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胶体二氧化硅改善药用辅料流变性的作用机制。

On the mechanism of colloidal silica action to improve flow properties of pharmaceutical excipients.

机构信息

Department of Organic Technology, Faculty of Chemical Technology, University of Chemistry and Technology, Prague, Technická 5, Prague 6 166 28, Czech Republic.

Department of Multiphase Reactors, Institute of Chemical Process Fundamentals of the ASCR, Rozvojová 2/135, Prague 6 165 02, Czech Republic.

出版信息

Int J Pharm. 2019 Feb 10;556:383-394. doi: 10.1016/j.ijpharm.2018.11.066. Epub 2018 Dec 6.

Abstract

The mechanism of colloidal silica action to improve flow properties of pharmaceutical powders is known to be based on inter-particle force disruption by silica particles adhered to the particle surface. In the present article, the kinetic aspects of this action are investigated, focusing on non-spherical particles of different size. Blends comprising microcrystalline cellulose or calcium hydrogen phosphate dihydrate and colloidal silica were examined using powder rheometer. The blends were formulated to represent effects of particle size, surface texture, colloidal silica loading, and mixing time. Pre-conditioning, shear testing, compressibility, and flow energy measurements were used to monitor flow properties. Components and blends were analyzed using particle size analysis and scanning electron microscopy (SEM), using energy dispersive spectroscopy (EDS) and back-scattered electron (BSE) detection to determine surface particle arrangement. All studied parameters were found to have substantial effects on flow properties of powder blends. Those effects were explained by identifying key steps of colloidal silica action, which were found to proceed at substantially different rates, causing the flow properties change over time being dependent on the blend formulation and the component properties.

摘要

胶态二氧化硅改善药物粉末流动性能的作用机制已知是基于附着在颗粒表面的二氧化硅颗粒破坏颗粒间的力。本文研究了这种作用的动力学方面,重点研究了不同大小的非球形颗粒。使用粉末流变仪研究了包含微晶纤维素或磷酸氢钙二水合物和胶态二氧化硅的混合物。这些混合物的配方旨在代表粒径、表面纹理、胶态二氧化硅负载和混合时间的影响。预处理、剪切测试、可压缩性和流动能量测量用于监测流动性能。使用粒度分析和扫描电子显微镜(SEM)对成分和混合物进行分析,使用能谱(EDS)和背散射电子(BSE)检测来确定表面颗粒排列。发现所有研究的参数对粉末混合物的流动性能都有很大的影响。通过确定胶态二氧化硅作用的关键步骤来解释这些影响,发现这些步骤的进行速度有很大的不同,导致流动性能随时间的变化取决于混合物的配方和成分的性质。

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