School of Chemistry and Chemical Engineering, University of Surrey, Guildford, Surrey GU2 7XH, UK.
School of Chemistry and Chemical Engineering, University of Surrey, Guildford, Surrey GU2 7XH, UK; School of Chemical Engineering, Newcastle University, Newcastle upon Tyne, NE1 7RU, UK.
Int J Pharm. 2024 Sep 5;662:124527. doi: 10.1016/j.ijpharm.2024.124527. Epub 2024 Jul 28.
Die filling is a crucial step in the pharmaceutical tablet manufacturing process. For industrial-scale production using rotary presses, suction filling is typically employed due to its significant efficiency advantages over gravity filling. Despite its widespread use, our understanding of the suction filling process remains limited. Specifically, there is insufficient comprehension of how filling performance is influenced by factors such as suction velocity, filling velocity, and the properties of the powder materials. Building on our previous research, this study aims to further investigate the effects of powder properties and process parameters (e.g., filling velocity, suction velocity, fill depth) on suction filling behaviour. A systematic experimental investigation was conducted using a model suction filling system, considering both cohesive and free-flowing pharmaceutical powders. The effect of fill depth on suction filling of these powders was examined at different filling and suction velocities. The results demonstrate that two distinctive flow regimes for suction filling can be identified: slow filling and fast filling. These regimes are delineated by a critical filling-to-suction velocity ratio. In the slow filling regime, the filling-to-suction velocity ratio is lower than the critical ratio, meaning that the filling phase is slower than the suction phase. Conversely, the fast filling regime occurs when the filling-to-suction velocity ratio exceeds the critical ratio, implying that the filling phase is faster than the suction phase. This study reveals, for the first time, that when the powder flow pattern during suction filling is dominated by plug flow, full die fill (i.e., the fill ratio equals unity) is achieved in the slow filling regime. However, in the fast filling regime, incomplete die fill is obtained. It is also found that when plug flow prevails during fast filling, the fill ratio has an inverse correlation with the filling-to-suction velocity ratio. This study further reveals that when the plug flow assumption is valid, the filling ratio at various fill-to-suction velocity ratios can be well predicted mathematically. Furthermore, it is also found that once the powder flow pattern differs from the ideal plug flow, which could be induced by the filling conditions and powder cohesion, the fill ratio can be overpredicted.
粉末的装填入模是制药片剂生产过程中的一个关键步骤。对于采用旋转压片机的工业规模生产，由于吸粉填装在效率上相对于重力填装具有显著优势，因此通常会选用吸粉填装。尽管它被广泛应用，但我们对吸粉填装过程的理解仍然有限。具体来说，对于装填性能如何受到吸粉速度、填装速度以及粉末材料特性等因素的影响，我们的理解还不够充分。基于我们之前的研究，本研究旨在进一步探讨粉末特性和工艺参数（如填装速度、吸粉速度、装粉深度）对吸粉填装行为的影响。本研究采用模型吸粉填装系统，对粘性和自由流动的药用粉末同时进行了系统的实验研究。考察了不同填装和吸粉速度下装粉深度对吸粉填装的影响。研究结果表明，吸粉填装可以分为两种截然不同的流动状态：慢速填装和快速填装。这两种状态由一个临界填装-吸粉速度比来区分。在慢速填装状态下，填装-吸粉速度比低于临界比值，这意味着填装阶段比吸粉阶段慢。相反，当填装-吸粉速度比超过临界比值时，就会出现快速填装状态，表明填装阶段比吸粉阶段快。本研究首次揭示，当吸粉填装过程中的粉末流动模式以塞流为主时，在慢速填装状态下可以实现完全的模具填满（即填装率等于 1）。然而，在快速填装状态下，无法实现完全的模具填满。研究还发现，当快速填装时塞流占主导地位时，填装率与填装-吸粉速度比呈反比关系。本研究进一步揭示，当塞流假设成立时，在各种填装-吸粉速度比下，填装率可以通过数学方法得到很好的预测。此外，还发现一旦粉末流动模式偏离理想的塞流，例如由于填装条件和粉末内聚性的影响，填装率可能会被高估。
