固液两相流微观混合与热质传递对连续结晶过程的协同强化机理研究

Continuous crystallization has become the new focus of technology competitions and intellectual property protections in the future pharmaceutical industries, however, it is still not clear that the cooperation and enhancement mechanisms for the micro-mixing and the heat-mass transfer in the solid-liquid two-phase flow on continuous crystallization process, especially nucleation and crystal growth. Taking Oscillatory Baffled Crystallizer (OBC) as the research object, theoretical analysis, experiments and Computational Fluid Dynamics (CFD) simulation will be employed to study the effects of baffle types and geometries of OBCs and the operation conditions (oscillatory frequencies and amplitudes) on the velocity distribution, Residence Time Distribution (RTD) and Crystal Size Distribution (CSD) in continuous OBCs. The discrete CFD-PDF-PBE models for continuous crystallizations will be established by integrating the Probability Density Function (PDF), the oscillatory Reynolds number (Reo), the Strouhal number (St), RTD, etc., which characterizing the micro-mixing in OBCs, into the Population Balance Equation (PBE), together with the Nusselt number (Nu), diffusion coefficient (D), mass transfer coefficient (kd) etc. that characterizing heat-mass transfer, and then the cooperation and enhancement mechanisms for micro-mixing, heat-mass transfer in the solid-liquid two-phase flow on continuous crystallization process will be discussed. Based on the above research achievements, novel and high-efficient continuous OBCs will be developed to ensure the tailored control and optimization of CSD, crystal habit and purity in continuous crystallization process. The work of this project will surely contribute to deep understandings on the separation processes cooperated by micro-mixing and heat-mass transfer, and provide the theoretical basis and practical evidence for the development, modification and optimization of new continuous crystallizers.

连续结晶是制药工业未来技术竞争和产业保护的新焦点，但固液两相流的微观混合、热质传递与结晶过程(成核与晶体生长)协同强化机理还不明确。本项目拟以连续振荡流挡板结晶器(OBC)为研究对象，采用理论分析、实验以及CFD模拟，研究不同OBC挡板类型与几何结构、振荡条件(振幅与频率)等对连续OBC内固液两相流场速度分布、停留时间分布(RTD)、晶体粒度分布(CSD)的影响规律，通过将表征微观混合的概率密度函数(PDF)、振荡雷诺数、斯特劳哈尔数、RTD等，以及表征热质传递的努塞尔数、传质系数等参数关联进入结晶过程粒数衡算方程(PBE)，建立离散化的CFD-PDF-PBE耦合数学模型，阐明连续结晶过程固液两相流微观混合、热质传递与结晶过程的协同强化机理，开发新型高效的连续OBC，实现连续结晶产品粒度、晶习及纯度的定向调控，为新型连续结晶器及其相关工艺的开发、改造、优化以及工业化提供理论基础和实践依据。

连续结晶是制药工业未来技术竞争和产业保护的新焦点，而连续振荡流挡板结晶器(Continuous Oscillatory Baffled Crystallizer，COBC)已成为药物连续结晶过程工业应用和设备优化升级的热点和前沿。虽然COBC在不同药物结晶体系的工艺开发、优化以及宏观调控方面已经取得了丰富的成果，但COBC固-液两相流微观混合、热-质传递与结晶过程(成核与晶体生长)协同强化机理还不明确。.本项目围绕结晶热力学、COBC几何构型优化、固-液两相流微观混合、热-质传递与结晶过程耦合强化理论和应用基础取得了系统性科研成果，在Chem. Eng. Sci., CrystEngComm., J. Mol. Liq.等国内外权威期刊发表论文共计12篇；申请国家发明专利6项，授权国家发明专利2项并完成了专利权转让、授权新型专利5项。.以项目组成员为核心骨干，组建了武汉科技大学化工与功能材料研究团队，引进优秀青年人才3名，新增2人荣获湖北省“楚天学子”人才项目资助，2人荣获“武汉英才（优秀青年人才）人才项目资助，1人晋升为教授，2人晋升为副教校，培养博士研究生2名，硕士研究生8名。.同时，积极开展学术交流和国际合作，2019年在武汉科技大学举办“2019晶体工程&先进材料”国际前沿论坛（IFCEAM 2019）；项目组成员累计参加国际/国内重要学术会议15次，其中大会邀请报告8次。.本项目研发的新型COBC，以及建立的基于COBC构型对连续OBC内热-质传递与结晶过程协同强化的新理论和新应用技术，已完成氯氮平、赤藓糖醇、头孢曲松钠等实验室小试，有望促进我国化工、医药及相关产业的技术发展。