School of Pharmacy, International Campus, Tehran University of Medical Sciences, Tehran, Iran.
Department of Obstetrics and Gynecology, School of Medicine, Vali Asr Hospital, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran.
J Biomed Mater Res A. 2024 Jan;112(1):20-30. doi: 10.1002/jbm.a.37603. Epub 2023 Sep 11.
The objective of the study was to fabricate tailored extended-release tablets of blood thinner Ticagrelor as once-daily dosing using additive manufacturing for better compliance in heart failure therapy. The solid work design of the tablet was printed using hot melt extrusion (HME) based 3D printing by optimized mixture of Eudragit RS-100, plasticizer and drug for producing extrudable and printable filaments. FTIR and TGA results showed no covalent interaction among ingredients and no decomposition during HME process, respectively. Friability, weight variation, assay and content uniformity tests met USP requirements, while the mean hardness of the tablets was calculated in a value between 40 and 50 kg. According to DSC and XRD results, the crystallinity state of the Ticagrelor was converted to an amorphous one in the tablet matrix. Smooth surfaces with multiple deposited layers were observed using SEM. In comparison, the maximum Ticagrelor release of 100% after 120 min from Brilinta® tablets was decreased to 97% in 400 min from the 3D tablet at infill of 90%. Korsmeyer-Peppas kinetic model showed the drug release mechanism is affected by diffusion and swelling. In general, fabrication of the extended-release 3D printed tablet of Ticagrelor using HME-based-additive manufacturing has the potential to provide specific doses with tailored kinetic release for personalized medicine, improving adherence at point-of-care.
本研究的目的是通过添加制造技术来制备定制的、可延长释放时间的抗血小板药物替格瑞洛片剂，以便在心力衰竭治疗中更好地提高顺应性。采用热熔挤出（HME）的 3D 打印技术，通过优化 Eudragit RS-100、增塑剂和药物的混合物，对片剂的实体设计进行打印，以生产出可挤出和可打印的长丝。傅里叶变换红外光谱（FTIR）和热重分析（TGA）结果分别表明各成分之间没有共价相互作用，且在 HME 过程中没有分解。脆碎度、重量差异、含量和均匀度测试均符合 USP 要求，而片剂的平均硬度值计算结果在 40 到 50kg 之间。根据差示扫描量热法（DSC）和 X 射线衍射（XRD）结果，片剂基质中替格瑞洛的结晶状态转变为无定形状态。扫描电子显微镜（SEM）观察到表面光滑，有多层堆积。相比之下，Brilinta®片剂中替格瑞洛的最大释放量在 120 分钟后达到 100%，而在填充率为 90%的 3D 片剂中，400 分钟后释放量下降至 97%。Korsmeyer-Peppas 动力学模型表明，药物释放机制受扩散和溶胀的影响。总体而言，采用基于 HME 的添加剂制造技术制备替格瑞洛的延长释放 3D 打印片剂，有望为个性化医疗提供具有特定剂量和定制释放动力学的药物，从而改善患者在接受治疗时的顺应性。
