Merck Healthcare KGaA, Department of Pharmaceutical Technologies, Darmstadt, Germany; Heinrich Heine University, Institute of Pharmaceutics and Biopharmaceutics, Universitätsstr. 1, Building 26.22, Düsseldorf, Germany.
Merck Healthcare KGaA, Department of Pharmaceutical Technologies, Darmstadt, Germany.
Int J Pharm. 2023 Jun 25;641:123052. doi: 10.1016/j.ijpharm.2023.123052. Epub 2023 May 15.
The aim of this study was to compare different scale-up strategies in twin-screw wet granulation and investigate the impact of the selected strategy on granule and tablet properties for a defined formulation. For the scale-up, a granulation process was transferred from a QbCon® 1 with a screw diameter of 16 mm to a QbCon® 25 line with a screw diameter of 25 mm. Three different scale-up strategies were introduced based on differences in process parameters and their resulting effects on various aspects. such as the powder feed number as a surrogate for the barrel fill level or the circumferential speed. Both are highly dependent on screw diameter and screw speed (SS), while the barrel fill level also depends on the overall throughput. Granules produced on the larger scale were significantly larger due to the larger gap size in the granulator, however, these differences were eliminated after milling. Despite major differences in powder feed number, circumferential speed, overall throughput and SS, product properties for both tablets and granules were strikingly similar after milling on both scales and with all applied strategies. For the selected formulation the effect of varying liquid to solid ratio at the same scale was much higher than the differences between scale-up strategies. The results of this study are promising for future process scale-up from lab scale to production scale in twin-screw wet granulation, as they are indicating towards a robust granulation process leading to similar tablet properties afterwards.
本研究旨在比较双螺杆湿法造粒中的不同放大策略，并研究所选策略对特定配方的颗粒和片剂性质的影响。为了放大，将 QbCon®1（螺杆直径为 16mm）中的造粒工艺转移到 QbCon®25 生产线（螺杆直径为 25mm）。基于工艺参数的差异及其对各个方面的影响，引入了三种不同的放大策略，例如粉末进料数作为桶填充水平的替代物或圆周速度。这两者都高度依赖于螺杆直径和螺杆速度（SS），而桶填充水平也取决于总吞吐量。由于造粒机中的间隙尺寸较大，较大规模生产的颗粒明显较大，但在研磨后这些差异被消除。尽管粉末进料数、圆周速度、总吞吐量和 SS 存在较大差异，但在两种规模上进行研磨后，两种片剂和颗粒的产品性质都非常相似，且所有应用的策略也是如此。对于选定的配方，在相同规模下改变液固比的效果比放大策略之间的差异要大得多。这项研究的结果对于未来从实验室规模到双螺杆湿法造粒生产规模的工艺放大具有很大的前景，因为它们表明造粒过程具有很强的稳健性，从而导致随后的片剂性质相似。
