硫酸氢氯吡格雷球形结晶工艺及其生长机理

doi:10.11949/j.issn.0438-1157.20151084

化工学报 ›› 2015, Vol. 66 ›› Issue (9): 3633-3639.DOI: 10.11949/j.issn.0438-1157.20151084

硫酸氢氯吡格雷球形结晶工艺及其生长机理

王海洋^1,2, 杜艳妮^1,2, 李振方^1,2, 宋晓鹏^1,2, 谭端明³, 龚俊波^1,2

1 天津大学化工学院化学工程联合国家重点实验室, 天津 300072;
2 天津化学化工协同创新中心, 天津 300072;
3 深圳信立泰药业股份有限公司, 深圳 518102

收稿日期:2015-07-07 修回日期:2015-07-18 出版日期:2015-09-05 发布日期:2015-09-05
通讯作者: 龚俊波
基金资助:
国家自然科学基金项目(21376174)。

Crystallization process and growth mechanism for spherical products of clopidogrel sulfate

WANG Haiyang^1,2, DU Yanni^1,2, LI Zhenfang^1,2, SONG Xiaopeng^1,2, TAN Duanming³, GONG Junbo^1,2

1 School of Chemical Engineering, State Key Laboratory of Chemical Engineering, Tianjin University, Tianjin 300072, China;
2 Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300072, China;
3 Salubris Pharmaceutical Co., Ltd., Shenzhen 518102, China

Received:2015-07-07 Revised:2015-07-18 Online:2015-09-05 Published:2015-09-05
Supported by:
supported by the National Natural Science Foundation of China (21376174).

摘要/Abstract

摘要：

本文测定了硫酸氢氯吡格雷Ⅰ、Ⅱ晶型在仲丁醇中的溶解度,通过过程分析和优化,制备了纯Ⅰ晶型的硫酸氢氯吡格雷球形晶体。与非球形晶体比较,球形晶体在堆密度、流动性、粒度分布以及稳定性等方面均占优势。本文考察了不同温度、残留溶剂对硫酸氢氯吡格雷晶习与晶型的影响,研究了硫酸氢氯吡格雷球形结晶过程晶体的生长机理。

关键词: 硫酸氢氯吡格雷, 多晶型, 球形结晶, 生长机理

Abstract:

The difference between solubility of clopidogrel sulfate form Ⅰ and form Ⅱ in 2-butanol was determined by dynamic method. Based on process analysis and optimization of clopidogrel sulfate crystallization in solutions, clopidogrel sulfate of form Ⅰ was acquired with spherical shape. Compared with the non-spherical products, the spherical one possesses advantages in bulk density, flow ability, size distribution and stability. The crystal habit and crystal form of products prepared at different temperatures and residual solvents were investigated, the kinetics and growth mechanism of the spherical crystallization process was studied.

Key words: clopidogrel sulfate, polymorphism, spherical crystallization, growth mechanism

中图分类号:

TQ463⁺.54

王海洋, 杜艳妮, 李振方, 宋晓鹏, 谭端明, 龚俊波. 硫酸氢氯吡格雷球形结晶工艺及其生长机理[J]. 化工学报, 2015, 66(9): 3633-3639.

WANG Haiyang, DU Yanni, LI Zhenfang, SONG Xiaopeng, TAN Duanming, GONG Junbo. Crystallization process and growth mechanism for spherical products of clopidogrel sulfate[J]. CIESC Journal, 2015, 66(9): 3633-3639.

参考文献 24

[1]	Mangin D, Puel F, Veesler S. Polymorphism in processes of crystallization in solution: a practical review [J]. Organic Process Research & Development, 2009, 13 (6): 1241-1253.
[2]	Sharma P, Zujovic Z D, Bowmaker G A, Denny W A, Garg S. Evaluation of a crystalline nanosuspension: polymorphism, process induced transformation and in vivo studies [J]. International Journal of Pharmaceutics, 2011, 408 (1): 138-151.
[3]	Jiang Shanfeng, Jansens P J, ter Horst J H. Control over polymorph formation of o-aminobenzoic acid [J]. Crystal Growth & Design, 2010, 10 (6): 2541-2547.
[4]	Martínez-Ohárriz M C, Martin C, Goni M M, Rodríguez- Espinosa C, Ilarduya-Apaolaza D, Tros M C, Sánchez M. Polymorphism of diflunisal: isolation and solid-state characteristics of a new crystal form [J]. Journal of Pharmaceutical Sciences, 1994, 83 (2): 174-177.
[5]	Kralj D, Bre?evi? L, Nielsen A E. Vaterite growth and dissolution in aqueous solution (Ⅰ): Kinetics of crystal growth [J]. Journal of Crystal Growth, 1990, 104 (4): 793- 800.
[6]	Jiang Shanfeng, Jansens P J, ter Horst J H. Mechanism and kinetics of the polymorphic transformation of o- aminobenzoic acid [J]. Crystal Growth & Design, 2010, 10 (5): 2123-2128.
[7]	Nath N K, Aggarwal H, Nangia A. Crystal structure of methyl paraben polymorph Ⅱ [J]. Crystal Growth & Design, 2011, 11 (4): 967-971.
[8]	Roy S, Bhatt P M, Nangia A, Kruger G J. Stable polymorph of venlafaxine hydrochloride by solid-to-solid phase transition at high temperature [J]. Crystal Growth & Design, 2007, 7 (3): 476-480.
[9]	Mo Yuxin, Dang Leping, Wei Hongyuan. L-Glutamic acid polymorph control using amino acid additives [J]. Industrial & Engineering Chemistry Research, 2011, 50 (18): 10385-10392.
[10]	Price C P, Grzesiak A L, Matzger A J. Crystalline polymorph selection and discovery with polymer heteronuclei [J]. Journal of the American Chemical Society, 2005, 127 (15): 5512-5517.
[11]	McKellar S C, Urquhart A J, Lamprou D A, Florence A J. Polymer templating of supercooled indomethacin for polymorph selection [J]. ACS Combinatorial Science, 2012, 14 (3): 155-159.
[12]	Croker D, Hodnett B K. Mechanistic features of polymorphic transformations: the role of surfaces [J]. Crystal Growth & Design, 2010, 10 (6): 2806-2816.
[13]	Doki N, Seki H, Takano K, Asatani H, Yokota M, Kubota N. Process control of seeded batch cooling crystallization of the metastable α-form glycine using an in-situ ATR- FTIR spectrometer and an in-situ FBRM particle counter [J]. Crystal Growth & Design, 2004, 4 (5): 949-953.
[14]	Hausman D S, Cambron R T, Sakr A. Application of on-line Raman spectroscopy for characterizing relationships between drug hydration state and tablet physical stability [J]. International Journal of Pharmaceutics, 2005, 299 (1): 19-33.
[15]	Braun D E, Karamertzanis P G, Arlin J B, Florence A J, Kahlenberg V, Tocher D A, Price S L. Solid-state forms of β-resorcylic acid: how exhaustive should a polymorph screen be? [J]. Crystal Growth & Design, 2010, 11 (1): 210-220.
[16]	Kawashima Y, Okumura M, Takenaka H. Spherical crystallization: direct spherical agglomeration of salicylic acid crystals during crystallization [J]. Science, 1982, 216 (4550): 1127-1128.
[17]	Zhang Haitao, Chen Ying, Wang Jingkang, Gong Junbo. Investigation on the spherical crystallization process of cefotaxime sodium [J]. Industrial & Engineering Chemistry Research, 2009, 49 (3): 1402-1411.
[18]	Kawashima Y, Aoki S, Takenaka H, Miyake Y. Preparation of spherically agglomerated crystals of aminophylline [J]. Journal of Pharmaceutical Sciences, 1984, 73 (10): 1407-1410.
[19]	Kawashima Y, Niwa T, Handa T, Takeuchi H, Iwamoto T, Itoh K. Preparation of controlled-release microspheres of ibuprofen with acrylic polymers by a novel quasi-emulsion solvent diffusion method [J]. Journal of Pharmaceutical Sciences, 1989, 78 (1): 68-72.
[20]	Nocent M, Bertocchi L, Espitalier F, Baron M, Couarraze G. Definition of a solvent system for spherical crystallization of salbutamol sulfate by quasi-emulsion solvent diffusion (QESD) method [J]. Journal of Pharmaceutical Sciences, 2001, 90 (10): 1620-1627.
[21]	Ueda M, Nakamura M Y, Makita H, Imasato Y, Kawashima Y. Particle design of enoxacin by spherical crystallization technique [J]. Chem. Pharm. Bull., 1990, 38 (9): 2537-2541.
[22]	Puechagut H G, Bianchotti J, Chiale C A. Preparation of norfloxacin spherical agglomerates using the ammonia diffusion system [J]. Journal of Pharmaceutical Sciences, 1998, 87 (4): 519-523.
[23]	Pawar A P, Paradkar A R, Kadam S S, Mahadik K R. Crystallo-co-agglomeration: a novel technique to obtain ibuprofen- paracetamol agglomerates [J]. AAPS Pharm. Sci. Tech., 2004, 5 (3): 57-64.
[24]	Kawashima Y, Handa T, Takeuchi H. Crystal modification of phenytoin with polyethylene glycol for improving mechanical strength, dissolution rate and bioavailability by a spherical crystallization technique [J]. Chemical & Pharmaceutical Bulletin, 1986, 34 (8): 3376-3383.

硫酸氢氯吡格雷球形结晶工艺及其生长机理

Crystallization process and growth mechanism for spherical products of clopidogrel sulfate

PDF (PC)

可视化

被引次数

摘要/Abstract

引用本文

使用本文

参考文献 24

相关文章 11

编辑推荐

Metrics

本文评价

[1]	林家伟, 石鹏, 龚俊波, 吴送姑. 表面诱导药物多晶型成核的研究进展[J]. 化工学报, 2021, 72(2): 814-827.
[2]	李国华, 孙海标, 喻洋, 谢伟淼. 火柴棒状纳米碳管的制备及其生长机理[J]. 化工学报, 2015, 66(9): 3801-3807.
[3]	崔贤羡, 管卉, 黄民. 高结晶度ZSM-5分子筛合成及分子动力学模拟[J]. 化工学报, 2013, 64(4): 1493-1498.
[4]	杨倩鹏, 陈晓东, 田磊, 史琳. 不同营养下混合菌种微生物污垢生长机理与交互作用[J]. 化工学报, 2013, 64(3): 1036-1041.
[5]	龚俊波, 王琦, 董伟兵, 王静康. 药物晶型转化与控制的研究进展[J]. 化工学报, 2013, 64(2): 385-392.
[6]	王晓东, 张宝泉, 刘秀凤. 取向TS-1分子筛膜的合成与结构引导机理 [J]. 化工学报, 2007, 58(9): 2408-2411.
[7]	郎林;张宝泉;刘秀凤 . 在玻璃上合成有取向的silicalite-1分子筛膜及其生长机理 [J]. CIESC Journal, 2006, 57(9): 2229-2232.
[8]	卢咏琰;刘海岛;尹秋响 . 对叔辛基酚的多晶特性 [J]. CIESC Journal, 2006, 57(9): 2233-2236.
[9]	刘秀凤;郎林;张宝泉;Y.S.LIN. 在壳聚糖改性的硅锆复合中间层上原位水热合成b-轴取向silicalite-1分子筛膜 [J]. CIESC Journal, 2006, 57(4): 1019-1022.
[10]	蒋海洋, 张宝泉, 林跃生, 李永丹. 无模板剂二次生长法合成MFI分子筛膜的生长机理 [J]. 化工学报, 2005, 56(6): 1141-1143.
[11]	赖琛, 唐绍裘, 王迎军, 魏小焜, 张世英. 微乳法合成磷酸钙纳米纤维及其机理探讨 [J]. 化工学报, 2005, 56(5): 942-946.