热力学和动力学在三相伴随结晶中的相互作用

摘要伴随多晶型是多种晶型同时析出的特殊现象,在制药过程中需尽力避免。针对磺胺噻唑在水中的三相伴随结晶行为,讨论了热力学和动力学相互作用对其影响。采用动态法测定了磺胺噻唑Form II/III/IV在水中不同温度下的溶解度,表明在15~60 ℃内Form III是热力学稳定晶型,Form II 和 IV具有相似溶解度。测定了不同过饱和度下的成核诱导期和对应多晶型,发现在低过饱和度下(1.15≤S≤1.40),只析出Form III,高过饱和度下(1.90≤S≤9.00)出现三相伴随结晶。动力学测定表明Form IV是动力学最优晶型,但Form II具有最小的临界晶核和成核能垒。动力学和热力学相互作用和竞争解释了上述伴随多晶型的过饱和度依赖关系。引入Ostwald比值预测了磺胺噻唑在水中伴随结晶的三元相图,量化了过饱和度对3种晶型比例的影响。

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	兰金琦
	朱振兴
	谢闯

关键词：伴随多晶型过饱和度结晶热力学成核结晶动力学

Abstract： Concomitant polymorphism is a special phenomenon of simultaneous crystallization of multiple polymorphs, which should be avoided in pharmaceutical process. The effects of thermodynamics-kinetics interaction on the trimorphic concomitant crystallization of sulfathiazole in water were discussed. The solubility of sulfathiazole Form II/III/IV in water at different temperatures was determined using dynamic method, indicating that Form III is a thermodynamically stable polymorph within 15—60 ℃, and Form II & IV have similar solubility. The nucleation induction period and corresponding polymorphs under different supersaturation were determined. It was found that pure Form III can be obtained at low supersaturation (1.15≤S≤1.40), while at high supersaturation (1.90≤S≤9.00) trimorphic concomitant crystallization occurs. Kinetics study shows that Form IV is the kinetically optimal polymorph, but Form II has the smallest critical radius and nucleation energy barriers. The interactions and competition of kinetic and thermodynamics can explain the above-mentioned supersaturation dependence of concomitant polymorphism. The Ostwald ratio was introduced to predict the ternary phase diagram of the concomitant crystallization of sulfathiazole in water, quantifying the effect of supersaturation on the ratio of the three concomitant polymorphs.

Keywords： concomitant polymorphism supersaturation crystallization thermodynamics nucleation crystallization kinetics

Received 2022-04-01;

Fund:中国石油化工股份有限公司石油化工科学研究院开放基金课题(ZC0609-0005)。

Corresponding Authors: 朱振兴,研究员,E-mail:zhuzx.ripp@sinopec.com;谢闯,副研究员,E-mail:acxie@tju.edu.cn。 Email: zhuzx.ripp@sinopec.com;acxie@tju.edu.cn

About author: 兰金琦(1997—),男,硕士研究生,主要从事有机物晶型和形貌调控方向的研究。

引用本文:

兰金琦, 朱振兴, 谢闯.热力学和动力学在三相伴随结晶中的相互作用[J]. 化学工业与工程, 2024,41(6): 149-157

LAN Jinqi, ZHU Zhenxing, XIE Chuang.Interaction between thermodynamics and kinetics in trimorphic concomitant crystallization[J]. Chemcial Industry and Engineering, 2024,41(6): 149-157

[1] BERNSTEIN J. Polymorphism in molecular crystals[M]. Oxford: Oxford University Press, 2007
[2] RAZA K. Polymorphism: The phenomenon affecting the performance of drugs[J]. SOJ Pharmacy & Pharmaceutical Sciences, 2014
[3] NOGUEIRA B A, CASTIGLIONI C, FAUSTO R. Color polymorphism in organic crystals[J]. Communications Chemistry, 2020, 3: 34
[4] FOSTER J A, DAMODARAN K K, MAURIN A, et al. Pharmaceutical polymorph control in a drug-mimetic supramolecular gel[J]. Chemical Science, 2017, 8(1): 78-84
[5] SAIKIA B, MULVEE M T, TORRES-MOYA I, et al. Drug mimetic organogelators for the control of concomitant crystallization of barbital and thalidomide[J]. Crystal Growth & Design, 2020, 20(12): 7989-7996
[6] BLACK J F B, CARDEW P T, CRUZ-CABEZA A J, et al. Crystal nucleation and growth in a polymorphic system: Ostwald’s rule, p-aminobenzoic acid and nucleation transition states[J]. CrystEngComm, 2018, 20(6): 768-776
[7] TEYCHENÉ S, BISCANS B. Nucleation kinetics of polymorphs: Induction period and interfacial energy measurements[J]. Crystal Growth & Design, 2008, 8(4): 1133-1139
[8] BERNSTEIN J, DAVEY R J, HENCK J O. Concomitant polymorphs[J]. Angewandte Chemie (International Ed in English), 1999, 38(23): 3440-3461
[9] MARK ROELANDS C P, JIANG S F, KITAMURA M, et al. Antisolvent crystallization of the polymorphs of l-histidine as a function of supersaturation ratio and of solvent composition[J]. Crystal Growth & Design, 2006, 6(4): 955-963
[10] JIANG S, TER H J H, JANSENS P J. Concomitant polymorphism of o-aminobenzoic acid in antisolvent crystallization[J]. Crystal Growth & Design, 2008, 8(1): 37-43
[11] DU W, YIN Q, BAO Y, et al. Concomitant polymorphism of prasugrel hydrochloride in reactive crystallization[J]. Industrial & Engineering Chemistry Research, 2013, 52(46): 16182-16189
[12] ZHU L, WANG L, SHA Z, et al. Interplay between thermodynamics and kinetics on polymorphic appearance in the solution crystallization of an enantiotropic system, gestodene[J]. Crystal Growth & Design, 2017, 17(9): 4582-4595
[13] TANG W, SIMA A D, GONG J, et al. Kinetic difference between concomitant polymorphism and solvent-mediated phase transformation: A case of tolfenamic acid[J]. Crystal Growth & Design, 2020, 20(3): 1779-1788
[14] WANG G, WANG Y, MA Y, et al. Concomitant crystallization of cefuroxime acid and its acetonitrile solvate in acetonitrile and water solution[J]. Industrial & Engineering Chemistry Research, 2014, 53(36): 14028-14035
[15] JIA L, YIN Q, ZHOU L, et al. Insights into the mechanism of concomitant nucleation of form II and ethanol solvate of spironolactone in cooling crystallization[J]. RSC Advances, 2018, 8(18): 9697-9706
[16] OSTWALD W. Studien über die Bildung und Umwandlung fester Körper[J]. Zeitschrift Für Physikalische Chemie, 1897, 22U(1): 289-330
[17] CARDEW P, DAVEY R J. The Ostwald ratio, kinetic phase diagrams, and polymorph maps[J]. Crystal Growth & Design, 2019, 19(10): 5798-5810
[18] SONG S, WANG L, YAO C, et al. Crystallization of sulfathiazole in gel: Polymorph selectivity and cross-nucleation[J]. Crystal Growth & Design, 2020, 20(1): 9-16
[19] YU J, YAN J, JIANG L. Crystallization of polymorphic sulfathiazole controlled by femtosecond laser-induced cavitation bubbles[J]. Crystal Growth & Design, 2021, 21(6): 3202-3210
[20] BORA P, SAIKIA B, SARMA B. Oriented crystallization on organic monolayers to control concomitant polymorphism[J]. Chemistry, 2020, 26(3): 699-710
[21] LI W, IKNI A, SCOUFLAIRE P, et al. Non-photochemical laser-induced nucleation of sulfathiazole in a water/ethanol mixture[J]. Crystal Growth & Design, 2016, 16(5): 2514-2526
[22] ABU BAKAR M R, NAGY Z K, RIELLY C D, et al. Investigation of the riddle of sulfathiazole polymorphism[J]. International Journal of Pharmaceutics, 2011, 414(1/2): 86-103
[23] MUNROE Á, RASMUSON Å C, HODNETT B K, et al. Relative stabilities of the five polymorphs of sulfathiazole[J]. Crystal Growth & Design, 2012, 12(6): 2825-2835
[24] MUNROE A, CROKER D, RASMUSON Å C, et al. Analysis of FII crystals of sulfathiazole: Epitaxial growth of FII on FIV[J]. CrystEngComm, 2011, 13(3): 831-834
[25] LEE I S, LEE A Y, MYERSON A S. Concomitant polymorphism in confined environment[J]. Pharmaceutical Research, 2008, 25(4): 960-968
[26] TAKEBAYASHI Y, SUE K, FURUYA T, et al. Polymorphic solubility ratio of famotidine and sulfathiazole in various solvents[J]. Crystal Growth & Design, 2021, 21(5): 2868-2875
[27] KARTHIKA S, RADHAKRISHNAN T K, KALAICHELVI P. A review of classical and nonclassical nucleation theories[J]. Crystal Growth & Design, 2016, 16(11): 6663-6681
[28] FRENKEL J. A general theory of heterophase fluctuations and pretransition phenomena[J]. The Journal of Chemical Physics, 1939, 7(7): 538-547
[29] KASHCHIEV D, VAN ROSMALEN G M. Review: Nucleation in solutions revisited[J]. Crystal Research and Technology, 2003, 38(7/8): 555-574
[30] VEKILOV P G. Nucleation[J]. Crystal Growth & Design, 2010, 10(12): 5007-5019
[31] LIU J, SVÄRD M, RASMUSON Å C. Influence of Agitation and Fluid Shear on Nucleation of m-Hydroxybenzoic Acid Polymorphs[J]. Crystal Growth & Design, 2014, 14(11): 5521-5531
[32] LENKA M, SARKAR D. Determination of metastable zone width, induction period and primary nucleation kinetics for cooling crystallization of l-asparaginenohydrate[J]. Journal of Crystal Growth, 2014, 408: 85-90
[33] DAVEY R J, SCHROEDER S L M, TER HORST J H. Nucleation of organic crystals: A molecular perspective[J]. Angewandte Chemie (International Ed in English), 2013, 52(8): 2166-2179
[34] SHTUKENBERG A G, HU L, SAHOTA A, et al. Disrupting crystal growth through molecular recognition: Designer therapies for kidney stone prevention[J]. Accounts of Chemical Research, 2022, 55(4): 516-525