Ultrasound assisted crystallization of cephalexin monohydrate: Nucleation mechanism and crystal habit control

doi:10.1016/j.cjche.2021.07.034

中国化学工程学报 ›› 2022, Vol. 41 ›› Issue (1): 430-440.DOI: 10.1016/j.cjche.2021.07.034

• Chemical Engineering Thermodynamics • 上一篇下一篇

Ultrasound assisted crystallization of cephalexin monohydrate: Nucleation mechanism and crystal habit control

Zeren Shang¹, Mingchen Li¹, Baohong Hou¹, Junli Zhang^1,2, Kuo Wang¹, Weiguo Hu^1,2, Tong Deng¹, Junbo Gong¹, Songgu Wu¹

1 School of Chemical Engineering and Technology, State Key Laboratory of Chemical Engineering, Tianjin University, Tianjin 300072, China;
2 North China Pharmaceutical Co., Ltd., Shijiazhuang 050015, China

收稿日期:2021-05-07 修回日期:2021-07-21 出版日期:2022-01-28 发布日期:2022-02-25
通讯作者: Baohong Hou,E-mail address:houbaohong@tju.edu.cn;Songgu Wu,E-mail address:wusonggu@tju.edu.cn
基金资助:
The authors are grateful to the financial support of National Natural Science Foundation of China (22078238) and Special Project for the Transformation of Major Scientific and Technology Achievements of Hebei Province (19042822Z).

Ultrasound assisted crystallization of cephalexin monohydrate: Nucleation mechanism and crystal habit control

Zeren Shang¹, Mingchen Li¹, Baohong Hou¹, Junli Zhang^1,2, Kuo Wang¹, Weiguo Hu^1,2, Tong Deng¹, Junbo Gong¹, Songgu Wu¹

1 School of Chemical Engineering and Technology, State Key Laboratory of Chemical Engineering, Tianjin University, Tianjin 300072, China;
2 North China Pharmaceutical Co., Ltd., Shijiazhuang 050015, China

Received:2021-05-07 Revised:2021-07-21 Online:2022-01-28 Published:2022-02-25
Contact: Baohong Hou,E-mail address:houbaohong@tju.edu.cn;Songgu Wu,E-mail address:wusonggu@tju.edu.cn
Supported by:
The authors are grateful to the financial support of National Natural Science Foundation of China (22078238) and Special Project for the Transformation of Major Scientific and Technology Achievements of Hebei Province (19042822Z).

摘要/Abstract

摘要： With the high-quality requirements for cephalexin monohydrate, developing a robust and practical crys-tallization process to produce cephalexin monohydrate with good crystal habit, appropriate aspect ratio and high bulk density as well as suitable flowability is urgently needed. This research has explored the influence of ultrasound on crystallization of cephalexin monohydrate in terms of nucleation mechanism and crystal habit control. The results of metastable zone width and induction time measurement showed the presence of ultrasound irradiation can narrow the metastable zone and shorten induction time. Cavitation phenomena generated by ultrasound were used to qualitatively explain the mechanism of ultrasound promoting nucleation of cephalexin monohydrate. Furthermore, on the basis of classical nucleation theory and induction time data, a series of nucleation-related parameters (such as crystal-liquid interfacial tension, radius of the critical nucleus and etc.) were calculated and showed a decreasing trend under ultrasound irradiation. The diffusion coefficient of the studied system was also determined to increase by 72.73% under ultrasound. The changes in these parameters have quantitatively confirmed the mechanism of ultrasound influence on the nucleation process. In further, the calculated surface entropy factor has confirmed that the growth of cephalexin monohydrate follows continuous growth mechanism under the research conditions of this work. Through the exploration of crystallization conditions, it is found that suitable ultrasonic treatment, seeding, supersaturation control and removal of fine crystals are conducive to improving the quality of cephalexin monohydrate product. Optimizing the crystallization process coupled continuous ultrasound irradiation with fine-crystal dissolution policy has achieved the controllable production of monodisperse cephalexin monohydrate crystal with good performance.

关键词: Cephalexin monohydrate, Sonocrystallization, Nucleation kinetics, Fine-crystal dissolution policy, Crystal habit control

Abstract: With the high-quality requirements for cephalexin monohydrate, developing a robust and practical crys-tallization process to produce cephalexin monohydrate with good crystal habit, appropriate aspect ratio and high bulk density as well as suitable flowability is urgently needed. This research has explored the influence of ultrasound on crystallization of cephalexin monohydrate in terms of nucleation mechanism and crystal habit control. The results of metastable zone width and induction time measurement showed the presence of ultrasound irradiation can narrow the metastable zone and shorten induction time. Cavitation phenomena generated by ultrasound were used to qualitatively explain the mechanism of ultrasound promoting nucleation of cephalexin monohydrate. Furthermore, on the basis of classical nucleation theory and induction time data, a series of nucleation-related parameters (such as crystal-liquid interfacial tension, radius of the critical nucleus and etc.) were calculated and showed a decreasing trend under ultrasound irradiation. The diffusion coefficient of the studied system was also determined to increase by 72.73% under ultrasound. The changes in these parameters have quantitatively confirmed the mechanism of ultrasound influence on the nucleation process. In further, the calculated surface entropy factor has confirmed that the growth of cephalexin monohydrate follows continuous growth mechanism under the research conditions of this work. Through the exploration of crystallization conditions, it is found that suitable ultrasonic treatment, seeding, supersaturation control and removal of fine crystals are conducive to improving the quality of cephalexin monohydrate product. Optimizing the crystallization process coupled continuous ultrasound irradiation with fine-crystal dissolution policy has achieved the controllable production of monodisperse cephalexin monohydrate crystal with good performance.

Key words: Cephalexin monohydrate, Sonocrystallization, Nucleation kinetics, Fine-crystal dissolution policy, Crystal habit control

Zeren Shang, Mingchen Li, Baohong Hou, Junli Zhang, Kuo Wang, Weiguo Hu, Tong Deng, Junbo Gong, Songgu Wu. Ultrasound assisted crystallization of cephalexin monohydrate: Nucleation mechanism and crystal habit control[J]. 中国化学工程学报, 2022, 41(1): 430-440.

参考文献

[1] Committee of National Pharmacopoeia, Chinese Pharmacopoeia 2015 Edition, China Medical Science Press, Beijing, 2015.
[2] M.A. Hoque, M.M. Rahman, M.M. Alam, S. Mahbub, M.A. Khan, D. Kumar, M.D. Albaqami, S.M. Wabaidur, Interaction of cephalexin monohydrate with surfactants in aqueous and sodium chloride solution at variable temperatures: Conductivity and spectroscopic measurements, J. Mol. Liq. 326(2021) 115337.
[3] Ministry of Industry and Information Technology of the People’s Republic of China, 2018 China Pharmaceutical Statistics Annual Report, Ministry of Industry and Information Technology of the People’s Republic of China, Beijing, 2019.
[4] S. Li, X. Cao, Enzymatic synthesis of Cephalexin in recyclable aqueous twophase systems composed by two pH responsive polymers, Biochem. Eng. J. 90(2014) 301–306.
[5] M. Li, Z. Shang, B. Hou, Optimizing the aspect ratio of cephalexin in reactive crystallization by controlling supersaturation and seeding policy, Trans. Tianjin Univ. 25(4) (2019) 348–356.
[6] N. Wei, L. Jia, Z. Shang, J. Gong, S. Wu, J. Wang, W. Tang, Polymorphism of levofloxacin:Structure, properties and phase transformation, CrystEngComm 21(41) (2019) 6196–6207.
[7] S. Jin, M. Chen, Z. Li, S. Wu, S. Du, S. Xu, S. Rohani, J. Gong, Design and mechanism of the formation of spherical KCl particles using cooling crystallization without additives, Powder Technol. 329(2018) 455–462.
[8] Z.R. Shang, L.N. Jia, M.C. Li, W.G. Hu, Y.X. Zhao, X.Y. Wang, S.G. Wu, Solution thermodynamic analysis of p-(aminomethyl)benzoic acid in four binary solvents from 288.15 to 328.15 K, J. Chem. Eng. Data 63(12) (2018) 4720–4734.
[9] N. Wei, Z.R. Shang, Y.M. Ma, N.Y. Zhang, J.B. Gong, W.W. Tang, Experimental determination and prediction of the solubility of alpha-(trichloromethyl) benzyl acetate in monosolvents and binary mixed solvents, J. Mol. Liq. 294(2019) 111633.
[10] M.Y. Chen, D.J. Zhang, W.B. Dong, Z.L. Luo, C. Kang, H.C. Li, G. Wang, J.B. Gong, Amorphous and humidity caking: a review, Chin. J. Chem. Eng. 27(6) (2019) 1429–1438.
[11] M.A. McDonald, G.D. Marshall, A.S. Bommarius, M.A. Grover, R.W. Rousseau, Crystallization kinetics of cephalexin monohydrate in the presence of cephalexin precursors, Cryst. Growth Des. 19(9) (2019) 5065–5074.
[12] J.L. Zhang, J.B. Gong, H. Sun, Z.G. Duan, W.G. Hu, Study and application of the continuous crystallization process of cefalexin, Chem. Ind. Eng. Prog. 38(7) (2019) 3349–3354.
[13] H. Salami, C.E. Lagerman, P.R. Harris, M.A. McDonald, A.S. Bommarius, R.W. Rousseau, M.A. Grover, Model development for enzymatic reactive crystallization of b-lactam antibiotics: a reaction–diffusion-crystallization approach, React. Chem. Eng. 5(11) (2020) 2064–2080.
[14] S. Nalesso, M.J. Bussemaker, R.P. Sear, M. Hodnett, J. Lee, A review on possible mechanisms of sonocrystallisation in solution, Ultrason. Sonochem. 57(2019) 125–138.
[15] L.M. Belca, A. Ručigaj, D. Teslič, M. Krajnc, The use of ultrasound in the crystallization process of an active pharmaceutical ingredient, Ultrason. Sonochem. 58(2019) 104642.
[16] J. Li, Y. Bao, J. Wang, Effects of sonocrystallization on the crystal size distribution of cloxacillin benzathine crystals, Chem. Eng. Technol. 36(8) (2013) 1341–1346.
[17] Y. Gao, T. Zhang, Y.M. Ma, F.M. Xue, Z.G. Gao, B.H. Hou, J.B. Gong, Application of PAT-based feedback control approaches in pharmaceutical crystallization, Crystals 11(3) (2021) 221.
[18] A.N. Saleemi, C.D. Rielly, Z.K. Nagy, Comparative investigation of supersaturation and automated direct nucleation control of crystal size distributions using ATR-UV/vis spectroscopy and FBRM, Cryst. Growth Des. 12(4) (2012) 1792–1807.
[19] N.C.S. Kee, R.B.H. Tan, R.D. Braatz, Selective crystallization of the metastable aform of l-glutamic acid using concentration feedback control, Cryst. Growth Des. 9(7) (2009) 3044–3051.
[20] J. Yousefi Seyf, A. Haghtalab, Measurement and thermodynamic modeling of the solubility of lamotrigine, deferiprone, cefixime trihydrate, and cephalexin monohydrate in different pure solvents from 283.1 to 323.1 K, J. Chem. Eng. Data 61(6) (2016) 2170–2178.
[21] H. Sun, X.W. Zhang, B.S. Liu, Studies on nucleation kinetics of pyridoxal 5-phosphate monohydrate in water, J. Cryst. Growth 523(2019) 125163.
[22] L. Zhou, Z. Wang, M. Zhang, M. Guo, S. Xu, Q. Yin, Determination of metastable zone and induction time of analgin for cooling crystallization, Chin. J. Chem. Eng. 25(3) (2017) 313–318.
[23] P.F. Liu, Y.F. Zhang, L. Wang, S.W. You, J. Bo, Thermodynamics and nucleation mechanism of ammonium jarosite in sulfuric acid solution, J. Cryst. Growth 478(2017) 52–57.
[24] M. Lenka, D. Sarkar, Determination of metastable zone width, induction period and primary nucleation kinetics for cooling crystallization of lasparaginenohydrate, J. Cryst. Growth 408(2014) 85–90.
[25] K. Renuka Devi, A. Raja, K. Srinivasan, Ultrasound assisted nucleation and growth characteristics of glycine polymorphs: a combined experimental and analytical approach, Ultrason. Sonochem. 24(2015) 107–113.
[26] M. Kurotani, E. Miyasaka, S. Ebihara, I. Hirasawa, Effect of ultrasonic irradiation on the behavior of primary nucleation of amino acids in supersaturated solutions, J. Cryst. Growth 311(9) (2009) 2714–2721.
[27] P. Parimaladevi, K. Srinivasan, Studies on the effect of different operational parameters on the crystallization kinetics of a-lactose monohydrate single crystals in aqueous solution, J. Cryst. Growth 401(2014) 252–259.
[28] Z. Guo, M. Zhang, H. Li, J. Wang, E. Kougoulos, Effect of ultrasound on antisolvent crystallization process, J. Cryst. Growth 273(3-4) (2005) 555–563.
[29] F.X. Hang, T.Q. Qiu, Effect of ultrasound on andrographolide solventing-out crystallization process, J. Chem. Eng. Chin. Univ. 22(4) (2008) 585–590.
[30] Z. Guo, A.G. Jones, N. Li, The effect of ultrasound on the homogeneous nucleation of BaSO₄ during reactive crystallization, Chem. Eng. Sci. 61(5) (2006) 1617–1626.

Ultrasound assisted crystallization of cephalexin monohydrate: Nucleation mechanism and crystal habit control

Ultrasound assisted crystallization of cephalexin monohydrate: Nucleation mechanism and crystal habit control

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