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

Full-factor design of experiment application in the development of printing ink for binder jetting 3D printed preparation

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。

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 3 D 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 3 D printed preparations.