Leung Lap Yin, Mao Chen, Srivastava Ishan, Du Ping, Yang Chia-Yi
Small Molecule Pharmaceutical Sciences, Genentech, Inc., South San Francisco, California 94080.
Small Molecule Pharmaceutical Sciences, Genentech, Inc., South San Francisco, California 94080.
J Pharm Sci. 2017 Jul;106(7):1865-1873. doi: 10.1016/j.xphs.2017.04.012. Epub 2017 Apr 14.
The purpose of this study was to demonstrate that the flow function (FFc) of pharmaceutical powders, as measured by rotational shear cell, is predominantly governed by cohesion but not friction coefficients. Driven by an earlier report showing an inverse correlation between FFc and the cohesion divided by the corresponding pre-consolidation stress (Wang et al. 2016. Powder Tech. 294:105-112), we performed analysis on a large data set containing 1130 measurements from a ring shear tester and identified a near-perfect inverse correlation between the FFc and cohesion. Conversely, no correlation was found between FFc and friction angles. We also conducted theoretical analysis and estimated such correlations based on Mohr-Coulomb failure model. We discovered that the correlation between FFc and cohesion can sustain as long as the angle of internal friction at incipient flow is not significantly larger than the angle of internal friction at steady-state flow, a condition covering almost all pharmaceutical powders. The outcome of this study bears significance in pharmaceutical development. Because the cohesion value is strongly influenced by the interparticle cohesive forces, this study effectively shows that it is more efficient to improve the pharmaceutical powder flow by lowering the interparticle cohesive forces than by lowering the interparticle frictions.
本研究的目的是证明通过旋转剪切池测量的药用粉末的流动函数(FFc)主要受内聚力而非摩擦系数的控制。受早期一份报告的推动,该报告显示FFc与内聚力除以相应的预固结应力之间存在负相关(Wang等人,2016年。《粉末技术》294:105 - 112),我们对一个包含来自环剪测试仪的1130次测量的大型数据集进行了分析,并确定了FFc与内聚力之间近乎完美的负相关。相反,未发现FFc与摩擦角之间存在相关性。我们还进行了理论分析,并基于莫尔 - 库仑破坏模型估计了此类相关性。我们发现,只要初始流动时的内摩擦角不显著大于稳态流动时的内摩擦角,FFc与内聚力之间的相关性就可以维持,这种情况涵盖了几乎所有的药用粉末。本研究的结果在药物研发中具有重要意义。由于内聚力值受颗粒间内聚合力的强烈影响,本研究有效地表明,通过降低颗粒间内聚合力来改善药用粉末的流动性比通过降低颗粒间摩擦力更有效。