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

Autor: Tong M; Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, 100 Shizi Road, Nanjing, Jiangsu 210028, China., Wu X; Pharmacy, Nanjing Drum Tower Hospital, The affiliated hospital of Nanjing University Medical School, Nanjing 210008, China., Zhang S; Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, 100 Shizi Road, Nanjing, Jiangsu 210028, China., Hua D; Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, 100 Shizi Road, Nanjing, Jiangsu 210028, China., Li S; Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, 100 Shizi Road, Nanjing, Jiangsu 210028, China., Yu X; Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, 100 Shizi Road, Nanjing, Jiangsu 210028, China., Wang J; Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, 100 Shizi Road, Nanjing, Jiangsu 210028, China. Electronic address: wangjing3968@126.com., Zhang Z; Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, 100 Shizi Road, Nanjing, Jiangsu 210028, China. Electronic address: david23932@163.com.
Jazyk: angličtina
Zdroj: European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences [Eur J Pharm Sci] 2022 Jan 01; Vol. 168, pp. 106071. Date of Electronic Publication: 2021 Nov 11.
DOI: 10.1016/j.ejps.2021.106071
Abstrakt: 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.
(Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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