基于低共熔溶剂的灯盏花素固体分散体的制备  

Preparation of scutellarin solid dispersion based on deep eutectic solvents

作　　者：刘永静[1] 楼丽 黄冬霆 陈丽蓉 王晓颖[1] LIU Yong-jing;LOU Li;HUANG Dong-ting;CHEN Li-rong;WANG Xiao-ying(College of Pharmacy,Fujian University of Traditional Chinese Medicine,Fuzhou 350122,China)

机构地区：[1]福建中医药大学药学院,福建福州350122

出　　处：《药学学报》2024年第9期2665-2672,共8页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金青年基金资助项目(81903928).

摘　　要：本研究以低共熔溶剂(deepeutectic solvents,DESs)作为辅料,进行灯盏花素固体分散体(soliddispersion,SD)的制备研究。采用熔融法制备灯盏花素SD,以累积溶出度为指标,通过单因素试验考察载体材料、DESs种类及载体、DESs、药物的比例等条件,确定最佳制备工艺是:泊洛沙姆407为载体材料,PEG200/脲(2:1)为DESs体系,载体、DESs及药物的比例为6:1:1。在此条件下,所制备的灯盏花素SD的载药量为12.53%,并对灯盏花素SD进行了表征;其次,通过高温、高湿、强光试验评价灯盏花素SD的稳定性,SD中灯盏花素的累积溶出度及含量在高温、高湿及强光条件下均随着时间增加而下降,其中光照对稳定性影响较小;最后,对灯盏花素DESs-SD进行大鼠口服药代动力学研究,动物实验经福建中医药大学实验动物伦理委员会批准(批准号:FJTCMIACUC2023048)。结果表明,将DESs作为制备SD的辅料可以增加灯盏花素口服后的血药浓度,有利于灯盏花素的口服吸收。本研究为在水溶性差的中药活性成分的制剂及增加其口服生物利用度方面提供新的解决方案及研究思路。In this study,deep eutectic solvents(DESs)were used as excipients to prepare solid dispersion(SD)of scutellarin.The SD of scutellarin were prepared by melting method with cumulative dissolution rate as the index of investigation.The preparation conditions of SD of scutellarin were optimized by single factor experiment,which investigated the type of the carrier material,the type of DESs,and the ratio of the drug to the carrier.The optimum preparation conditions of DESs-SD were as follows:using Poloxamer 407 as the carrier material,PEG 200/urea(2:1)as the DESs system,and the ratio of carrier,DESs,and drug was 6:1:1.The drug loading capacity of scutellarin in SD was 12.53%under the optimum preparation conditions.Differential scanning calorimetry,Fourier transform infrared spectroscopy,X-ray powder diffraction and scanning electron microscope exhibited that scutellarin was amorphous form in the SD system.Furthermore,the stability of the DESs-based SD of scutellarin was evaluated by high temperature,high humidity,and strong light tests,which showed that the cumulative dissolution rate and scutellarin content of SD decreased with time under these conditions.Finally,the result of pharmacokinetic studies indicated that the oral absorption of the scutellarin could be increased using DESs as an excipient in the preparation of SD.The animal experiment was approved by the Experimental Animal Ethics Committee of Fujian University of Traditional Chinese Medicine(approval number:FJTCMIACUC 2023048).Consequently,this research offers a novel and effective approach for using DESs to enhance the oral bioavailability of active substances with low water solubility.

关 键 词：低共熔溶剂 灯盏花素 固体分散体 溶出度 药代动力学研究 

分 类 号：R943[医药卫生—药剂学]