Objective  To analyze the crystal forms of albendazole raw materials obtained by recrystallization from different solvents, and to explore the dissolution properties of different crystal forms of albendazole raw materials and their tablets.

Methods  Commercial albendazole was recrystallized from methanol and chloroform to obtain two crystal forms, which were characterized by differential scanning calorimetry, field emission scanning electron, and X-ray powder diffraction. Performance study on the dissolution rate of different crystal forms of raw materials and their corresponding tablets was conducted using a flow cell dissolution apparatus and a dissolution medium of 0.1 mol/L hydrochloric acid solution.

Results  The raw materials of albendazole obtained by recrystallization from two different solvents corresponded to different crystal forms, and there were significant differences in dissolution rate between these two crystal forms and their mixed crystal forms. On this basis, tablets prepared from different crystal types of raw materials also exhibited significant differences in dissolution properties.

Conclusion  The crystal form of albendazole may be a key influencing factor for its in vitro dissolution. This study provides experimental evidence for the quality consistency evaluation of albendazole preparations, and also lays a scientific foundation for ensuring their clinical efficacy.

1.薛晶, 许鸣镝, 南楠, 等. 原辅料及制剂处方工艺对口服固体制剂溶出行为的影响[J]. 中国新药杂志, 2017, 26(12): 1370-1375. [Xue J, Xu MD, Nan N, et al. Effects of APIs, excipients, formulations and technologies on the dissolution profiles of solid oral preparations[J]. Chinese Journal of New Drugs, 2017, 26(12): 1370-1375.] DOI: CNKI:SUN:ZXYZ.0.2017-12-004.

2.陆成晖, 陈智林, 孙兴华, 等. 浅谈新药研发中的晶型研究 [J]. 中国药师, 2022, 25(7): 1245-1248. [Lu CH, Chen ZL, Sun XH, et al. Brief discussion on crystal form in new drug research and development[J]. China Pharmacist, 2022, 25(7): 1245-1248.] DOI: 10.19962/j.cnki.issn1008-049X.2022.07.026.

3.吴蔚, 朱荣. 重视对药物晶型的研究[J]. 中国药业, 2004, 13(11): 18-20. [Wu W, Zhu R. Importance of studying the crystal forms of drugs[J]. China Pharmaceuticals, 2004, 13(11): 18-20.] DOI: 10.3969/j.issn.1006-4931.2004.11.022.

4.王蕾, 刘德胜, 潘宁, 等. 药物多晶型与固体制剂的关系研究进展[J]. 实用药物与临床, 2001, 4(1): 35-37. [Wang L, Liu  DS, Pan N, et al. Research progress on the relationship between drug polymorphs and solid formulations[J]. Practical Pharmacy and Clinical Remedies, 2001, 4(1): 35-37.] DOI: 10.3969/j.issn.1673-0070.2001.01.023.

5.吕宝茹, 于鑫, 李宁, 等. 不同厂家生产罗红霉素原料药的表征及其片剂制剂溶出的比较研究[J]. 药物分析杂, 2019, 39(4): 735-743. [Lyu BR, Yu X, Li N, et al. Characterizations of roxithromycin APIS from different manufacturers and studies of the dissolution profiles of their tablets[J]. Chinese Journal of Pharmaceutical Analysis, 2019, 39(4): 735-743.] DOI: 10.16155/j.0254-1793.2019.04.21.

6.曾凡彬. 影响难溶性药物口服固体制剂溶出特性的理化因素--晶型和粒度[J]. 中国新药杂志, 2002, 11(7): 507-509. [Zeng FB. Physical and chemical factors affecting the dissolution characteristics of poorly soluble drugs in oral solid formulations-crystal form and particle size[J]. Chinese Journal of New Drugs, 2002, 11(7): 507-509.] DOI: 10.3321/j.issn:1003-3734.2002.07.002.

7.王健, 曾红霞, 陈悦. 罗红霉素晶型分析及与溶解速率、溶出度的关系[J]. 中国现代应用药学, 2013, 30(10): 1094-1097. [Wang J, Zeng HX, Chen Y, et al. Relationship of roxithromycin crystal types, dissolution rates and dissolution[J]. Chinese Journal of Modern Applied Pharmacy, 2013, 30(10): 1094-1097.] DOI: 10.13748/j.cnki.issn1007-7693.2013.10.021.

8.陈华, 赵文, 毛睿, 等. 2种晶型利福平制剂之间溶出曲线的差异[J]. 药物分析杂志, 2013, 33(5): 881-884, 893. [Chen H, Zhao W, Mao R, et al. Differences of dissolution profiles between two crystallines types of fixed dose combinations of rifampin[J]. Chinese Journal of Pharmaceutical Analysis, 2013, 33(5): 881-884, 893.] DOI: CNKI:SUN:YWFX.0.2013-05-033.

9.夏颖帆, 蒋成君. 新晶型替格瑞洛的制备、表征及溶解性能研究[J].药物分析杂志2023, 40(8): 1086-1090. [Xia  YF, Jiang  CJ. Preparation, characterization and improved solubility of new crystal form of ticagrelor[J]. Chinese Journal of Pharmaceutical Analysis, 2023, 40(8): 1086-1090.] DOI: 10.13748/j.cnki.issn1007-7693.20220776.

10.陈格, 余琼娥. 不同晶型阿莫西林原料对制剂溶出行为的影响[J]. 中外医学研究, 2013, 11(13): 136-137. [Chen  G, Yu QE. Effect of different crystal type of amoxicillin raw material on the stripping behavior of preparation[J]. Chinese and Foreign Medical Research, 2013, 11(13): 136-137.] DOI: CNKI:SUN:YJZY.0.2013-13-099.

11.郑爱华, 黄金占, 陈祖国. 合成阿苯达唑的研究进展[J]. 浙江化工, 2018, 49(12): 1-5, 9. [Zheng AH, Huang JZ, Chen ZG, et al. Research progress in synthesis of albendazole[J]. Zhejiang Chemical Industry, 2018, 49(12): 1-5, 9.] DOI: 10.3969/j.issn. 1006-4184.2018.12.001.

12.Palomares-Alonso F, Toledo A, Hernández GP, et al. Effect of dexamethasone on albendazole cysticidal activity in experimental cysticercosis by Taenia crassiceps in BALA/c mice: in vitro and in vivo[J]. Exp Parasitol, 2020, 208: 107801. DOI: 10.1016/j.exppara.2019.107801.

13.Guo C, Fritz MP, Struppe J, et al. NMR crystallography at fast magic-angle spinning frequencies[J]. Anal Chem, 2021, 93(23): 8210-8218. DOI: 10.1021/acs.analchem.1c00784.

14.Pettarin M, Bolger MB, Chronowska M, et al. A combined in vitro in-silico approach to predict the oral bioavailability of borderline BCS Class II/IV weak base albendazole and its main metabolite albendazole sulfoxide[J]. Eur J Pharm Sci, 2020, 155: 105552. DOI: 10.1016/j.ejps.2020.105552.

15.马玲, 王曼泽, 朱捷, 等. 阿苯达唑片多条溶出曲线的研究和测定[J]. 中国药学杂志, 2018, 3(24): 2123-2126. [Ma L, Wang MZ, Zhu J, et al. Determination of the dissolution curves of albendazole tablets[J]. Chinese Pharmaceutical Journal, 2018, 3(24): 2123-2126.] DOI: 10.11669/cpj.2018.24.011.

16.谢莉, 陈红, 张亿.流通池法测定甲硝唑口腔粘贴片的释放度 [J]. 中国药师, 2020, 23(4): 761-764. [Xie L, Chen  H, Zhang  Y, et al. Dissolution determination of metronidazole oral sticking tablets by flow-through cell method[J]. China Pharmacist, 2020, 23(4): 761-764.] DOI: 10.3969/j.issn.1008-049X.2020.04.041.

17.中国药典2025年版. 二部[S]. 2025: 722.