Research Center Pharmaceutical Engineering GmbH, Graz, Austria.
Research Center Pharmaceutical Engineering GmbH, Graz, Austria; Institute for Process and Particle Engineering, Graz University of Technology, Graz, Austria.
J Pharm Sci. 2019 Jan;108(1):538-550. doi: 10.1016/j.xphs.2018.10.016. Epub 2018 Oct 16.
Large-scale fluid bed coating operations using Wurster coaters are common in the pharmaceutical industry. Experimental measurements of the coating thickness are usually analyzed for just few particles. To better predict the coating uniformity of the entire batch, computational techniques can be applied for process understanding of the key process parameters that influence the quality attributes. Recent advances in computational hardware, such as graphics processing unit, have enabled simulations of large industrial-scale systems. In this work, we perform coupled computational fluid dynamics-discrete element method simulations of a large-scale coater that model the actual particle sizes. The influence of process parameters, inlet air flow rate, atomizing air flow rate, bead size distribution, and Wurster gap height is studied. The focus of this study is to characterize the flow inside the coater; eventually, this information will be used to predict the coating uniformity of the beads. We report the residence time distribution of the beads inside the Wurster column, that is, the active coating zone, which serves as a proxy for the amount of coating received by the beads per pass. The residence time provides qualitative and quantitative measurements of the particle-coating uniformity. We find that inlet air flow rate has the largest impact on the flow behavior and, hence, the coating uniformity.
在制药行业中，使用 Wurster 包衣机进行大规模流化床包衣操作是很常见的。通常只对少数几个颗粒进行涂层厚度的实验测量。为了更好地预测整个批次的涂层均匀性，可以应用计算技术来了解影响质量属性的关键工艺参数的过程。最近，计算硬件的进步，如图形处理单元，已经使得对大型工业规模系统的模拟成为可能。在这项工作中，我们对大型包衣机进行了耦合计算流体动力学-离散元方法的模拟，模拟实际的颗粒大小。研究了工艺参数、进气流量、雾化空气流量、珠粒尺寸分布和 Wurster 间隙高度的影响。这项研究的重点是描述包衣机内的流动；最终，这些信息将用于预测珠粒的涂层均匀性。我们报告了 Wurster 柱内珠粒的停留时间分布，即活性涂层区，它是每个通过时珠粒所接受的涂层量的代理。停留时间提供了颗粒涂层均匀性的定性和定量测量。我们发现进气流量对流动行为，从而对涂层均匀性的影响最大。
