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用于提高姜黄素口服生物利用度的基于脂质/粘土的固体分散体制剂

Lipid/Clay-Based Solid Dispersion Formulation for Improving the Oral Bioavailability of Curcumin.

作者信息

Song Jae Geun, Noh Hye-Mi, Lee Sang Hoon, Han Hyo-Kyung

机构信息

BK21 FOUR Team and Integrated Research Institute for Drug Development, College of Pharmacy, Dongguk University-Seoul, Dongguk-ro-32, Ilsan-Donggu, Goyang 10326, Korea.

出版信息

Pharmaceutics. 2022 Oct 24;14(11):2269. doi: 10.3390/pharmaceutics14112269.

Abstract

This study was conducted to develop a lipid/clay-based solid dispersion (LSD) formulation to enhance the dissolution and oral bioavailability of poorly soluble curcumin. Krill oil and aminoclay were used as a lipid and a stabilizer, respectively, and LSD formulations of curcumin were prepared by an antisolvent precipitation method combined with freeze-drying process. Based on the dissolution profiles, the optimal composition of LSD was determined at the weight ratio of curcumin: krill oil: aminoclay of 1:5:5 in the presence of 0.5% of D-α-tocopherol polyethylene glycol succinate. The structural and morphological characteristics of the LSD formulation were determined using X-ray powder diffraction, differential scanning calorimetry, and scanning electron microscopy. Crystalline curcumin was changed to an amorphous form in the LSD formulation. At the pH of acidic to neutral, the LSD formulation showed almost complete drug dissolution (>90%) within 1 h, while pure curcumin exhibited minimal dissolution of less than 10%. Furthermore, the LSD formulation had significantly improved oral absorption of curcumin in rats, where Cmax and AUC of curcumin were 13- and 23-fold higher for the LSD formulation than for the pure drug. Taken together, these findings suggest that the krill oil-based solid dispersion formulation of curcumin effectively improves the dissolution and oral bioavailability of curcumin.

摘要

本研究旨在开发一种基于脂质/粘土的固体分散体(LSD)制剂,以提高难溶性姜黄素的溶出度和口服生物利用度。分别使用磷虾油和氨基粘土作为脂质和稳定剂,并通过反溶剂沉淀法结合冷冻干燥工艺制备姜黄素的LSD制剂。基于溶出曲线,在0.5%的聚乙二醇琥珀酸维生素E存在下,确定LSD的最佳组成是姜黄素:磷虾油:氨基粘土的重量比为1:5:5。使用X射线粉末衍射、差示扫描量热法和扫描电子显微镜确定LSD制剂的结构和形态特征。在LSD制剂中,结晶姜黄素转变为无定形形式。在酸性至中性pH值下,LSD制剂在1小时内显示几乎完全的药物溶出(>90%),而纯姜黄素的溶出度极小,低于10%。此外,LSD制剂显著提高了姜黄素在大鼠体内的口服吸收,其中姜黄素的Cmax和AUC,LSD制剂比纯药物分别高13倍和23倍。综上所述,这些发现表明基于磷虾油的姜黄素固体分散体制剂有效地提高了姜黄素的溶出度和口服生物利用度。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6823/9697399/455f8d341ec7/pharmaceutics-14-02269-g001.jpg

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