药学学报, 2021, 56(11): 3166-3172
引用本文:
朱恒清, 高晓芳, 郑道一, 孟文卉, 庞遵霆, 高缘. 晶型及填充剂对克拉霉素压缩成型性的影响[J]. 药学学报, 2021, 56(11): 3166-3172.
ZHU Heng-qing, GAO Xiao-fang, ZHENG Dao-yi, MENG Wen-hui, PANG Zun-ting, GAO Yuan. Effect of crystal form and filler on the compressibility of clarithromycin[J]. Acta Pharmaceutica Sinica, 2021, 56(11): 3166-3172.

晶型及填充剂对克拉霉素压缩成型性的影响
朱恒清1, 高晓芳2, 郑道一2, 孟文卉2, 庞遵霆1, 高缘1*
1. 中国药科大学中药学院, 江苏 南京 211198;
2. 中国药科大学药学院, 江苏 南京 211198
摘要:
克拉霉素是第二代大环内酯类抗生素。市售克拉霉素原料药为稳定晶型 (晶型II),其在压片过程存在压缩成型性差的问题。由于堆积方式不同,不同晶型的机械性质可能存在较大的差异性,本研究一方面从多晶型角度研究了克拉霉素晶型I (亚稳晶型) 与晶型II压缩成型性的差异及产生差异的机制;另一方面从制剂学角度考察了常用填充剂对晶型II压缩成型性的影响。结果表明,由于晶型I晶体结构中存在滑移面,可增加颗粒塑性形变,从而表现出显著优于晶型II的压缩成型性;微晶纤维素、预胶化淀粉和乳糖一水合物均可提高晶型II压缩成型性,其中微晶纤维素改善效果最优。从晶型及填充剂两个角度提高克拉霉素可压性,为克拉霉素的固体制剂开发奠定基础。
关键词:    克拉霉素      压缩成型性      晶型      滑移面      填充剂     
Effect of crystal form and filler on the compressibility of clarithromycin
ZHU Heng-qing1, GAO Xiao-fang2, ZHENG Dao-yi2, MENG Wen-hui2, PANG Zun-ting1, GAO Yuan1*
1. School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, China;
2. School of Pharmacy, China Pharmaceutical University, Nanjing 211198, China
Abstract:
Clarithromycin (CLA) belongs to the second generation macrolide antibiotic. The commercial crystal form of CLA is form II, and it exhibits the poor compressibility during the tablet pressing process. Since the crystal form of drugs has a significant effect on their mechanical properties, from the perspective of crystallography, this study investigated the difference of the compressibility between CLA form I and form II, and analyzed the mechanism that led to such difference. On the other hand, from the perspective of pharmaceutics, we also studied the effect of filler on the compressibility of form II. It was found that CLA form I had improved plastic deformation than form II because of the slip planes in its crystal structure leading to the better compressibility. Moreover, microcrystalline cellulose, pre-gelatinized starch and lactose monohydrate could improve the compressibility of form II, and microcrystalline cellulose showed the best effect. We improve the compressibility of CLA from crystal form and filler, and also lay a foundation for the development of CLA solid preparations.
Key words:    clarithromycin    compressibility    polymorphism    slip plane    filler   
收稿日期: 2021-04-22
DOI: 10.16438/j.0513-4870.2021-0600
基金项目: 国家自然科学基金资助项目(81773675,81873012,82074029);中国药科大学“双一流”建设(CPU2018GY11,CPU2018GY27);大学生创新创业训练计划项目(202110316034).
通讯作者: 高缘,Tel/Fax:86-25-83379418,E-mail:newgaoyuan@163.com
Email: newgaoyuan@163.com
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