66.71∶25.36∶5), with the drug loading of(65.12±1.25) mg·g-1. CUR-SSNEDDS was transparent yellow, and the nanoemulsion droplets were spherical with uniform distribution. The emulsification time was(21.02±0.13) s, the average particle size was(57.03±0.35) nm, the polydispersity index(PDI) was(0.23 ± 0.01), and the Zeta potential was(-18.10±1.30) mV. CUR-SSNEDDS significantly inhibited the generation and growth of crystals after in vitro dilution. The supersaturation could be maintained above 10 within 2 h, and the dissolution rate and degree of CUR in artificial gastrointestinal fluid were significantly increased. Soluplus could effectively maintain the supersaturated state of CUR and enhance CUR dissolution in vitro.
作者
陈绪龙
梁新丽
丁海波
赖章婷
袁其里
林霞
廖正根
CHEN Xu-long;LIANG Xin-li;DING Hai-bo;LAI Zhang-ting;YUAN Qi-li;LIN Xia;LIAO Zheng-gen(Key Laboratory of Mordent Preparation of Traditional Chinese Medicine,Ministry of Education,Jiangxi University of Traditional Chinese Medicine,Nanchang 330004,China)
出处
《中国中药杂志》
CAS
CSCD
北大核心
2020年第15期3672-3680,共9页
China Journal of Chinese Materia Medica
基金
江西省一流学科项目(JXSYLXK-ZHYAO059)
江西省卫生计生委科技计划项目(20181140)。
关键词
姜黄素
过饱和自纳米乳
人工胃肠液
载药量
过饱和度
curcumin
supersaturated self-nanoemulsion
artificial gastrointestinal fluid
drug loading
supersaturation
