Improved dissolution and oral absorption by co-grinding active drug probucol and ternary stabilizers mixtures with planetary beads-milling method

作     者：Fang Li Linsen Li Shaoning Wang Yan Yang Jia Li Dongchun Liu Sijie Zhang Siling Wang Hui Xu 

作者机构：School of PharmacyShenyang Pharmaceutical UniversityBenxi 117004China Shenyang Medical CollegeShenyang 110031China School of Pharmaceutical EngineeringShenyang Pharmaceutical UniversityBenxi 117004China School of Traditional Chinese MedicineShenyang Pharmaceutical UniversityBenxi 117004China 

出 版 物：《Asian Journal of Pharmaceutical Sciences》 (亚洲药物制剂科学（英文）)

年 卷 期：2019年第14卷第6期

页      面：649-657页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 1002[医学-临床医学] 08[工学] 0805[工学-材料科学与工程（可授工学、理学学位）] 080502[工学-材料学] 

基　　金：financial support from the National Basic Research Program of China(973 Program No.2009CB930300) 

主　　题：Probucol Nanosuspension Ternary stabilizers systems Planetary beads-milling Bioavailability 

摘      要：The objective of this work is to construct a nanosuspension drug delivery system of probucol,a BCS II drug,in order to improve its dissolution and oral bioavailability.The wet milling procedure using planetary beads-milling equipment was utilized to grind the raw probucol to ultrafine nanoparticle/nanocrystal aqueous suspension that was further solidified by freeze-drying process.Cellulose derivatives of different substitution groups and molecular weights,including HPMC,HPC,and MC,were evaluated as the primary stabilizer of probucol nanosuspension.Ternary stabilizers system composed of a primary stabilizer(cellulose derivative,i.e.HPC),a nonionic surfactant(Pluronic R F68),and an anionic surfactant(SDS)was employed to obtain probucol nanosuspension of finer particle size and enhanced dissolution in aqueous media.The probucol nanosuspension with good physical stability showed no obvious change of particle size even after storing over 7 d at 4°C or 25°C.The solidified probucol nanosuspension with trehalose as the cryoprotectant showed the highest dissolution rate(60%at 2 h)compared to other cryoprotectant.The in vivo pharmacokinetic evaluation indicated about 15-folds higher AUC value of the probucol nanosuspension compared to that of coarse probucol suspension after oral administration to rats.The probucol nanosuspension prepared by wet-milling and ternary stabilizers system may find wide applications for improving the dissolution and oral absorption of water-insoluble drugs.