溶析结晶过程的混合模型与耦合模拟

Antisolvent crystallization is greatly affected by the micro-mixing effect, making the scale-up and control of the size and crystal size distribution (CSD) very difficult. Tha accuracy and the physical background of the widely used micromixing model, i.e., the finite-mode probability density function (FM-PDF), is inadequate. In the current project, on the basis of the existing single-phase DQMOM-IEM (direct quadrature method of moments coupled with the interaction by exchange with the mean) micromixing model, the mechanisms of multiphase turbulence and transport and the polulation balace equation (PBE), a coulped model, i.e., the CFD-DQMOM-IEM-PBE, will be developed for the processes of antisolvent crystallization. Experiments on the antisolvent crystallization are conducted for the systems of NaCl-water-ethanol and paracetamol-water-acetone. Crystal size distribution (CSD) and the distribution of the solid fraction are measured with on-line techniques. The experimental data are used to validate the reliability and applicability of the model. The influence of some important factors such as operating parameters, the internals and the type of the impeller on the micro-mixing in an antisolvent crystallization system is numerically investigated with the two-phase CFD-DQMOM-IEM-PBE model. The results might be useful for the processes of antisolvent crystallization such as NaCl-water-ethanol, paracetamol-water-acetone etc. for the design, control and scale-up of crystallizers. One-dimensional PBE is being used in the crystallization simulation of actual processes (heterogeneous systems), thus the morphology cannot be predicted. Numerical diffusion and the limited applicability are the two major problems for the available techniques for solving the multi-dimensional PBE with the discrete schemes. Based on our previous work on the general discretized one-dimensional PBE, the corresponding two-dimensional form will be developed in this project and it can hopefully predict simultaneously the size and crystal habit in real crystallization processes in the near future.

医药等工业中应用广泛的溶析结晶过程，混合效应明显、放大效应显著，晶体大小与分布(CSD)调控困难。现有的有限节点PDF微观混合模型的精度和模型的物理背景还很欠缺。本项目基于单相DQMOM-IEM微观混合模型，结合多相流体力学(CFD)与溶析结晶过程的粒数衡算方程(PBE)，并考虑结晶二次过程，建立两相微观混合、流动与溶析结晶全过程的多尺度耦合模型，即CFD-DQMOM-IEM-PBE。实验以扑热息痛-水-丙酮、NaCl-水-乙醇为对象，实时在线获得体系的CSD与相含率分布。模拟揭示操作条件等对晶体大小和CSD的影响规律，指导扑热息痛等溶析结晶过程的工程设计放大。目前实际结晶过程（非均相）的模拟PBE均为一维，无法预测晶体形貌。现有基于均相的多维PBE离散求解存在数值扩散大、应用灵活性受限等问题。将基于我们建立的一维通用离散化PBE，扩展应用于二维，有望用于药物结晶过程大小与形貌的同时预测。

医药等工业中应用广泛的溶析结晶过程，混合效应明显、放大效应显著，晶体大小与分布(CSD)调控困难。本基金课题的主要研究内容为：(a) 溶析结晶过程耦合模型与数值模拟；(b) 搅拌槽结晶过程的在线实验测量；(c) 通用二维PBE建立与一维生长动力学二维分解； (d) 气液CFD-PBE模拟与OpenFOAM求解器开发; (e)高压鼓泡塔CFD-PBE模型与模拟; (f) 气升式环流结晶器模型与数值模拟。本课题研究取得的主要进展为：(1) 建立了两相多环境微观混合模型，建立了通用的KT高精度有限体积中心差分格式并离散PBE，耦合两相CFD，建立了溶析结晶过程两相CFD-Micromixing-PBE耦合模型，并开发了OpenFOAM源代码求解器，对洛伐他丁-甲醇-水溶析结晶过程进行了模拟，获得了操作参数对晶体大小与CSD的影响规律; (2) 基于我们开发的一维通用KT高精度离散格式， 发展了其二维形式并建立了二维离散PBE。 基于常见的针状形貌晶体，推导了其一维与二维生长动力学的一般关联式，并根据一维与二维尺寸之间不同关系对方法进行了验证； (3) 基于开源软件OpenFOAM，采用cell average求解PBE，开发了通用的气液两相CFD-PBE求解器，对鼓泡塔中的气液流动进行模拟。同时气液两相流的模型进行修正，开发了相应的适用于常压到高压操作范围的OpenFOAM求解器，模拟结果很好的表明了压力对气液流动的影响规律; (4) 建立了环流结晶过程CFD-PBE-PBE耦合模型，并开发了相应的OpenFOAM求解器，对环流反应器内CO2溶于Ca(OH)2溶液生成CaCO3沉淀的过程成功进行了模拟。溶析结晶过程耦合模型以及开发的二维PBE有望用于混合影响显著的快速结晶过程的粒径与形貌的同时预测，辅助过程优化与设计。开发的气液CFD-PBE求解器可用于工业操作条件(高温与高压)的气液反应器设计。而环流结晶过程耦合模型与OpenFOAM求解器有望用于一些较特殊结晶过程与结晶器(气体驱动替代搅拌桨，大幅减少晶体磨损导致的二次成核)的设计。