Laboratory of Pharmaceutical Technology, Ghent University, Ghent, Belgium.
Regional Centre of Advanced Technologies and Materials, Palacky University, Olomouc, Czech Republic.
Int J Pharm. 2018 Sep 5;548(1):54-61. doi: 10.1016/j.ijpharm.2018.06.047. Epub 2018 Jun 22.
Despite the high quantities of tablets produced daily, many tableting processes are still operated at sub-optimal settings and hence lack the necessary flexibility to mitigate for possible process deviations. However, to ensure this flexibility on tableting throughput it is important to select the most robust feed frame design and settings regarding die-filling. In this research study, four paddle designs for a two-compartment forced feeder (equipped with a metering and a feeding paddle wheel) were evaluated at a wide range of process-settings (i.e. tableting speed, paddle speed, overfill level) and feed frame features (i.e. deaeration) for their impact on the die-filling step of a poorly flowing model formulation (i.e. MCC 101) using a quality-by-design approach. No benefit on die-filling was observed when using higher speeds of the metering paddle wheel compared to the feeding paddle wheel, and no convincing arguments were obtained to use the feed frame deaeration opening. Some combinations of paddle design and process-settings significantly increased the risk for inconsistent die-filling (i.e. high tablet weight variability) which can therefore limit the efficiency of the tableting process. The approach used in this study enabled to compare the paddle designs for their die-filling performance in function of varying tableting speeds, eventually resulting in the selection of a feed frame design that is most robust and therefore will provide a uniform die-filling over a wide range of throughputs. Selection of the most robust parameters is an important prerequisite for the ability of using the rotary tablet press as an agile unit-operation.
尽管每天生产的片剂数量很大,但许多压片工艺仍在次优的条件下运行,因此缺乏必要的灵活性来缓解可能的工艺偏差。然而,为了确保压片产量的这种灵活性,选择最稳健的送料器设计和关于冲模填充的设置非常重要。在这项研究中,使用质量源于设计的方法,在广泛的工艺条件(例如压片速度、桨叶速度、过量填充水平)和送料器特征(例如脱气)下,评估了用于两个隔室强制送料器(配备计量桨叶和送料桨叶)的四种桨叶设计,对一种流动性差的模型配方(即 MCC101)的冲模填充步骤的影响。与送料桨叶相比,计量桨叶的速度较高时,对冲模填充没有好处,并且没有令人信服的理由使用送料器脱气口。桨叶设计和工艺条件的某些组合显著增加了冲模填充不一致的风险(即片剂重量变化较大),因此限制了压片过程的效率。本研究中使用的方法能够比较桨叶设计在不同压片速度下的冲模填充性能,最终选择了一种最稳健的送料器设计,从而在较宽的产量范围内提供均匀的冲模填充。选择最稳健的参数是使旋转压片机作为灵活的单元操作的能力的重要前提。