Small Molecule Pharmaceutical Sciences, Genentech, Inc., South San Francisco, California 94080.
Drug Product Process R&D, F. Hoffmann-La Roche Ltd., 4070 Basel, Switzerland.
J Pharm Sci. 2021 Mar;110(3):1172-1181. doi: 10.1016/j.xphs.2020.10.007. Epub 2020 Oct 10.
The purpose of this study is to assess the prevalence of funnel flow pattern for common pharmaceutical powder blends, upon discharging from modern intermediate bulk containers (IBCs) in drug product manufacturing. The estimation was built upon Jenike's original radial stress field theory. It was modified to account for the stress-dependence of wall friction angle commonly observed in pharmaceutical powders. A total of 260 flow pattern estimations, based on 20 real-life IBCs and 13 investigational powder blends, were made. The estimated results showed that the mass flow pattern is present in less than 5% of all cases. Funnel flow pattern is clearly prevalent among pharmaceutical powder blends. The prevalence of funnel flow stems from several factors: 1) relatively shallow hopper section shared by all IBCs, 2) the common transition-type geometry, leading to even shallower hopper inclination at the edge of the hopper section, and 3) relatively high wall friction angles resulting from low wall normal stresses. This conclusion was verified through at-scale experiments, by discharging multiple pharmaceutical powder blends from a representative IBC. In general, our study suggests that, unless the powder wall friction can be substantially reduced, pharmaceutical powders are likely to discharge under funnel flow from modern IBCs.
本研究旨在评估在药物产品制造过程中,从现代中型散装容器(IBC)中排出时常见药用粉末混合物的漏斗流模式的流行程度。该评估是基于 Jenike 的原始径向应力场理论建立的。它经过修改,以考虑到在制药粉末中通常观察到的壁摩擦角对应力的依赖性。总共基于 20 个实际的 IBC 和 13 个研究性粉末混合物进行了 260 次流动模式估计。估计结果表明,质量流动模式在所有情况下不到 5%。漏斗流模式在药用粉末混合物中明显流行。漏斗流的流行源于几个因素:1)所有 IBC 共享的相对较浅的料斗部分,2)常见的过渡型几何形状,导致料斗部分边缘的料斗倾斜度甚至更浅,以及 3)相对较高的壁摩擦角,这是由于壁正应力较低。通过从具有代表性的 IBC 中排出多种药用粉末混合物的比例实验验证了这一结论。总的来说,我们的研究表明,除非可以大幅降低粉末壁摩擦,否则药用粉末很可能会从现代 IBC 中以漏斗流的形式排出。