Ingredient Analysis

Study on thermal properties of ticagrelor form Ⅱ based on thermal analysis technology

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  • 1. Zhejiang Jingxin Pharmaceutical Co., Ltd., Xinchang 312500, China;
    2. Chemistry Department, Zhejiang University, Hangzhou 310028, China

Received date: 2022-10-25

  Online published: 2024-06-24

Abstract

Objective: To study the thermal properties of ticagrelor form Ⅱ. Methods: Thermal properties of ticagrelor form Ⅱ was analyzed by differential scanning calorimetry and hot stage microscopy. Combined with powder X-ray diffraction and optical microscopy, the relationship between the crystal form, crystal habit and thermal properties of ticagrelor form Ⅱ was analyzed. Results: Ticagrelor form Ⅱ had needle-like crystal habit with different aspect ratios, which were manifested as the changes of relative intensities of characteristic peaks on the powder X-ray diffraction pattern. There was a melting transition phenomenon of ticagrelor form Ⅱ in the heating process. Crystal habit, particle size, as well as the heating rate of differential scanning calorimeter had a great influence on the degree of melting transition phenomenon. The double peaks in DSC spectrum could be caused by polymorphic transformation rather than mixed polymorphic crystal when PXRD and other characterization results showed that it was pure ticagrelor form Ⅱ. Conclusion: Through the study of the thermal properties of ticagrelor form Ⅱ, it provides a reasonable explanation for the phenomenon that some DSC patterns of the same drug substance with the same crystal form showed double peaks and some showed single peaks. This study provides more information for the quality control of ticagrelor.

Cite this article

ZHOU Xin-bo, JIN Zhi-ping, REN Yan, CHEN Lin-shen, ZHU Zhan-gen, HU Xiu-rong . Study on thermal properties of ticagrelor form Ⅱ based on thermal analysis technology[J]. Chinese Journal of Pharmaceutical Analysis, 2023 , 43(9) : 1461 -1467 . DOI: 10.16155/j.0254-1793.2023.09.02

References

[1] 赵凯凯, 白俊琴, 张波. 新型P2Y12受体拮抗剂替格瑞洛广谱抗血小板作用机制的研究进展[J]. 中国动脉硬化杂志, 2022, 30(2):180
ZHAO KK, BAI JQ, ZHANG B. Research progress on the mechanisim of broad-spectrum antiplatelet effect of novel P2Y12 receptor antagonist ticagrelor [J]. Chin J Arterioscler, 2022, 30(2):180
[2] DEEKS ED. Ticagrelor [J]. Drugs, 2011, 71(7):909
[3] DOBESH PP, OESTREICH JH. Ticagrelor: pharmacokinetics, pharmacodynamics, clinical efficacy, and safety[J]. Pharmacotherapy,2014,34(10):1077
[4] HUSTED S, GIEZEN JJJV. Ticagrelor: the first reversibly binding oral P2Y12 receptor antagonist[J]. Cardiovasc Ther, 2009, 27(4):259
[5] BOHLIN M, COSGROVE S, LASSEN B. Crystalline and Amorphous form of Triazolo (4,5-d) Pyrimidine Compound: US, 7265124[P]. 2007-09-04
[6] 胡秀荣, 吴佳佳, 沈金, 等. 替格瑞洛的一水合物及其制备方法与在制药中的应用: 中国, 104341423[P]. 2015-02-11
HU XR, WU JJ, SHEN J, et al. Ticagrelor Monohydrate, Preparation Method Thereof and Pharmaceutical Application Thereof: China, 104341423[P]. 2015-02-11
[7] 胡晨阳, 任芳俊, 盛晓霞, 等. 替卡格雷晶型及其制备方法和用途: 中国, 104098570[P].2014-10-15
HU CY, REN FJ, SHENG XX, et al. Crystal form of Ticagrelor Brilinta and Preparation Method and Purpose Thereof: China, 104098570[P].2014-10-15
[8] 袁建栋, 陈敏华. 替卡格雷晶型及其制备方法:中国, 103772393 [P]. 2014-05-07
YUAN JD, CHEN MH. Ticagrelor Crystal Forms and Preparation Method Thereof: China, 103772393 [P]. 2014-05-07
[9] 周付刚, 张雅然, 马玉秀, 等. 一种替卡格雷新结晶及其制备方法: 中国, 104710425[P]. 2015-06-17
ZHOU FG, ZHANG YR, MA YX, et al. Ticagrelor New Crystal and Preparation Method Thereof: China, 104710425[P]. 2015-06-17
[10] 郭璠, 黄文武, 郑少军, 等. 替格瑞洛的新结晶形式及其制备方法和用途: 中国, 105418614[P]. 2016-03-23
GUO F, HUANG WW, ZHENG SJ, at al. New Crystal Form of Ticagrelor as well as Preparation Method and Application Thereof: China, 105418614[P]. 2016-03-23
[11] 尚德斌, 姜维平, 贾春荣. 一种替格瑞洛新晶型S及其在药物制剂中的应用: 中国, 108203436[P].2018-06-26
SHANG DB, JIANG WP, JIA CR. Novel Crystal form S of Ticagrelor, and Application of Same to Medicinal Preparations: China, 108203436[P]. 2018-06-26
[12] 季伟杰.替格瑞洛的多晶型行为研究[D].杭州: 浙江工业大学, 2016
JI WJ. The Study of Ticagrelor Polymorphism Behaviors [D].Hangzhou: Zhejiang University of Technology, 2016
[13] 喻红梅, 房政钰, 邢逞, 等. 替格瑞洛新盐型的制备、表征及溶解性能研究[J]. 药学学报, 2021, 56(2):570
YU HM, FANG ZY, XING C, et al. Preparation, characterization and improved solubility of ticagrelor salts[J]. Acta Pharm Sin, 2021, 56(2):570
[14] INAM M, WU JJ, SHEN J, et al. Preparation and characterization of novel pharmaceutical co-crystals: ticagrelor with nicotinamide[J]. Crystals,2018, 8:336
[15] YANG S, WU Y, ZHANG H, et al. Solubility measurement of crystal form Ⅱ and form V ticagrelor in several pure organic solvents[J]. J Chem Eng Data, 2021,66:2022
[16] 申建伟, 赵金红, 吴晶, 等. 替格瑞洛晶型热力学稳定性关系研究[J]. 中国处方药, 2022,20(3):33
SHEN JW, ZHAO JH, WU J, et al. Study on thermodynamic stability relationship of ticagrelor polymorph[J]. J China Prescripn Drug, 2022,20(3):33
[17] REN Y, SHEN J, YU K, et al. Impact of crystal habit on solubility of ticagrelor[J]. Crystals, 2019, 9:556
[18] BOJARSKA J, REMKO M, FRUZIѝSKI A, et al. The experimental and theoretical landscape of a new antiplatelet drug ticagrelor: Insight into supramolecular architecture directed by CH…F, π…π and CH…π interactions[J]. J Mol Struct, 2018, 1154: 290
[19] HARTMAN P, PERDOK WG. On the relations between structure and morphology of crystals I [J]. Acta Crystallograph, 1955, 8(1):49
[20] INOUE M, HIRASAWA I. The relationship between crystal morphology and XRD peak intensity on CaSO4·2H2O[J]. J Cryst Growth, 2013,380:169
[21] 朱炯, 吴建敏, 黄海伟, 等. 差示扫描量热法在药品检验中的研究进展[J]. 中国药事, 2018, 32(2):210
ZHU J, WU JM, HUANG HW, et al. Research progress of differential scanning calorimetry in drug testing[J]. Chin Pharm Aff, 2018, 32(2):210
[22] BARBAS R, MARTÍ F, PROHENS R, et al. Polymorphism of norfloxacin: Evidence of the enantiotropic relationship between polymorphs A and B[J]. Cryst Growth Des, 2006, 6: 1463
[23] ZENCIRCI N, GELBRICH T, APPERLEY DC, et al. Structural features, phase relationships and transformation behavior of the polymorphs Ⅰ-Ⅵ of phenobarbital[J]. Cryst Growth Des, 2010, 10: 302
[24] BORCHERT C, TEMMEL E, EISENSCHMIDT H, et al. Image-based in situ identification of face specific crystal growth rates from crystal populations[J]. Cryst Growth Des, 2014, 14(3):952
[25] CHOW K, TONG HHY, LUM S, et al. Engineering of pharmaceutical materials: an industrial perspective[J]. J Pharm Sci, 2008, 97(8):2855
[26] RAMAMOORTHY S, KWAK JH, KARANDE P, et al. A high-throughput assay for screening modifiers of calcium oxalate crystallization[J]. AIChE J, 2016, 62(10):3538
[27] KLAPWIJK AR, SIMONE E, NAGY ZK, et al. Tuning crystal morphology of succinic acid using a polymer additive[J]. Cryst Growth Des, 2016, 16(8):4349
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