多参数反馈调控结晶系统的开发及应用

文章导读

摘要结晶是一种重要的分离纯化单元操作，晶体的性质决定了医药产品的价值和用途。随着化工行业和医药行业的快速发展，传统的Trial-and-error结晶研究思路已不能满足其高效性、灵活性和经济性的需要。针对这一现状，结合多种过程分析技术，基于"质量来源于设计（Quality by design，QbD）"的新思路，自主开发了多参数反馈控制结晶系统，并分别以5'-核苷酸二钠和β-蒿甲醚为模型药物，考察了多参数反馈控制结晶系统在结晶过程动力学研究和建模中的应用。结果表明，研制的多参数反馈控制结晶系统对结晶过程的控制和机理描述具有指导意义，在制药领域具有良好的应用前景。

	Service

	把本文推荐给朋友
	加入我的书架
	加入引用管理器
	Email Alert
	RSS
	作者相关文章
	刘诗苑
	李炳辉
	唐凯
	孙良杰
	韦桂璇
	江燕斌

关键词：药物结晶反馈调节过程分析技术结晶动力学

Abstract： Crystallization is an important separation and purification unit operation, and the nature of crystals determines the value and use of pharmaceutical products. With the rapid development of the chemical industry and the pharmaceutical industry, the traditional trial-and-error crystallization research ideas can no longer meet the needs of efficiency, flexibility and economy. In view of this situation, based on the new idea of "Quality by Design (QbD)" and combined with a variety of process analysis techniques, this study independently developed a multi-parameter feedback control system for crystallization. Disodium 5'-ribonucleotide and β-artemether were used as model respectively. The application of the multi-parameter feedback control system in the kinetic study and modeling of the crystallization process has been investigated. The results show that the multi-parameter feedback control system not only has guiding significance for the control of crystallization process and the elaboration of crystallization mechanism, but also has good application prospects in the pharmaceutical field.

Keywords： crystallization of drug feedback control process analysis technologies crystallization kinetics

Received 2022-11-08;

Fund:国家自然科学基金（22178121）。

Corresponding Authors: 江燕斌,教授,E-mail:cebjiang@scut.edu.cn。 Email: cebjiang@scut.edu.cn

About author: 刘诗苑(1992-),女,博士,助理研究员,现从事结晶科学与工程方面的研究。

引用本文:

刘诗苑, 李炳辉, 唐凯, 孙良杰, 韦桂璇, 江燕斌.多参数反馈调控结晶系统的开发及应用[J]. 化学工业与工程, 2023,40(1): 60-71

LIU Shiyuan, LI Binghui, TANG Kai, SUN Liangjie, WEI Guixuan, JIANG Yanbin.Development and application of multi-parameter feedback control system for crystallization[J]. Chemcial Industry and Engineering, 2023,40(1): 60-71

[1] LOH N D, SEN S, BOSMAN M, et al. Multistep nucleation of nanocrystals in aqueous solution[J]. Nature Chemistry, 2017, 9(1):77-82
[2] SOSSO G C, CHEN J, COX S J, et al. Crystal nucleation in liquids:Open questions and future challenges in molecular dynamics simulations[J]. Chemical Reviews, 2016, 116(12):7078-7116
[3] WANTHA L. Kinetics of the solution-mediated polymorphic transformation of organic compounds[J]. Current Pharmaceutical Design, 2018, 24(21):2383-2393
[4] 邢晓红, 欧阳金波, 周利民, 等. 限域空间内的结晶研究进展[J]. 化学工业与工程, 2022, 39(5):39-48 XING Xiaohong, OUYANG Jinbo, ZHOU Limin, et al. Research progress of crystallization in confined space[J]. Chemical Industry and Engineering, 2022, 39(5):39-48(in Chinese)
[5] SZILÁGYI B, BORSOS Á, PAL K, et al. Experimental implementation of a Quality-by-Control (QbC) framework using a mechanistic PBM-based nonlinear model predictive control involving chord length distribution measurement for the batch cooling crystallization of L-ascorbic acid[J]. Chemical Engineering Science, 2019, 195:335-346
[6] ZHANG T, SZILÁGYI B, GONG J, et al. Novel semibatch supersaturation control approach for the cooling crystallization of heat-sensitive materials[J]. AIChE Journal, 2020, doi:10.1002/aic.16955
[7] LIONBERGER R A, LEE S L, LEE L M, et al. Quality by design:Concepts for ANDAs[J]. The AAPS Journal, 2008, 10(2):268-276
[8] KACKER R, SALVADOR P M, STURM G S J, et al. Microwave assisted direct nucleation control for batch crystallization:Crystal size control with reduced batch time[J]. Crystal Growth & Design, 2016, 16(1):440-446
[9] BÖTSCHI S, RAJAGOPALAN A K, MORARI M, et al. Feedback control for the size and shape evolution of needle-like crystals in suspension. I. concepts and simulation studies[J]. Crystal Growth & Design, 2018, 18(8):4470-4483
[10] YANG Y, PAL K, KOSWARA A, et al. Application of feedback control and in situ milling to improve particle size and shape in the crystallization of a slow growing needle-like active pharmaceutical ingredient[J]. International Journal of Pharmaceutics, 2017, 533(1):49-61
[11] 赵绍磊, 王灵宇, 吴送姑. 药物多晶型的研究进展[J]. 化学工业与工程, 2018, 35(3):12-21 ZHAO Shaolei, WANG Lingyu, WU Songgu. Progress in the research of pharmaceutical polymorph[J]. Chemical Industry and Engineering, 2018, 35(3):12-21(in Chinese)
[12] 李炳辉. 基于实时监测的5'-呈味核苷酸二钠反溶剂结晶过程研究[D]. 广州:华南理工大学, 2019 LI Binghui. The study of disodium 5'-ribonucleotide anti-solvent crystallization based on real-time monitoring platform[D]. Guangzhou:South China University of Technology, 2019 (in Chinese)
[13] 唐凯. 多参数反馈调控结晶系统的初步开发[D]. 广州:华南理工大学, 2014 TANG Kai. Primary development of multi-parameter feedback regulation and control system for crystallization[D]. Guangzhou:South China University of Technology, 2014 (in Chinese)
[14] NAGY Z K, FUJIWARA M, BRAATZ R D. Modelling and control of combined cooling and antisolvent crystallization processes[J]. Journal of Process Control, 2008, 18(9):856-864
[15] ABU BAKAR M R, NAGY Z K, SALEEMI A N, et al. The impact of direct nucleation control on crystal size distribution in pharmaceutical crystallization processes[J]. Crystal Growth & Design, 2009, 9(3):1378-1384
[16] SALEEMI A N, RIELLY C D, NAGY Z K. Comparative investigation of supersaturation and automated direct nucleation control of crystal size distributions using ATR-UV/vis spectroscopy and FBRM[J]. Crystal Growth & Design, 2012, 12(4):1792-1807
[17] SALEEMI A, RIELLY C, NAGY Z K. Automated direct nucleation control for in situ dynamic fines removal in batch cooling crystallization[J]. CrystEngComm, 2012, 14(6):2196-2203
[18] SIMONE E, SALEEMI A N, TONNON N, et al. Active polymorphic feedback control of crystallization processes using a combined Raman and ATR-UV/vis spectroscopy approach[J]. Crystal Growth & Design, 2014, 14(4):1839-1850
[19] FALOLA A, BORISSOVA, A, WANG, X. Extended method of moment for general population balance models including size dependent growth rate, aggregation and breakage kernels[J]. Computers & Chemical Engineering, 2013, 56:1-11
[20] LI B, SONG Y, SUN L, et al. Measurement of disodium 5'-inosinate and disodium 5'-guanylate in aqueous ethanol by attenuated total reflection ultraviolet method[J]. Chemical Engineering & Technology, 2019, 42(11):2376-2385
[21] ZHAO W, LI B, LIU S, et al. Kinetic study of complicated anti-solvent and cooling crystallization of disodium 5'-ribonucleotide[J]. Particuology, 2023, 73:103-112
[22] BRAATZ R D. Advanced control of crystallization processes[J]. Annual Reviews in Control, 2002, 26(1):87-99
[23] TRIFKOVIC M, SHEIKHZADEH M, ROHANI S. Multivariable real-time optimal control of a cooling and antisolvent semibatch crystallization process[J]. AIChE Journal, 2009, 55(10):2591-2602
[24] FUJIWARA M, NAGY Z K, CHEW J W, et al. First-principles and direct design approaches for the control of pharmaceutical crystallization[J]. Journal of Process Control, 2005, 15(5):493-504
[25] SUN L, SONG Y, LI B, et al. A modified method for modelling, optimization and control of an anti-solvent crystallization process[J]. Chemical Engineering Science, 2020, doi:10.1016/j.ces.2019.115253
[26] WÄCHTER A, BIEGLER L T. On the implementation of an interior-point filter line-search algorithm for large-scale nonlinear programming[J]. Mathematical Programming, 2006, 106(1):25-57