In this work, we studied the influence of powder composition on packing density and other processing-relevant properties of binary mixtures, including powder flowability. Binary mixtures of pharmaceutical powders with different particle size ratios, α and varying fractions of large and small particles were analyzed systematically. Mixtures of three excipients and one API with different composition (2, 5, 10, 30, 50, 70, 90, 95 and 98 wt%) were prepared in a Turbula mixer. Powders with different properties and particle size distribution were chosen, in order to obtain three binary mixtures with different size ratios. Then, macroscopic powder properties including bulk (poured) and tapped density (BD and TD) were measured. A powder rheometer was used to measure the flow function coefficient (ffc), cohesion, compressibility and permeability of the binary mixtures. We considered experimentally three classes of binary mixtures, which are characterized by two critical ratios of particle diameter: the critical size ratio of entrance (α_c) and the critical size ratio of replacement (α_r), where α_c = 0.154 and α_r = 0.741. Below the critical size ratio of entrance (α_c), the particle asymmetry (ratio between large and small particle diameters) is high and small particles can fill the voids between larger ones. Between α_c and the critical size ratio of replacement (α_r), the smaller particles are too large to fit in the voids between larger particles (packing structure changes). Above α_r, the particles are more or less symmetric in size and overall packing structure does not change by mixing the particles. Our experiments show that there is a non-linear and non-monotonic dependence of all relevant properties on composition for powder mixtures that have an α < α_r. This non-linear behavior is even more significant for strongly asymmetric binary mixtures with α < α_c. We argue that this behavior is related to the composition dependence of random packing of particulate systems. Our results have relevance to pharmaceutical particle processing operations where constant powder mixture properties are needed to ensure quality standards are met; such operations include capsule or die filling during tableting, and the continuous feeding of powders via screw feeders. Our results suggest that for pharmaceutical particle processing operations, where constant powder mixture properties are a prerequisite for process robustness, the size ratio of API and excipient particles, α should not be smaller than α_r = 0.741.

在这项工作中，我们研究了粉末组成对填充密度和二元混合物其他与加工相关的特性（包括粉末流动性）的影响。系统分析了具有不同粒径比，α和不同大小颗粒的药物粉末的二元混合物。在Turbula混合器中制备了三种赋形剂和一种具有不同组成（2、5、10、30、50、70、90、95和98 wt％）的API的混合物。选择具有不同性质和粒度分布的粉末，以获得三种具有不同尺寸比的二元混合物。然后，测量包括散装（浇注）和堆积密度（BD和TD）在内的宏观粉末性能。粉末流变仪用于测量流量函数系数（ffc），内聚力，二元混合物的可压缩性和渗透性。我们从实验上考虑了三类二元混合物，它们的特征在于两个关键的粒径比：入口的临界尺寸比（α_Ç）和替换（α的临界尺寸比_[R ），其中，α _{c ^}  = 0.154和α _{- [R}  = 0.741。下面入口的临界尺寸比（α _Ç），该颗粒的不对称性（大，小颗粒直径之比）为高和小颗粒可填充较大的之间的空隙。α之间_Ç和更换（α的临界尺寸比_[R ），较小的颗粒太大，以适应较大的颗粒（包装结构的变化）之间的空隙。高于_αr，颗粒的大小或多或少是对称的，并且通过混合颗粒不会改变整体堆积结构。我们的实验表明，对于具有<< _αr的粉末混合物，所有相关特性对组分的组成都具有非线性和非单调依赖性。此非线性行为是强不对称二元混合物与α<α更显著_Ç。我们认为这种行为与颗粒系统的随机堆积的成分依赖性有关。我们的结果与需要恒定粉末混合物特性以确保满足质量标准的药物颗粒处理操作有关；这样的操作包括在压片过程中填充胶囊或冲模，以及通过螺旋进料器连续进料粉末。我们的结果表明，对于药物颗粒加工操作而言，恒定的粉末混合物特性是过程鲁棒性的前提，API和赋形剂颗粒的尺寸比应不小于_αr  = 0.741。