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溶胶-凝胶法制备的用于控释的华法林-二氧化硅复合材料

Sol-gel Derived Warfarin - Silica Composites for Controlled Drug Release.

作者信息

Dolinina Ekaterina S, Parfenyuk Elena V

机构信息

Laboratory of Chemistry of Hybrid Nanomaterials and Supramolecular Systems, G.A. Krestov Institute of Solution Chemistry of Russian Academy of Sciences, 1 Akademicheskaya Str., Ivanono 153045. Russian Federation.

出版信息

Curr Drug Deliv. 2017;14(5):734-740. doi: 10.2174/1567201813666161021103714.

Abstract

BACKGROUND

Warfarin, commonly used anticoagulant in clinic, has serious shortcomings due to its unsatisfactory pharmacodynamics. One of the efficient ways for the improvement of pharmacological and consumer properties of drugs is the development of optimal drug delivery systems.

OBJECTIVE

The aim of this work is to synthesize novel warfarin - silica composites and to study in vitro the drug release kinetics to obtain the composites with controlled release.

METHODS

The composites of warfarin with unmodified (UMS) and mercaptopropyl modified silica (MPMS) were synthesized by sol-gel method. The composite formation was confirmed by FTIR spectra. The concentrations of warfarin released to media with pH 1.6, 6.8 and 7.4 were measured using UV spectroscopy. The drug release profiles from the solid composites were described by a series of kinetic models which includes zero order kinetics, first order kinetics, the modified Korsmeyer-Peppas model and Hixson-Crowell model.

RESULTS

The synthesized sol-gel composites have different kinetic behavior in the studied media. In contrast to the warfarin composite with unmodified silica, the drug release from the composite with mercaptopropyl modified silica follows zero order kinetics for 24 h irrespective to the release medium pH due to mixed mechanism (duffusion + degradation and/or disintegration of silica matrix).

CONCLUSION

The obtained results showed that warfarin - silica sol-gel composites have a potential application for the development of novel oral formulation of the drug with controlled delivery.

摘要

背景

华法林是临床上常用的抗凝剂,但由于其药效学不尽人意,存在严重缺点。改善药物药理和使用性能的有效方法之一是开发最佳药物递送系统。

目的

本研究旨在合成新型华法林-二氧化硅复合材料,并体外研究药物释放动力学,以获得具有控释性能的复合材料。

方法

采用溶胶-凝胶法合成了华法林与未改性二氧化硅(UMS)和巯基丙基改性二氧化硅(MPMS)的复合材料。通过傅里叶变换红外光谱(FTIR)证实了复合材料的形成。使用紫外光谱法测定释放到pH值为1.6、6.8和7.4介质中的华法林浓度。通过一系列动力学模型描述了固体复合材料的药物释放曲线,这些模型包括零级动力学、一级动力学、修正的Korsmeyer-Peppas模型和Hixson-Crowell模型。

结果

合成的溶胶-凝胶复合材料在研究介质中具有不同的动力学行为。与未改性二氧化硅的华法林复合材料相比,巯基丙基改性二氧化硅复合材料的药物释放由于混合机制(扩散+二氧化硅基质的降解和/或崩解)在24小时内遵循零级动力学,与释放介质的pH值无关。

结论

所得结果表明,华法林-二氧化硅溶胶-凝胶复合材料在开发新型口服控释制剂方面具有潜在应用价值。

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