Abstract In recent years, novel developments in the continuous manufacturing of solid dosage forms using twin-screw wet granulation have grasped the attention of the pharmaceutical industry. In spite of this progress, there still exists a lack of fundamental knowledge on the physical processes occurring in the barrel of the twin-screw granulator. A major contributor to this knowledge gap has been the unavailability of measurements of granule properties (particle size, liquid content, porosity, etcetera) along the length of the barrel. Recently conducted tedious measurements at different barrel locations have been essential to build a hypothesis in terms of locally occurring mechanisms in twin-screw wet granulation. This paper proposes a novel kernel for modelling either the uni- or bimodal behaviour observed at different L/S ratios in the wetting zone, assuming pure aggregation only. Furthermore, a two stage (wetting and kneading zone) compartmental population balance model is constructed to successfully simulate granule sizes from preblend to the end of the granulator. This population balance model can simulate granule size distributions at a reasonable accuracy both in the case of single compartments as well as in the full two stage compartmental set-up. The proposed model in this paper is a first important step in knowledge build-up of twin-screw granulation and towards a general population balance model for twin-screw wet granulation.

中文翻译：

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关于双螺杆湿法制粒中颗粒尺寸分布的建模：新型隔室种群平衡模型的校准

摘要 近年来，利用双螺杆湿法制粒连续生产固体剂型的新进展引起了制药业的关注。尽管取得了这些进展，但仍然缺乏关于双螺杆造粒机机筒中发生的物理过程的基本知识。造成这种知识差距的一个主要因素是无法测量沿筒体长度的颗粒特性（粒度、液体含量、孔隙率等）。最近在不同桶位置进行的繁琐测量对于建立双螺杆湿法制粒局部发生机制的假设至关重要。本文提出了一种新的内核，用于对在润湿区中不同 L/S 比下观察到的单峰或双峰行为进行建模，假设仅假设纯聚集。此外，构建了一个两阶段（润湿和捏合区）隔室人口平衡模型，以成功模拟从预混到制粒机末端的颗粒大小。这种总体平衡模型可以以合理的精度模拟颗粒大小分布，无论是在单个隔间的情况下，还是在完整的两级隔间设置中。本文中提出的模型是建立双螺杆制粒知识和实现双螺杆湿法制粒的一般人口平衡模型的第一个重要步骤。构建了一个两阶段（润湿和捏合区）隔室人口平衡模型，以成功模拟从预混到制粒机末端的颗粒大小。这种总体平衡模型可以以合理的精度模拟颗粒大小分布，无论是在单个隔间的情况下，还是在完整的两级隔间设置中。本文中提出的模型是建立双螺杆制粒知识和实现双螺杆湿法制粒的一般人口平衡模型的第一个重要步骤。构建了一个两阶段（润湿和捏合区）隔室人口平衡模型，以成功模拟从预混到制粒机末端的颗粒大小。这种总体平衡模型可以以合理的精度模拟颗粒大小分布，无论是在单个隔间的情况下，还是在完整的两级隔间设置中。本文中提出的模型是建立双螺杆制粒知识和实现双螺杆湿法制粒的一般人口平衡模型的第一个重要步骤。