Holländer Jenny, Genina Natalja, Jukarainen Harri, Khajeheian Mohammad, Rosling Ari, Mäkilä Ermei, Sandler Niklas
Pharmaceutical Sciences Laboratory, Abo Akademi University, Turku, Finland.
Pharmaceutical Sciences Laboratory, Abo Akademi University, Turku, Finland; Department of Pharmacy, University of Copenhagen, Copenhagen, Denmark.
J Pharm Sci. 2016 Sep;105(9):2665-2676. doi: 10.1016/j.xphs.2015.12.012. Epub 2016 Feb 20.
The goal of the present study was to fabricate drug-containing T-shaped prototypes of intrauterine system (IUS) with the drug incorporated within the entire backbone of the medical device using 3-dimensional (3D) printing technique, based on fused deposition modeling (FDM™). Indomethacin was used as a model drug to prepare drug-loaded poly(ε-caprolactone)-based filaments with 3 different drug contents, namely 5%, 15%, and 30%, by hot-melt extrusion. The filaments were further used to 3D print IUS. The results showed that the morphology and drug solid-state properties of the filaments and 3D prototypes were dependent on the amount of drug loading. The drug release profiles from the printed devices were faster than from the corresponding filaments due to a lower degree of the drug crystallinity in IUS in addition to the differences in the external/internal structure and geometry between the products. Diffusion of the drug from the polymer was the predominant mechanism of drug release, whereas poly(ε-caprolactone) biodegradation had a minor effect. This study shows that 3D printing is an applicable method in the production of drug-containing IUS and can open new ways in the fabrication of controlled release implantable devices.
本研究的目的是基于熔融沉积建模（FDM™）三维（3D）打印技术，制造含药的宫内节育系统（IUS）T形原型，使药物融入医疗器械的整个骨架中。以吲哚美辛作为模型药物，通过热熔挤出法制备了含3种不同药物含量（即5%、15%和30%）的载药聚己内酯长丝。这些长丝进一步用于3D打印IUS。结果表明，长丝和3D原型的形态及药物固态性质取决于药物载量。由于IUS中药物结晶度较低，以及产品之间外部/内部结构和几何形状的差异，打印装置的药物释放曲线比相应长丝的更快。药物从聚合物中的扩散是药物释放的主要机制，而聚己内酯的生物降解作用较小。本研究表明，3D打印是生产含药IUS的一种适用方法，可为控释植入装置的制造开辟新途径。
