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] Engineering Research Centre of Pharmaceutical Process Chemistry, Ministry of Education, Laboratory of Pharmaceutical Crystal Engineering and Technology, East China University of Science and Technology, No. 130 Meilong Road, Shanghai, 200237, China; [2] Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China; [3] State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of New Drug Design, East China University of Science and Technology, No. 130 Meilong Road, Shanghai, 200237, China

年份：2022

卷号：12

期号：2

起止页码：1062

外文期刊名：RSC Advances

收录：EI(收录号：20220311488160)

语种：英文

外文关键词：Silica - Targeted drug delivery - Molecules - Controlled drug delivery - Encapsulation - Solubility - Positive ions - Mesoporous materials - Physicochemical properties - Supersaturation

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? 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. ? The Royal Society of Chemistry.