药学学报, 2021, 56(5): 1460-1469
引用本文:
王增明, 李先福, 韩晓璐, 柳爱爱, 洪晓轩, 李聪慧, 郑爱萍*. 全因子实验设计在黏结剂喷射型3D打印制剂打印液开发中的应用[J]. 药学学报, 2021, 56(5): 1460-1469.
WANG Zeng-ming, LI Xian-fu, HAN Xiao-lu, LIU Ai-ai, HONG Xiao-xuan, LI Cong-hui, ZHENG Ai-ping*. Full-factor design of experiment application in the development of printing ink for binder jetting 3D printed preparation[J]. Acta Pharmaceutica Sinica, 2021, 56(5): 1460-1469.

全因子实验设计在黏结剂喷射型3D打印制剂打印液开发中的应用
王增明, 李先福, 韩晓璐, 柳爱爱, 洪晓轩, 李聪慧, 郑爱萍*
军事科学院军事医学研究院毒物药物研究所, 北京 100850
摘要:
打印液开发是黏结剂喷射型3D打印制剂的重点和难点,直接决定了打印产品的质量。本研究运用质量源于设计理念,采用3个中心点的23全因子实验设计(Design of Experiment,DoE),对左乙拉西坦3D打印分散片的打印液组成进行优化。使用40%(v/v)异丙醇水溶液作为基础溶剂,以聚乙烯吡咯烷酮K30、甘油及聚山梨酯20用量作为自变量,分析其对打印片剂重量差异、硬度、脆碎度及分散均匀性等关键质量属性的影响。通过DoE模型分析获得了打印液处方的设计空间,并通过响应优化器获得了最优的打印液处方:含有0.1%(w/w)聚乙烯吡咯烷酮K30和4.0%(w/w)甘油的异丙醇水溶液。对打印液的喷射机制和润湿性进行分析,并制备和表征了不同规格的3D打印个性化制剂,验证了打印液处方的合理性,为黏结剂喷射型3D打印制剂中打印液的研究提供了参考和依据。
关键词:    黏结剂喷射技术      3D打印      左乙拉西坦分散片      打印液      设计空间      喷射机制     
Full-factor design of experiment application in the development of printing ink for binder jetting 3D printed preparation
WANG Zeng-ming, LI Xian-fu, HAN Xiao-lu, LIU Ai-ai, HONG Xiao-xuan, LI Cong-hui, ZHENG Ai-ping*
Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Academy of Military Sciences, Beijing 100850, China
Abstract:
The development of printing ink is a challenge for binder jetting 3D printed preparations, which directly determines the quality of the printed product. This study adopted a 23 full-factor Design of Experiment (DoE) with three central points to optimize the printing ink composition of levetiracetam 3D printed dispersible tablet based on the concept of Quality by Design. Firstly, using polyvinyl pyrrolidone K30, glycerin and polysorbate 20 as independent variables based on 40% (v/v) isopropanol aqueous solution, and weight variation, hardness, friability and dispersion uniformity of the printed tablets were used as dependent variables. Then obtained the design space of the printing ink prescription by DoE model analysis, and the response optimizer was used to obtain the optimal printing ink prescription:isopropanol aqueous solution containing 0.1% (w/w) polyvinyl pyrrolidone K30 and 4.0% (w/w) glycerin. The jetting mechanism and wettability of the printing ink were analyzed, and different strengths of personalized 3D printed tablets were prepared and characterized, which verified the rationality of the printing ink formulation. This study provided a reference for the development of printing ink for binder jetting 3D printed preparations.
Key words:    binder jetting technology    3D printing    levetiracetam dispersible tablet    printing ink    design space    jetting mechanism   
收稿日期: 2020-12-10
DOI: 10.16438/j.0513-4870.2020-1904
基金项目: 国家自然科学基金面上项目(82073793);国家科技重大专项-儿童用药品种及关键技术研发项目(2018ZX09721003-007).
通讯作者: 郑爱萍,Tel:86-10-66931694,E-mail:apzheng@163.com
Email: apzheng@163.com
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