Fang Longwei, Yin Xianzhen, Wu Li, He Yaping, He Yuanzhi, Qin Wei, Meng Fanyue, York Peter, Xu Xu, Zhang Jiwen
School of Chemical and Environmental Engineering, Shanghai Institute of Technology, Shanghai 201418, China; Center for Drug Delivery System, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Center for Drug Delivery System, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; Institute of Pharmaceutical Innovation, University of Bradford, Bradford, West Yorkshire BD7 1DP, United Kingdom.
Int J Pharm. 2017 Oct 15;531(2):658-667. doi: 10.1016/j.ijpharm.2017.05.019. Epub 2017 May 10.
Microcrystalline cellulose (MCC) is one of the most important excipients due to its outstanding binding and tableting properties. Owing to the absence of high resolution characterization techniques at the single particle scale, 3D (three dimension) microstructure of MCC and its effects on formulation performance remain unexamined. The aim of this work was to establish a methodology for single particles of MCC type 102 based on synchrotron radiation X-ray micro computed tomography (SR-μCT), principal component analysis (PCA) and partial least square discriminant analysis (PLSDA). Scanning electron microscopy, SR-μCT, powders properties together with tensile strength (TS), disintegration time (DT), Kawakita plots and force/displacement profiles of tablets were measured. PCA-PLSDA was applied to evaluate the structural classification of MCC particles on the basis of 2D and 3D SR-μCT derived images. The studied MCCs were found to differ in the TS, DT, Kawakita plot and force/displacement, while box ratio and Feret ratio had major influence on the principal components, but the angle of repose, bulk and tapped density did not exhibit significantly. These findings verified that different samples of MCCs from alternative suppliers have morphological diversity when assessed at the individual particle level, which could result into variation in powder properties and tableting performance.
微晶纤维素(MCC)因其出色的黏合和压片性能而成为最重要的辅料之一。由于缺乏单颗粒尺度的高分辨率表征技术,MCC的三维微观结构及其对制剂性能的影响仍未得到研究。本研究的目的是基于同步辐射X射线显微计算机断层扫描(SR-μCT)、主成分分析(PCA)和偏最小二乘判别分析(PLSDA),建立一种针对102型MCC单颗粒的方法。测量了扫描电子显微镜、SR-μCT、粉体性质以及片剂的抗张强度(TS)、崩解时间(DT)、河合图和力/位移曲线。应用PCA-PLSDA基于二维和三维SR-μCT衍生图像评估MCC颗粒的结构分类。研究发现,所研究的MCC在TS、DT、河合图和力/位移方面存在差异,而盒形比和费雷特比(Feret ratio)对主成分有主要影响,但休止角、堆密度和振实密度没有显著表现。这些发现证实,当在单个颗粒水平进行评估时,来自不同供应商的不同MCC样品具有形态多样性,这可能导致粉体性质和压片性能的差异。