Bekaert B, Grymonpré W, Novikova A, Vervaet C, Vanhoorne V
Laboratory of Pharmaceutical Technology, Department of Pharmaceutics, Ghent University, Ottergemsesteenweg 460, B-9000 Ghent, Belgium.
Fette Compacting Belgium, Schaliënhoevedreef 1 b, B-2800 Mechelen, Belgium.
Int J Pharm. 2022 Feb 5;613:121421. doi: 10.1016/j.ijpharm.2021.121421. Epub 2021 Dec 23.
In this study, quantitative relationships were established between blend properties, process settings and blending responses via multivariate data-analysis. Four divergent binary blends were composed in three different ratios and processed at various throughputs and impeller speeds. Additionally, different impeller configurations were tested to see their impact on the overall blending performance. During each run, feeder mass flows were compared with the API concentration (BU) in order to investigate the dampening potential of the blender. The blender hold-up mass (HM), mean residence time (MRT), strain on the powder (#BP) and BU variability (RSD) were determined as blending descriptors and analyzed via PLS-regression. This elucidated the correlation between process settings (i.e. throughput and impeller speed) and blending responses, as well as the impact of blend properties on MRT and RSD. Furthermore, the study revealed that HM does not need to be in steady state conditions to assure a stable BU, while it became clear that long/large feeder deviations can only be dampened by the blender when using dedicated impeller configurations. Overall, this study demonstrated the generic application of the blender, while the developed PLS models could be used to predict the blender performance based on the blend properties.
在本研究中,通过多变量数据分析建立了共混物特性、工艺设置和共混响应之间的定量关系。以三种不同比例组成了四种不同的二元共混物,并在不同的产量和叶轮转速下进行加工。此外,还测试了不同的叶轮配置,以观察它们对整体共混性能的影响。在每次运行过程中,将进料器质量流量与活性药物成分浓度(含量单位)进行比较,以研究混合器的缓冲潜力。确定混合器的滞留质量(HM)、平均停留时间(MRT)、粉末应变(#BP)和含量单位变异性(相对标准偏差)作为共混描述符,并通过偏最小二乘回归进行分析。这阐明了工艺设置(即产量和叶轮转速)与共混响应之间的相关性,以及共混物特性对平均停留时间和相对标准偏差的影响。此外,研究表明,混合器的滞留质量无需处于稳态条件即可确保含量单位稳定,同时还明确了只有在使用专用叶轮配置时,混合器才能抑制大的进料偏差。总体而言,本研究证明了该混合器的广泛适用性,而所开发的偏最小二乘模型可用于根据共混物特性预测混合器性能。