Original articles
Yinqian Yang, Yongjiu Lv, Chengying Shen, Tingting Shi, Haisheng He, Jianping Qi, Xiaochun Dong, Weili Zhao, Yi Lu, Wei Wu. In vivo dissolution of poorly water-soluble drugs: Proof of concept based on fluorescence bioimaging[J]. Acta Pharmaceutica Sinica B, 2021, 11(4): 1056-1068

In vivo dissolution of poorly water-soluble drugs: Proof of concept based on fluorescence bioimaging
Yinqian Yanga, Yongjiu Lva, Chengying Shena, Tingting Shia, Haisheng Hea, Jianping Qia, Xiaochun Donga, Weili Zhaoa, Yi Lua, Wei Wua,b
a Key Laboratory of Smart Drug Delivery of MOE, School of Pharmacy, Fudan University, Shanghai 201203, China;
b Center for Medical Research and Innovation, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai 201399, China
Abstract:
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 profiles 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 fenofibrate (FNB) was investigated by fluorescence bioimaging. FNB crystals were first labeled by near-infrared fluorophores 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 fluorescence and crystal concentration justified reliable quantification of FNB crystals. In vitro dissolution was first measured following pharmacopoeia monograph protocols with well-documented IVIVC. The synchronicity between fluorescence and in vitro dissolution of FNB supported using fluorescence 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 Fa obtained from pharmacokinetic data.
Key words:    In vivo dissolution    Fenofibrate    Fluorescence    Aggregation-caused quenching    Bioimaging    IVIVC   
Received: 2020-04-18     Revised: 2020-06-16
DOI: 10.1016/j.apsb.2020.08.002
Funds: This work was supported by the National Natural Science Foundation of China (Nos. 81973247, 81872815, 81872826 and 81690263) and Science and Technology Commission of Shanghai Municipality (19XD1400300, China). We are grateful for Prof. Dr. Yu-Kyoung Oh of Seoul National University Nano Biodrug Delivery Lab for the illuminating comments she provided.
Corresponding author: Wei Wu, wuwei@shmu.edu.cn     Email:wuwei@shmu.edu.cn
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Yinqian Yang
Yongjiu Lv
Chengying Shen
Tingting Shi
Haisheng He
Jianping Qi
Xiaochun Dong
Weili Zhao
Yi Lu
Wei Wu

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