CMAC, Technology and Innovation Centre, 99 George Street, Glasgow G1 1RD, UK.
GSK Ware R&D, Harris's Lane, Ware, Hertfordshire SG12 0GX, UK.
Int J Pharm. 2024 Jun 25;659:124232. doi: 10.1016/j.ijpharm.2024.124232. Epub 2024 May 16.
Continuous Direct Compaction (CDC) has emerged as a promising route towards producing solid dosage forms while reducing material, development time and energy consumption. Understanding the response of powder processing unit operations, especially blenders, is crucial. There is a substantial body of work around how lubrication via batch blender operation affects tablet critical quality attributes such as hardness and tensile strength. But, aside from being batch operations, the design of these blenders is such that they operate with low-shear, low-intensity mixing at Froude number values significantly below 0.4 (Froude number Fr being the dimensionless ratio of inertial to gravitational forces). The present work explores the performance of a mini-blender which has a fundamentally different mode of operation (static vessel with rotating blades around a mixing shaft as opposed to rotating vessel with no mixing shaft). This difference allows a substantially wider operating range in terms of speed and shear (and Fr values). The present work evaluates how its performance compares to other blenders studied in the literature. Tablet compaction data from blends produced at various intensities and regimes of mixing in the mini-blender follow a common trajectory. Model equations from literature are suitably modified by inclusion of the Froude number Fr, but only for situations where the Froude number was sufficiently high (1 < Fr). The results suggest that although a similar lubrication extent plateau is eventually reached it is the intensity of mixing (i.e. captured using the Froude number as a surrogate) which is important for the lubrication dynamics in the mini-blender, next to the number of revolutions. The degree of fill or headspace, on the other hand, is only crucial to the performance of common batch blenders. Testing using alternative formulations shows the same common trend across mixing intensities, suggesting the validity of the approach to capture lubrication dynamics for this system.
连续直接压缩（CDC）已成为生产固体剂型的一种很有前途的方法，同时可以减少材料、开发时间和能源消耗。了解粉末加工单元操作的反应，特别是混合器的反应，至关重要。有大量的工作研究了通过批处理混合器操作进行润滑如何影响片剂的关键质量属性，如硬度和拉伸强度。但是，除了是批处理操作之外，这些混合器的设计使得它们以低剪切、低强度混合的方式运行，弗劳德数（Fr）值显著低于 0.4（Fr 是惯性力与重力的无量纲比）。本工作探索了一种微型混合器的性能，该混合器具有根本不同的操作模式（与没有混合轴的旋转容器相比，具有旋转轴和旋转叶片的静态容器）。这种差异允许在速度和剪切（以及 Fr 值）方面有更大的操作范围。本工作评估了其性能与文献中研究的其他混合器的比较。在微型混合器中以各种强度和混合阶段生产的混合物的片剂压缩数据遵循共同的轨迹。通过包括弗劳德数 Fr 来适当修改文献中的模型方程，但仅适用于 Fr 值足够高（1 < Fr）的情况。结果表明，尽管最终达到了相似的润滑程度平台，但对于微型混合器中的润滑动力学来说，重要的是混合强度（即使用 Fr 作为替代来捕获），其次是旋转次数。另一方面，填充程度或头空间仅对常见批处理混合器的性能至关重要。使用替代配方进行的测试表明，在混合强度方面呈现出相同的共同趋势，这表明了这种方法对于捕获该系统的润滑动力学的有效性。
