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姜黄素的抗溶剂沉淀法纳米化:工艺开发、表征、冷冻干燥及稳定性研究

Nanonization of curcumin by antisolvent precipitation: process development, characterization, freeze drying and stability performance.

作者信息

Yadav Deepak, Kumar Neeraj

机构信息

Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, Punjab 160067, India.

Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, Punjab 160067, India.

出版信息

Int J Pharm. 2014 Dec 30;477(1-2):564-77. doi: 10.1016/j.ijpharm.2014.10.070. Epub 2014 Nov 3.

DOI:10.1016/j.ijpharm.2014.10.070
PMID:25445971
Abstract

The present work aims to investigate applicability of antisolvent precipitation method for preparation of nanosized curcumin and to control their characteristics by determining the influence of process and solvents on solid-state properties of curcumin nanoparticles. Effects of different experimental parameters on particle size were investigated using dynamic light scattering. Particle morphology was studied using SEM. Drug content in stabilized nanoparticles was determined using HPLC. Residual moisture content after lyophilisation was determined using Karl Fischer method and solid state properties were investigated using DSC, TGA, FTIR and powder-XRD. The resulting product showed a high drug load and contained the drug in amorphous form. The particle diameters of prepared curcumin nanoparticles were found in the range of 100-200 nm. In vitro drug release studies indicated a sustained release profile of curcumin from the nanoparticles. Antisolvent precipitation produced amorphous curcumin nanoparticles whose size and morphology could be controlled using gelatine as stabilizer. Lyophilized curcumin nanoparticles with d-sorbitol as lyoprotectant possessed good redispersibility and showed up to 4 times faster in vitro curcumin release rate than that of unprocessed curcumin. Stability tests (at 2-8°C and ambient conditions) indicated that the product was stable for up to 6 months of storage.

摘要

本研究旨在探讨抗溶剂沉淀法制备纳米姜黄素的适用性,并通过确定工艺和溶剂对姜黄素纳米颗粒固态性质的影响来控制其特性。使用动态光散射研究不同实验参数对粒径的影响。使用扫描电子显微镜研究颗粒形态。使用高效液相色谱法测定稳定化纳米颗粒中的药物含量。使用卡尔费休法测定冻干后的残留水分含量,并使用差示扫描量热法、热重分析法、傅里叶变换红外光谱法和粉末X射线衍射法研究固态性质。所得产品显示出高载药量,且药物以无定形形式存在。制备的姜黄素纳米颗粒的粒径在100 - 200 nm范围内。体外药物释放研究表明姜黄素从纳米颗粒中呈现出缓释特征。抗溶剂沉淀法制备的无定形姜黄素纳米颗粒,其大小和形态可以使用明胶作为稳定剂进行控制。以d - 山梨醇作为冻干保护剂的冻干姜黄素纳米颗粒具有良好的再分散性,并且体外姜黄素释放速率比未处理的姜黄素快高达4倍。稳定性试验(在2 - 8°C和环境条件下)表明该产品在储存6个月内稳定。

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