Application of TPGS as an efflux inhibitor and a plasticizer in baicalein solid dispersion

The oral bioavailability and efficacy of baicalein is dramatically limited by its low solubility and effect of efflux. In our study, we chose PVP-VA64 as a carrier and TPGS as a plasticizer and efflux inhibitor to prepare a solid dispersion of baicalein using hot-melt extrusion technology to improve its solubility and bioavailability. The hot-melt process and formulation were optimized, and a BAC-PVP VA64-TPGS solid dispersion (BPT-SD) was prepared. BAC exists in an amorphous or molecular state in BPT-SD. BPT-SD comprised irregular lumps and small particles without BAC or carrier characteristics.

The dissolution efficiency of BPT-SD improved under sink conditions. FTIR showed a strong hydrogen bond between BAC and PVP-VA64 in BPT-SD. BPT-SD maintained good physical stability for 6 months. The apparent permeability coefficient of BAC in the Caco-2 cell model confirmed that BPT-SD had higher gastrointestinal membrane permeability. A rat pharmacokinetic study showed that BPT-SD had higher C_max and AUC_0-24h, shorter T_max, and 2.88-fold higher bioavailability than BAC. A behavioral experiment in chronic unpredictable mild stress (CUMS) mice confirmed the antidepressant efficacy of BAC. BPT-SD reversed depression-like behavior in CUMS mice and improved BAC bioavailability. BAC preparation into a solid dispersion significantly enhanced dissolution performance and bioavailability.

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Meng Tong, Xiaoyan Wu, Shuya Zhang, Di Hua, Shukun Li, Xiangyu Yu, Jing Wang, Zhenhai Zhang,
Application of TPGS as an efflux inhibitor and a plasticizer in baicalein solid dispersion,
European Journal of Pharmaceutical Sciences, Volume 168, 2022, 106071, ISSN 0928-0987,
https://doi.org/10.1016/j.ejps.2021.106071.

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