Zheng Yu, Deng Feihuang, Wang Bo, Wu Yue, Luo Qing, Zuo Xianghao, Liu Xin, Cao Lihua, Li Min, Lu Haohui, Cheng Senping, Li Xiaoling
Triastek, Inc., 12 East Mozhou Road, U Park P402, Nanjing, Jiangsu, China.
Triastek, Inc., 12 East Mozhou Road, U Park P402, Nanjing, Jiangsu, China.
Int J Pharm. 2021 Jun 1;602:120639. doi: 10.1016/j.ijpharm.2021.120639. Epub 2021 Apr 24.
Three-dimensional printing (3DP) technology offers unique advantages for pharmaceutical applications. However, most of current 3D printing methods and instrumentations are not specifically designed and developed for pharmaceutical applications. To meet the needs in pharmaceutical applications for precision, compatibility with a wide range of pharmaceutical excipients and drug materials without additional processing, high throughput and GMP compliance, an extrusion-based 3D printer based on Melt Extrusion Deposition (MED™) 3D printing technology was developed in this study. This technology can process powder pharmaceutical excipients and drugs directly without the need of preparing filament as required by FDM 3D printing. Six different tablet designs based on compartment models were used to demonstrate the precision and reproducibility of this technology. The designed tablets were fabricated using the GMP-compliant MED™ 3D printer and were evaluated in vitro for drug release and in vivo for selected designs using male beagle dogs. Tablet designs with one or more compartments showed versatile release characteristics in modulating the release onset time, release kinetics, duration of release and mode of release. Multiple drugs or formulations were fabricated into a single tablet to achieve independent release kinetics for each drug or to fine-tune the pharmacokinetic profile of a drug. Building upon the theoretical analysis of models, precision and reproducibility of MED™ 3D printing technology, a novel product development approach, 3D printing formulation by design (3DPFbD®) was developed to provide an efficient tool for fast and efficient pharmaceutical product development. The MED™ 3D printing represents a novel and promising technology platform encompassing design and development of modified drug release products and has potential to impact the drug delivery and pharmaceutical product development.
三维打印（3DP）技术在药物应用方面具有独特优势。然而，当前大多数3D打印方法和仪器并非专门为药物应用设计和开发。为满足药物应用对精度、与多种药物辅料和药物原料的兼容性（无需额外加工）、高通量以及符合药品生产质量管理规范（GMP）的需求，本研究开发了一种基于熔体挤出沉积（MED™）3D打印技术的挤出式3D打印机。该技术可直接处理粉末状药物辅料和药物，无需像熔融沉积成型（FDM）3D打印那样制备长丝。基于隔室模型设计了六种不同的片剂，以证明该技术的精度和可重复性。使用符合GMP标准的MED™ 3D打印机制造设计好的片剂，并对其进行体外药物释放评估，对于选定的设计，还使用雄性比格犬进行体内评估。具有一个或多个隔室的片剂设计在调节释放起始时间、释放动力学、释放持续时间和释放模式方面表现出多样的释放特性。将多种药物或制剂制成单片剂，以使每种药物实现独立的释放动力学，或微调药物的药代动力学特征。基于模型的理论分析、MED™ 3D打印技术的精度和可重复性，开发了一种新的产品开发方法——3D打印设计处方（3DPFbD®），为快速高效的药物产品开发提供了一种有效工具。MED™ 3D打印代表了一个新颖且有前景的技术平台，涵盖改良释药产品的设计与开发，有可能对药物递送和药物产品开发产生影响。
