Laboratory of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium; Pharmacy Department, Faculty of Pharmacy, Nursing and Health Professions, Birzeit University, Palestine.
Laboratory for Microbiology, Parasitology and Hygiene (LMPH), Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp, Belgium; Mechanical and Mechatronics Engineering Department, Faculty of Engineering & Information Technology, An-Najah National University, Palestine.
Int J Pharm. 2021 Sep 25;607:120922. doi: 10.1016/j.ijpharm.2021.120922. Epub 2021 Jul 23.
Personalized medicine, produced through 3D printing, is a promising approach for delivering the required drug dose based on the patient's profile. The primary purpose of this study was to investigate the potential of two different extrusion-based additive manufacturing techniques - fused filament fabrication (FFF) and screw-based 3D printing, also known as direct extrusion additive manufacturing (DEAM). Different ethylene-vinyl acetate (EVA) copolymers (9 %VA, 12 %VA, 16 %VA, 18 %VA, 25 %VA, 28 %VA, and 40 %VA) were selected and loaded with 50% (w/w) metoprolol tartrate (MPT). Hot-melt extrusion was performed to produce the drug-loaded filaments. These filaments were used for FFF in which the mechanical and rheological properties were rate-limiting steps. The drug-loaded filament based on the 18 %VA polymer was the only printable formulation due to its appropriate mechanical and rheological properties. As for the highest VA content (40 %VA), the feeding pinch rolls cause buckling of the filaments due to insufficient stiffness, while other filaments were successfully feedable towards the extrusion nozzle. However, poor flowability out of the extrusion nozzle due to the rheological limitation excluded these formulations from the initial printing trials. Filaments were also pelletized and used for pellets-DEAM. This method showed freedom in formulation selection because the screw rotation drives the material flow with less dependence on their mechanical properties. All drug-loaded pellets were successfully printed via DEAM, as sufficient pressure was built up towards the nozzle due to single screw extrusion processing method. In contrast, filaments were used as a piston to build up the pressure required for extrusion in filament-based printing, which highly depends on the filament's mechanical properties. Moreover, printing trials using a physical mixture in powder form were also investigated and showed promising results. In vitro drug release showed similar release patterns for MPT-loaded 3D printed tablets regardless of the printing technique. Additionally, pellets-DEAM enabled the production of tablets with the highest VA content, which failed in FFF 3D printing but showed an interesting delayed release profile.
个性化医学是一种有前途的方法，通过 3D 打印，可以根据患者的个人资料提供所需的药物剂量。本研究的主要目的是研究两种不同的挤出式增材制造技术的潜力 - 熔融沉积成型（FFF）和螺杆式 3D 打印，也称为直接挤出增材制造（DEAM）。选择了不同的乙烯-醋酸乙烯酯（EVA）共聚物（9%VA、12%VA、16%VA、18%VA、25%VA、28%VA 和 40%VA），并负载了 50%（重量/重量）酒石酸美托洛尔（MPT）。进行热熔挤出以生产载药丝。这些丝用于 FFF，其中机械和流变性能是限速步骤。基于 18%VA 聚合物的载药丝是唯一可打印的配方，因为其具有适当的机械和流变性能。对于最高 VA 含量（40%VA），由于刚度不足，进料夹辊会导致丝的弯曲，而其他丝可以成功地朝向挤出喷嘴进料。然而，由于流变限制，挤出喷嘴外的流动性差，这些配方被排除在初始打印试验之外。丝也被制粒并用于粒料-DEAM。这种方法在配方选择方面具有自由度，因为螺杆旋转驱动材料流动，对其机械性能的依赖性较小。由于采用单螺杆挤出加工方法，所有载药粒料都成功地通过 DEAM 打印，因为在喷嘴处建立了足够的压力。相比之下，丝用作在基于丝的打印中建立挤出所需压力的活塞，这高度依赖于丝的机械性能。此外，还研究了使用粉末形式的物理混合物的打印试验，结果也很有前景。体外药物释放显示出 MPT 负载的 3D 打印片剂具有相似的释放模式，无论使用哪种打印技术。此外，粒料-DEAM 能够生产含有最高 VA 含量的片剂，这在 FFF 3D 打印中失败，但显示出有趣的延迟释放模式。
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