返回 
加入收藏
共载小檗碱/胡椒碱自微乳给药系统的构建及评价
x
请在关注微信后，向客服人员索取文件
| 篇名： | 共载小檗碱/胡椒碱自微乳给药系统的构建及评价 |
| TITLE： | Construction and evaluation of berberine/piperine co-loaded self-microemulsion drug delivery system |
| 摘要： | 目的 制备共载小檗碱/胡椒碱自微乳给药系统（BBR/PIP-SMEDDS），评价其理化性质、体外释药及药动学特征。方法通过外翻肠囊法确定制剂中小檗碱（BBR）和胡椒碱（PIP）的载药质量比；通过溶解度检测、相容性评价和伪三元相图分别确定油相、乳化剂和助乳化剂；以油相用量、乳化剂-助乳化剂质量比为因素，粒径和Zeta电位的综合评分为响应值，采用星点设计-效应面法优化空白自微乳给药系统（SMEDDS）的处方并验证；按最优处方，在磁力搅拌下加入过量BBR、PIP原料药，制得BBR/PIP-SMEDDS，对其理化性质、体外释药行为、大鼠体内药动学特征进行考察。结果BBR和PIP的载药质量比为1∶1，最优处方为油相（油酸乙酯）占18.54%，乳化剂（吐温-80）占52.16%，助乳化剂（聚乙二醇400）占29.30%。3次验证实验显示，所得空白SMEDDS的平均粒径为（16.49±0.49）nm，Zeta电位为（－16.22±0.77）mV，综合评分为0.97分，与预测值（0.95分）的相对偏差为2.11%。所制BBR/PIP-SMEDDS为水包油型微乳，为金黄色油状液体，呈圆球状，平均粒径为（32.90±0.38）nm，Zeta电位为（－19.17±0.70）mV；BBR的包封率为（90.44±0.88）%，载药量为（10.18±0.17）mg/g；PIP的包封率为（87.48±1.13）%，载药量为（9.41±0.17）mg/g（n＝3）。BBR/PIP-SMEDDS低温（4℃）避光、离心、稀释条件下稳定性较好。体外释药结果显示，制备成SMEDDS后，BBR在模拟肠液中24h时的累积释放百分率明显高于原料药。大鼠药动学研究结果表明，BBR/PIP-SMEDDS的峰浓度、药时曲线下面积（AUC0－）t分别是原料药的4.61、7.07倍，相对生物利用度为707.484%。结论成功制得BBR/PIP-SMEDDS，所得制剂的体外释放和生物利用度均较原料药有较大提升。 |
| ABSTRACT： | OBJECTIVE To prepare berberine/piperine co-loaded self-microemulsion drug delivery system （BBR/PIP- SMEDDS）， evaluate its physicochemical properties， in vitro release and pharmacokinetic characteristics. METHODS The drug loading mass ratio of berberine （BBR） and piperine （PIP） in the preparation was determined by the everted intestinal sac method. The oil-phase， emulsifier and co-emulsifier were determined by solubility detection， compatibility evaluation and pseudo-ternary phase diagram， respectively. The formulation of blank self-microemulsion drug delivery system （SMEDDS） was optimized and verified by central composite design-response surface methodology with the amount of oil-phase and the mass ratio of emulsifier to co-emulsifier as factors， and the comprehensive score of particle size and Zeta potential as response value. According to the optimal prescription， BBR/PIP-SMEDDS was prepared by adding excessive BBR and PIP raw materials under magnetic stirring， and its physicochemical properties， in vitro release behavior and pharmacokinetic characteristics in rats were investigated. RESULTS The drug loading mass ratio of BBR and PIP was 1∶1. The optimal prescription included oil-phase （ethyl oleate） accounted for 18.54%， emulsifier （Tween-80） accounted for 52.16%， and co-emulsifier （polyethylene glycol 400） accounted for 29.30%. Three verification experiments showed that the average particle size of blank SMEDDS was （16.49±0.49） nm； the Zeta potential was （－16.22±0.77） mV； the comprehensive score was 0.97， the relative deviation of which from the predicted value （0.95） was 2.11%. The prepared BBR/PIP-SMEDDS was an oil-in-water microemulsion， which was a golden yellow oily liquid with a spherical shape. The average particle size was （32.90±0.38） nm， and the Zeta potential was （－19.17±0.70） mV. The encapsulation efficiency of BBR was （90.44±0.88）% ， and the drug loading was （10.18±0.17） mg/g. The encapsulation efficiency of PIP was （87.48±1.13）%， and the drug loading was （9.41±0.17） mg/g. BBR/PIP-SMEDDS had good stability at low temperature （4 ℃ ） in the dark， centri-fugation and dilution. The results of in vitro release showed that the cumulative release percentage of BBR in simulated intestinal fluid for 24 h was significantly higher than that of the raw drug after the preparation of SMEDDS. The pharmacokinetic results in rats showed that the peak concentration and area under the drug- concentration time curve （AUC0－）t of BBR/PIP-SMEDDS were 4.61 and 7.07 times higher than those of the raw drug respectively， and the relative bioavailability was 707.484%. CONCLUSIONS BBR/PIP-SMEDDS is successfully prepared， and the in vitro release and bioavailability of the preparation are greatly improved compared with the raw material. |
| 期刊： | 2024年第35卷第24期 |
| 作者： | 李春梅；刘佳雯；张馨元；周长胜 |
| AUTHORS： | LI Chunmei，LIU Jiawen，ZHANG Xinyuan，ZHOU Changsheng |
| 关键字： | 小檗碱；胡椒碱；自微乳给药系统；处方优化；理化性质；体外释药；药动学 |
| KEYWORDS： | berberine； piperine； self-microemulsion drug delivery system； preparation optimization； physicochemical |
| 阅读数： | 7 次 |
| 本月下载数： | 0 次 |
* 注：未经本站明确许可，任何网站不得非法盗链资源下载连接及抄袭本站原创内容资源!在此感谢您的支持与合作！
