摘要
目的:制备黄豆苷元纳米混悬剂胶囊,以市售黄豆苷元胶囊为参考,考察两者对小肠吸收与口服生物利用度的影响。方法:采用沉淀法联用高压均质技术制备黄豆苷元纳米混悬剂,通过正交试验优化其处方,利用X射线粉末衍射分析(XRPD),傅里叶红外光谱(FT-IR),透射电子显微镜(TEM)以及粒径,多分散指数和Zeta电位等指标对黄豆苷元纳米混悬剂进行表征。采用外翻肠囊法研究自制制剂与市售黄豆苷元胶囊的体外肠吸收情况,考察了黄豆苷元纳米混悬剂在体内胃肠道的分布,并通过HPLC测定大鼠体内黄豆苷元的血药浓度,以考察口服给药后的生物利用度。结果:以市售黄豆苷元胶囊内容物为参比制剂,自制黄豆苷元纳米混悬剂胶囊的小肠吸收促进率2. 49(P <0. 01),胃肠道生物分布评价证实了纳米混悬液的生物黏附性,相对生物利用度294%。结论:沉淀法联用高压均质技术制备的黄豆苷元纳米混悬剂冻干后可用于胶囊剂等剂型的生产,有益于增加药物的小肠吸收并改善口服以后的体内生物利用度。
Objective: To prepare daidzein nanosuspension capsules, and to investigate intestinal absorption and oral bioavailability by comparing with commercial daidzein capsules. Method: Daidzein nanosuspensions were prepared by precipitation method combined with high pressure homogenization,orthogonal design method was utilized to optimize its formulation. Daidzein nanosuspensions was characterized by X-ray powder diffraction( XRPD),Fourier transform infrared spectroscopy( FT-IR),transmission electron microscope( TEM),and indexes including mean particle size,polydispersity index( PDI),and Zeta potential. Intestinal absorption study was carried out to compare the accumulative permeated amount of daidzein from daidzein nanosuspensions and commercial daidzein capsules. Biodistribution of daidzein in gastrointestinal tract was investigated,and oral bioavailability was examined through pharmacokinetic study by HPLC. Result: The in vitro small intestinal absorption enhancement ratio of daidzein nanosuspension capsules was approximately 2. 49-fold higher than that of commercial capsules( P < 0. 01). Biodistribution evaluation in gastrointestinal tract verified the bioadhesion of the nanosuspensions. Pharmacokinetic study calculated by DAS 2. 0 revealed that the relative bioavailability of daidzein nanosuspension capsules was 294%. Conclusion: Daidzein nanosuspensions prepared by combined method can be applied to the production of capsules,which is beneficial to increase the absorption of drug in small intestine and improve its bioavailability after oral administration.
作者
杨晓茗
黄尊
张君
左甜甜
沈琦
YANG Xiao-ming;HUANG Zun;ZHANG Jun;ZUO Tian-tian;SHEN Qi(School of Pharmacy,Shanghai Jiaotong University,Shanghai 200240,China)
出处
《中国实验方剂学杂志》
CAS
CSCD
北大核心
2019年第2期40-47,共8页
Chinese Journal of Experimental Traditional Medical Formulae
关键词
黄豆苷元
纳米混悬剂
胶囊
高压均质技术
体外肠吸收
药代动力学
生物利用度
daidzein
nanosuspensions
capsules
high pressure homogenization technology
in vitro intestinal absorption
pharmacokinetics
bioavailability
作者简介
第一作者:杨晓茗,在读硕士,从事纳米制剂研究,E-mail:miny@sjtu.edu.cng;通信作者:沈琦,博士,教授,从事纳米制剂研究,Tel:021-34204049,E-mail:qshen@sjtu.edu.cn.
