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Mathematical modelling and analysis of an industrial scale evaporative crystallizer producing lactose monohydrate

机译:工业规模生产一水合乳糖蒸发结晶器的数学建模与分析

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Lactose is industrially produced by a series of concentration steps to supersaturate the solution allowing crystallization to take place. This papers deals with the operation and analysis of a forced circulation evaporative crystallizer producing pharmaceutical lactose. A mathematical model of the operation of the crystallizer was developed. The model comprises of the mass balance, population balance, nucleation kinetics, growth kinetics and lactose solubility and mutarotation rate expressions. The steady state operation of the crystallizer was analysed from the classical mixed suspension mixed product removal (MSMPR) model perspective. It was found that the crystallizer behaviour deviated from ideal MSMPR behaviour with a steep upward curvature in the population density curve for crystal sizes below 40 μm. A size dependent growth (SDG) rate model was used to model the deviation from ideal behaviour. The parameters of the SDG model were estimated by fitting it to the measured population density curve from the crystallizer. The crystallization kinetic parameters like growth and nucleation rate constants were then estimated by fitting the simulated trends to the measured date. The model showed that the average crystal size follows a transient decaying dynamics before settling down to a constant value. This was reflected in the actual data collected from the crystallizer. The transient dynamics disappeared from the model results when a simple size independent growth model was used.
机译:乳糖是通过一系列浓缩步骤在工业上生产的,以使溶液过饱和,从而发生结晶。本文研究了强制循环蒸发结晶器生产药用乳糖的操作和分析。建立了结晶器操作的数学模型。该模型包括质量平衡,群体平衡,成核动力学,生长动力学以及乳糖溶解度和诱变速率表达。从经典混合悬浮液混合产物去除(MSMPR)模型的角度分析了结晶器的稳态运行。已发现,对于小于40μm的晶体,结晶器行为偏离了理想的MSMPR行为,其种群密度曲线呈陡峭的向上弯曲。使用大小依赖性增长(SDG)速率模型来建模与理想行为的偏差。通过将SDG模型的参数拟合到结晶器中测得的人口密度曲线,可以估算出SDG模型的参数。然后通过将模拟趋势拟合到测量日期来估算结晶动力学参数(如生长和成核速率常数)。该模型表明,平均晶体尺寸遵循瞬态衰减动力学,然后稳定到恒定值。这反映在从结晶器收集的实际数据中。当使用简单的尺寸无关的生长模型时,瞬态动力学从模型结果中消失。

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