Kempin Wiebke, Franz Christian, Koster Lynn-Christine, Schneider Felix, Bogdahn Malte, Weitschies Werner, Seidlitz Anne
Institute of Pharmacy, Center of Drug Absorption and Transport, University of Greifswald, 17487 Greifswald, Germany.
Institute of Pharmacy, Center of Drug Absorption and Transport, University of Greifswald, 17487 Greifswald, Germany.
Eur J Pharm Biopharm. 2017 Jun;115:84-93. doi: 10.1016/j.ejpb.2017.02.014. Epub 2017 Feb 20.
The 3D printing technique of fused deposition modeling® (FDM) has lately come into focus as a potential fabrication technique for pharmaceutical dosage forms and medical devices that allows the preparation of delivery systems with nearly any shape. This is particular promising for implants administered at application sites with a high anatomical variability where an individual shape adaption appears reasonable. In this work different polymers (Eudragit®RS, polycaprolactone (PCL), poly(l-lactide) (PLLA) and ethyl cellulose (EC)) were evaluated with respect to their suitability for FDM of drug loaded implants and their drug release behaviour was evaluated. The fluorescent dye quinine was used as a model drug to visualize drug distribution in filaments and implants. Quinine loaded filaments were produced by solvent casting and subsequent hot melt extrusion (HME) and model implants were printed as hollow cylinders using a standard FDM printer. Parameters were found at which model implants (hollow cylinders, outer diameter 4-5mm, height 3mm) could be produced from all tested polymers. The drug release which was examined by incubation of the printed implants in phosphate buffered saline solution (PBS) pH 7.4 was highly dependent on the used polymer. The fastest relative drug release of approximately 76% in 51days was observed for PCL and the lowest for Eudragit®RS and EC with less than 5% of quinine release in 78 and 100days, respectively. For PCL further filaments were prepared with different quinine loads ranging from 2.5% to 25% and thermal analysis proved the presence of a solid dispersion of quinine in the polymer for all tested concentrations. Increasing the drug load also increased the overall percentage of drug released to the medium since nearly the same absolute amount of quinine remained trapped in PCL at the end of drug release studies. This knowledge is valuable for future developments of printed implants with a desired drug release profile that might be controlled by the choice of the polymer and the drug load.
熔融沉积成型（FDM）3D打印技术最近成为制备药物剂型和医疗器械的一种潜在制造技术，该技术能够制备出几乎任意形状的给药系统。对于植入部位解剖结构差异大，需要定制个性化形状的植入物而言，这一技术极具前景。在本研究中，评估了不同聚合物（Eudragit®RS、聚己内酯（PCL）、聚左旋乳酸（PLLA）和乙基纤维素（EC））在用于药物负载植入物FDM方面的适用性，并对其药物释放行为进行了评估。使用荧光染料奎宁作为模型药物，以观察药物在长丝和植入物中的分布情况。通过溶剂浇铸和随后的热熔挤出（HME）制备了负载奎宁的长丝，并使用标准FDM打印机将模型植入物打印成空心圆柱体。研究发现了使用所有测试聚合物制备模型植入物（空心圆柱体，外径4-5mm，高度3mm）的参数。通过将打印的植入物在pH值为7.4的磷酸盐缓冲盐溶液（PBS）中孵育来检测药物释放情况，结果表明药物释放高度依赖于所使用的聚合物。在51天内，PCL的相对药物释放速度最快，约为76%；Eudragit®RS和EC的药物释放速度最慢，在78天和100天内，奎宁释放量分别不到5%。对于PCL，进一步制备了不同奎宁负载量（2.5%至25%）的长丝，热分析证明在所有测试浓度下，聚合物中均存在奎宁的固体分散体。增加药物负载量也增加了释放到介质中的药物总百分比，因为在药物释放研究结束时，几乎相同绝对量的奎宁仍被困在PCL中。这些知识对于未来开发具有所需药物释放曲线的打印植入物具有重要价值，这种药物释放曲线可能通过聚合物的选择和药物负载量来控制。
