Abdollahi Azin, Ansari Zahra, Akrami Mohammad, Haririan Ismaeil, Dashti-Khavidaki Simin, Irani Mohammad, Kamankesh Mojtaba, Ghobadi Emad
School of Pharmacy, International Campus, Tehran University of Medical Sciences, Tehran 1416634793, Iran.
Department of Surgery and Radiology, Faculty of Veterinary Medicine, University of Tehran, Tehran 1416634793, Iran.
Materials (Basel). 2023 Jul 10;16(14):4927. doi: 10.3390/ma16144927.
An extended-release tablet of tacrolimus as once-daily dosing was fabricated using 3D printing technology. It was developed by combining two 3D-printing methods in parallel. Indeed, an optimized mixture of PVA, sorbitol, and magnesium stearate as a shell compartment was printed through a hot-melt extrusion (HME) nozzle while an HPMC gel mixture of the drug in the core compartment was printed by a pressure-assisted micro-syringe (PAM). A 3D-printed tablet with an infill of 90% was selected as an optimized formula upon the desired dissolution profile, releasing 86% of the drug at 12 h, similar to the commercial one. The weight variation, friability, hardness, assay, and content uniformity determination met USP requirements. A microbial evaluation showed that the 3D-printed tablet does not support microbial growth. SEM analysis showed smooth surfaces with multiple deposited layers. No peak interference appeared based on FTIR analysis. No decomposition of the polymer and drug was observed in the printing temperature, and no change in tacrolimus crystallinity was detected based on TGA and DSC analyses, respectively. The novel, sTable 3D-printed tablet, fabricated using controllable additive manufacturing, can quickly provide tailored dosing with specific kinetic release for personalized medicine at the point-of-care.
采用3D打印技术制备了他克莫司缓释片，每日给药一次。它是通过并行结合两种3D打印方法开发的。实际上，作为包衣层的聚乙烯醇（PVA）、山梨醇和硬脂酸镁的优化混合物通过热熔挤出（HME）喷嘴进行打印，而药物在片芯层的羟丙基甲基纤维素（HPMC）凝胶混合物则通过压力辅助微注射器（PAM）进行打印。根据所需的溶出曲线，选择填充率为90%的3D打印片剂作为优化配方，在12小时时释放86%的药物，与市售产品相似。重量差异、脆碎度、硬度、含量测定和含量均匀度测定均符合美国药典要求。微生物评估表明，3D打印片剂不支持微生物生长。扫描电子显微镜（SEM）分析显示表面光滑，有多个沉积层。基于傅里叶变换红外光谱（FTIR）分析未出现峰干扰。在打印温度下未观察到聚合物和药物的分解，分别基于热重分析（TGA）和差示扫描量热法（DSC）分析未检测到他克莫司结晶度的变化。这种使用可控增材制造技术制造的新型稳定3D打印片剂可以在护理点快速提供具有特定动力学释放的定制剂量，以实现个性化医疗。
