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Flowsheet Modelling of a Powder Continuous Feeder-Mixer System.

International journal of pharmaceutics(2023)

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摘要
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 feedermixer flowsheet model was calibrated, after regressing the axial model coefficients. The regression curves exhibited a R2 above 0.96, whereas the RMSE varied from 1.58x10-4 to 1.06x10-3 s-1 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.
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关键词
Continuous manufacturing,Flowsheet modeling,Residence time distribution,Continuous feeding,Continuous blending,Near -infrared spectroscopy
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