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-VA 64 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由不规则的肿块和小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 Cmaxand AUC0-24h, shorter Tmax, 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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Materials:BAC (purity > 95%) was purchased from Aladdin Bio-Chem Technology Co., Ltd. (Shanghai, China).PVP VA64andTPGSwere kindly supplied by Chineway Pharmaceutical Tech. Co. Ltd. (Shanghai, China). Fluoxetine hydrochloride (FLU) (positive control drug) was obtained from Changzhou Siyao Pharmaceuticals Co., Ltd. (Changzhou, China). All other chemicals were of analytical grade.

Article information: 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, 2021.

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