In vivo dissolution of poorly water-soluble drugs:Proof of concept based on fluorescence bioimaging  

作　　者：Yinqian Yang Yongjiu Lv Chengying Shen Tingting Shi Haisheng He Jianping Qi Xiaochun Dong Weili Zhao Yi Lu Wei Wu 

机构地区：[1]Key Laboratory of Smart Drug Delivery of MOE,School of Pharmacy,Fudan University,Shanghai 201203,China [2]Center for Medical Research and Innovation,Shanghai Pudong Hospital,Fudan University Pudong Medical Center,Shanghai 201399,China

出　　处：《Acta Pharmaceutica Sinica B》2021年第4期1056-1068,共13页药学学报（英文版）

基　　金：supported by the National Natural Science Foundation of China(Nos.81973247,81872815,81872826 and 81690263);Science and Technology Commission of Shanghai Municipality(19XD1400300,China)。

摘　　要：In vitro-in vivo correlation(IVIVC)of solid dosage forms should be established basically between in vitro and in vivo dissolution of active pharmaceutical ingredients.Nevertheless,in vivo dissolution profles have never been accurately portrayed.The current practice of IVIVC has to resort to in vivo absorption fractions(Fa).In this proof-of-concept study,in vivo dissolution of a model poorly watersoluble drug fenofbrate(FNB)was investigated by fuorescence bioimaging.FNB crystals were frst labeled by near-infrared fuorophores with aggregation-caused quenching properties.The dyes illuminated FNB crystals but quenched immediately and absolutely once been released into aqueous media,enabling accurate monitoring of residual drug crystals.The linearity established between fuorescence and crystal concentration justifed reliable quantifcation of FNB crystals.In vitro dissolution was frst measured following pharmacopoeia monograph protocols with well-documented IVIVC.The synchronicity between fuorescence and in vitro dissolution of FNB supported using fuorescence as a measure for determination of dissolution.In vitro dissolution correlated well with in vivo dissolution,acquired by either live or ex vivo imaging.The newly established IVIVC was further validated by correlating both in vitro and in vivo dissolution with Faobtained from pharmacokinetic data.

关 键 词：In vivo dissolution FENOFIBRATE FLUORESCENCE Aggregation-caused quenching BIOIMAGING IVIVC 

分 类 号：R944.2[医药卫生—药剂学]