Department of Pharmaceutical Technology and Cosmetology, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11221 Belgrade, Serbia.
Department of Pharmaceutical Technology and Cosmetology, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11221 Belgrade, Serbia.
Int J Pharm. 2021 Dec 15;610:121261. doi: 10.1016/j.ijpharm.2021.121261. Epub 2021 Nov 4.
The aim of this study was to investigate the impact of infill patterns on the drug release of 3D-printed tablets and the possibility of tailoring drug release through the use of excipients. Furthermore, the influence of wall thickness was evaluated. Amlodipine was used as a model drug, polyvinyl alcohol (PVA) as a polymer and excipients including sodium starch glycolate (SSG) and hydroxypropyl methyl cellulose (HPMC) HME 4 M were used. Four different formulations were prepared. Firstly, the substances were mixed and then extruded by hot melt extrusion to form filaments. The obtained filaments were used to print amlodipine tablets by fused deposition modeling (FDM) 3D-printing technique. Each formulation was printed in four different infill patterns: zigzag, cubic, tri-hexagon and concentric, while infill density remained constant (20%). The mechanical properties of the obtained filaments were also evaluated using three-point bend test. Amlodipine tablets were printed with varying wall thickness (1 mm, 2 mm and 3 mm) and varying infill patterns. With regard to the infill patterns, higher drug release was achieved with zigzag infill pattern. The simultaneous effect of excipients and infill patterns on amlodipine release has been described and modeled through self - organizing maps (SOMs), which visualize the effect of these variables. Self-organizing maps confirmed the fastest drug release when the zigzag pattern and SSG were used, but also showed that the presence of HPMC HME 4 M was not decisive for drug release rate. As for the wall thickness, higher drug release was achieved with decreasing wall thickness. The results indicated that proper selection of excipients and/or adjusting the infill pattern and wall thickness are ways of tailoring drug release in FDM 3D printing. This study draws the attention to the importance of adjusting the settings of the printer and the usage of excipients to produce release-tailored medications.
本研究旨在探讨填充模式对 3D 打印片剂药物释放的影响，以及通过使用辅料来定制药物释放的可能性。此外，还评估了壁厚的影响。氨氯地平被用作模型药物，聚乙烯醇（PVA）作为聚合物，以及包括交联羧甲基淀粉钠（SSG）和羟丙甲纤维素（HPMC）HME 4M 在内的辅料。制备了四种不同的配方。首先，将物质混合，然后通过热熔挤出将其挤出形成长丝。通过熔融沉积建模（FDM）3D 打印技术，将获得的长丝用于打印氨氯地平片剂。每种配方均以四种不同的填充图案打印：之字形、立方体形、三角六边形和同心形，而填充密度保持不变（20%）。还使用三点弯曲试验评估了获得的长丝的机械性能。打印了具有不同壁厚（1mm、2mm 和 3mm）和不同填充图案的氨氯地平片剂。关于填充图案，之字形填充图案的药物释放率更高。通过自组织映射（SOM）描述和建模了辅料和填充图案对氨氯地平释放的同时影响，SOM 可视化了这些变量的影响。自组织映射证实，当使用之字形图案和 SSG 时，药物释放最快，但也表明 HPMC HME 4M 的存在对药物释放速率并非决定性的。至于壁厚，随着壁厚的减小，药物释放率更高。结果表明，适当选择辅料和/或调整填充图案和壁厚是在 FDM 3D 打印中定制药物释放的方法。本研究提请注意调整打印机设置和使用辅料以生产释放定制药物的重要性。
