文献类型：期刊文献

英文题名：Development of a gliclazide ionic liquid and its mesoporous silica particles: an effective formulation strategy to improve oral absorption properties

作者：Zhou, Bijian[1];Teng, Dan[2];Li, Jinghui[1];Zhang, Yanhong[1];Qi, Minghui[1];Hong, Minghuang[1];Ren, Guo-Bin[1,3]

机构：[1]East China Univ Sci & Technol, Engn Res Ctr Pharmaceut Proc Chem, Lab Pharmaceut Crystal Engn & Technol, Minist Educ, 130 Meilong Rd, Shanghai 200237, Peoples R China;[2]East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, Shanghai 200237, Peoples R China;[3]East China Univ Sci & Technol, Shanghai Key Lab New Drug Design, State Key Lab Bioreactor Engn, 130 Meilong Rd, Shanghai 200237, Peoples R China

年份：2021

卷号：12

期号：2

起止页码：1062

外文期刊名：RSC ADVANCES

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000739550900001)】；

基金：The authors acknowledge the financial support received from Natural Science Foundation of Shanghai (No. 20ZR1413600) and the National Natural Science Foundation of China (No. 21576080), for their support and encouragement in carrying out his college work.

语种：英文

摘要：Ionic liquid (IL) technology provides a useful platform to enhance the oral absorption of therapeutic agents. In the present work, gliclazide (GLI), a second-generation sulfonylurea drug was transformed into an IL with tetrabutylphosphonium. The physicochemical properties of this IL were systematically characterized by DSC, TGA, FT-IR, NMR, and HPLC. For the further preparation development, a solution stability test was conducted. GLI-based IL could improve the solution stability in a neutral environment. To assess oral potential, the solubility characteristics including equilibrium solubility, 24 h kinetic saturation solubilities and supersaturation profiles were first explored. Significant enhancement of solubilities, supersaturation ratio and duration of supersaturation was found for the synthesized IL. Computational methodology was utilized to better understand the improved solubility results. From the simulated results, [TBP][GLI] showed a longer time period when the distance between cation and anion was far above the baseline and a higher deviation degree, indicating less stable ion pairs of [TBP][GLI] in an aqueous environment and it being easy for the cation and anion to tear apart and form interactions with water molecules. The prepared [TBP][GLI] exhibited intestinal transportation ability and safety as evidenced by the in vitro gastrointestinal tract artificial membrane permeability assays (GIT-PAMPA) and cytotoxicity experiments with Caco-2 cells. A mesoporous carrier, AEROPERL (R) 300 Pharma, was chosen to load the IL and then encapsuled into enteric capsules. The prepared oral capsules containing GLI-based IL loaded mesoporous silica particles released fast and could realize 100% release within 60 min.