PromisLab, School of Pharmacy, University of Eastern Finland, 70211 Kuopio, Finland; iMed.ULisboa, Faculty of Pharmacy, University of Lisbon, 1649-003 Lisbon, Portugal.
PromisLab, School of Pharmacy, University of Eastern Finland, 70211 Kuopio, Finland.
Int J Pharm. 2023 May 25;639:122969. doi: 10.1016/j.ijpharm.2023.122969. Epub 2023 Apr 20.
In this study, an integrated flowsheet model of the continuous feeder-mixer system was calibrated, simulated and compared against experimental data. The feeding process was first investigated using two major components (ibuprofen and microcrystalline cellulose (MCC)), in a formulation comprised of: 30 wt% of ibuprofen, 67.5 wt% MCC, 2 wt% of sodium starch glycolate and 0.5 wt% of magnesium stearate. The impact of a refill on feeder performance was experimentally evaluated for different operating conditions. Results showed that it had no influence on feeder performance. While simulations with the feeder model fairly reproduced the material behaviour observed in the feeder, unintended disturbances were underpredicted due to the model's low complexity. Experimentally, mixer's efficiency was assessed based on ibuprofen residence time distribution. Mean residence time pointed to a higher mixer's efficiency at lower flow rates. Blend homogeneity results showed that for the entire set of experiments, ibuprofen RSD < 5%, irrespective of process variables. A feeder-mixer flowsheet model was calibrated, after regressing the axial model coefficients. The regression curves exhibited a R above 0.96, whereas the RMSE varied from 1.58x10 to 1.06x10 s across all fitted curves. Simulations confirmed that flowsheet model captured the powder dynamics inside the mixer and qualitatively predicted the mixer's filtering ability against feeding composition fluctuations, as well as ibuprofen RSD in blend, in line with real experiments.
在这项研究中,我们对连续给料-混合系统的综合流程图模型进行了校准、模拟,并与实验数据进行了比较。首先,我们使用两种主要成分(布洛芬和微晶纤维素(MCC))研究了给料过程,配方由以下成分组成:30wt%布洛芬、67.5wt% MCC、2wt%交联羧甲基纤维素钠和 0.5wt%硬脂酸镁。为不同的操作条件,我们实验评估了补充料对给料器性能的影响。结果表明,它对给料器性能没有影响。虽然给料器模型的模拟很好地再现了给料器中观察到的物料行为,但由于模型的低复杂性,对意外干扰的预测不足。在实验中,我们基于布洛芬停留时间分布评估了混合器的效率。平均停留时间表明,在较低流速下,混合器的效率更高。混合均匀度结果表明,对于整个实验集,布洛芬的 RSD<5%,与工艺变量无关。在回归轴向模型系数后,我们对给料-混合器流程图模型进行了校准。回归曲线的 R 均大于 0.96,而所有拟合曲线的 RMSE 均在 1.58x10 到 1.06x10 s 之间变化。模拟结果证实,该流程图模型能够捕捉混合器内的粉末动力学,并定性地预测混合器对给料成分波动的过滤能力,以及混合中布洛芬的 RSD,与实际实验一致。