Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Mille International ApS, Hellerup, Denmark.
Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Eur J Pharm Sci. 2022 Nov 1;178:106280. doi: 10.1016/j.ejps.2022.106280. Epub 2022 Aug 28.
Additive manufacturing allows for designing innovative properties to pharmaceutical products. Binder jetting (BJ) 3D printing is one of the key techniques within innovative manufacturing. In this study, a structured approach according to the Quality by Design (QbD) principles was implemented to explore the factors affecting fabrication of drug-loaded products produced by BJ 3D printing. The investigated factors included the weight ratio of binder in primary powder and the process parameters related to printing (layer thickness and number of layers). Critical quality attributes, namely disintegration time, tensile strength, friability, dimensions (diameter and height accuracies), residual water content, weight and drug loading were determined based on the quality target product profile of a tablet analogue. The experimental results with a 2-level full factorial design were modeled by multiple linear regression. It was found that binder content was an important factor determining the integrity of the printed products, and the formation of the microstructure of the product was affected by multiple material properties and process parameters. QbD is a systematic and effective approach providing mechanistic understanding of BJ 3D printing and allowing for an efficient design of products with the desired quality.
增材制造允许设计创新的药物产品特性。粘合剂喷射（BJ）3D 打印是创新制造中的关键技术之一。在这项研究中，根据质量源于设计（QbD）原则实施了一种结构化方法，以探索影响 BJ 3D 打印生产载药产品制造的因素。研究的因素包括初级粉末中粘合剂的重量比和与打印相关的工艺参数（层厚和层数）。根据片剂类似物的质量目标产品概况，确定了关键质量属性，即崩解时间、拉伸强度、脆性、尺寸（直径和高度精度）、残余含水量、重量和载药量。使用 2 水平完全因子设计的实验结果通过多元线性回归进行建模。结果表明，粘合剂含量是决定打印产品完整性的重要因素，产品的微观结构形成受到多种材料特性和工艺参数的影响。QbD 是一种系统有效的方法，为 BJ 3D 打印提供了机械理解，并允许设计具有所需质量的产品。
