A bubble column was investigated as a method to achieve a desired and controllable rate of evaporation of a pharmaceutical solution. Applying a thermodynamic model to predict the rate of evaporation, all predicted values were observed to have accuracies within the bounds of instrumentation errors (<5% absolute). The developed model accounted for the measured effect of reduced vapor pressure, caused by the dissolved solids as a function of their concentration. A general method to obtain accurate measurement of this effect is introduced and applied, improving the accuracy of model predictions. Consistent and repeatable evaporation rates ranging from 0.7 to 6.9 g/min were achieved experimentally, and errors between predicted rates and observed ranged from 0.219% to 4.19% absolute. This demonstrates a controllable and flexible method for the evaporation of process streams which can be compared to harsher conventional methods such as boiling. The column was configured in a continuous mode and coupled to a downstream crystallizer (MSMPR). Using the column as a controllable concentrator, the concentration of a dilute feed stream of paracetamol in methanol was increased in a single equilibrium stage. The column demonstrated the ability to concentrate the solution in flow by 179%, delivering a flow of 2 ml/min of concentrated liquor to the MSMPR. The MSMPR achieved steady-state of control, measured by offline dissolved concentration analysis and particle count by FBRM in situ, highlighting the applicablity of the column to perform reliably in a continuous tandem.

中文翻译：

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结晶前 API 溶液流连续蒸发系统的开发

鼓泡塔被研究作为实现药物溶液的期望且可控的蒸发速率的方法。应用热力学模型来预测蒸发率，观察到所有预测值的准确度都在仪器误差范围内（<5% 绝对值）。开发的模型考虑了由溶解固体引起的蒸气压降低的测量影响，作为其浓度的函数。介绍并应用了一种获得这种效应的准确测量的通用方法，从而提高了模型预测的准确性。通过实验实现了范围从 0.7 到 6.9 克/分钟的一致且可重复的蒸发速率，预测速率与观察到的绝对误差范围为 0.219% 到 4.19%。这证明了一种可控且灵活的工艺流蒸发方法，可与更苛刻的传统方法（如煮沸）进行比较。色谱柱配置为连续模式，并连接到下游结晶器 (MSMPR)。使用该柱作为可控浓缩器，在单个平衡阶段中提高了甲醇中稀释的扑热息痛进料流的浓度。该柱展示了将流动溶液浓缩 179% 的能力，将 2 ml/min 的浓缩液流量输送到 MSMPR。通过离线溶解浓度分析和 FBRM 原位颗粒计数测量，MSMPR 实现了稳态控制，突出了色谱柱在连续串联中可靠运行的适用性。