Flowsheet optimization of an integrated continuous purification-processing pharmaceutical manufacturing operation
Flowsheet optimization of an integrated continuous purification-processing pharmaceutical manufacturing operation
复制标题
集成连续纯化加工制药生产操作的流程优化
DOI：
10.1016/j.ces.2013.07.035
复制
发表时间：
2013
影响因子：
4.7
通讯作者：
R. Ramachandran
中科院分区：
文献类型：
--
作者：
Maitraye Sen;A. Rogers;Ravendra Singh;A. Chaudhury;Joyce John;M. Ierapetritou;R. Ramachandran
在这项工作中，一个连续的API纯化过程已被优化使用的集成流程图模型。模拟本质上是动态的，包括API纯化步骤（结晶），然后过滤、干燥和API与辅料混合。对于第一次，这项研究表明，使用一个降阶模型（ROM）内的混合单元的颗粒速度的预测，再加上人口平衡模型（PBM）的混合器，以量化宏观性能。主要目标是优化集成流程图模型，以便在过程操作中有一个整体的改善。得到了结晶过程中的最佳冷却制度。确定了过滤器压力梯度、干燥气体温度和混合器转速的最佳值。可以看出，与非最佳操作条件相比，最佳操作条件使API晶体的CSD更窄，最终混合产物的RSD（相对标准偏差）更低。所开发的模型可以作为一个有效的工具，在控制和优化，并可以有未来的实施过程分析技术（PAT）系统的设计，可以导致改善操作的制造过程。
In this work, a continuous API purification process has been optimized using an integrated flowsheet model. The simulation is dynamic in nature and includes an API purification step (crystallization), followed by filtration, drying and mixing of the API with an excipient. For the first time, this study demonstrates the use of a reduced order model (ROM) within the mixing unit for prediction of particle velocities that is coupled with a population balance model (PBM) of the mixer to quantify macroscopic properties. The main objective is to optimize the integrated flowsheet model such that there is an overall improvement in process operation. The optimum cooling schedule during crystallization has been obtained. The optimum values of filter pressure gradient, drying gas temperature and mixer RPM (speed) have also been determined. It is seen that the optimized operating conditions give a narrower CSD of the API crystals and lower RSD (Relative standard deviation) of the final mixed product, compared to nonoptimal operating condition. The developed model can be used as an effective tool in control and optimization and can have future implementation in design of a Process Analytical Technology (PAT) system which can lead to improved operation of the manufacturing process.