An investigation into the use of polymer blends to improve the printability of and regulate drug release from pharmaceutical solid dispersions prepared via fused deposition modeling (FDM) 3D printing
An investigation into the use of polymer blends to improve the printability of and regulate drug release from pharmaceutical solid dispersions prepared via fused deposition modeling (FDM) 3D printing
复制标题
DOI：
10.1016/j.ejpb.2016.08.016
复制
发表时间：
2016-11-01
影响因子：
4.9
通讯作者：
Qi, Sheng
中科院分区：
文献类型：
--
作者：
Alhijjaj, Muqdad;Belton, Peter;Qi, Sheng
FDM 3D 打印最近吸引了越来越多的研究努力来生产个性化固体口服制剂。然而，商用 FDM 打印机在可加工为几种热塑性聚合物的材料方面极为有限，这些聚合物通常可能不是药学上批准的材料，也不是优化难溶性化合物剂型性能的理想材料。本研究探索了使用聚合物共混物作为配方策略来克服这一加工性问题，并提供可调节的印刷分散体药物释放速率。使用 FDM 3D 打印技术，使用 PEG、PEO 和 Tween 80 与 Eudragit E PO 或 Soluplus 的聚合物共混物成功制造了模型药物非洛地平的固体分散体。由于 PVA 是 FDM 3D 打印中使用最广泛的聚合物之一，因此使用基于 PVA 的固体分散体作为基准来比较聚合物共混系统的可加工性。该聚合物共混物表现出优异的印刷适性，适合使用市售 FDM 3D 打印机进行加工。载药量为 10% 时，所有表征数据均表明模型药物以分子形式分散在基质中。在体外溶出度测试中，很明显制剂的崩解行为显着影响药物释放速率。基于 Eudragit EPO 的共混分散体表现出整体崩解；而基于 Soluplus 的共混物显示出逐条剥离的“剥离”式分解。结果表明，共混物中赋形剂之间的混溶性、材料在溶出介质中的溶解度以及 FDM 过程中印刷条之间的融合程度的相互作用可用于控制分散体的药物释放速率。这为使用 FDM 3D 打印的控释制剂的设计原理带来了新的见解。 (C) 2016 Elsevier B.V. 保留所有权利。
FDM 3D printing has been recently attracted increasing research efforts towards the production of personalized solid oral formulations. However, commercially available FDM printers are extremely limited with regards to the materials that can be processed to few types of thermoplastic polymers, which often may not be pharmaceutically approved materials nor ideal for optimizing dosage form performance of poor soluble compounds. This study explored the use of polymer blends as a formulation strategy to overcome this processability issue and to provide adjustable drug release rates from the printed dispersions. Solid dispersions of felodipine, the model drug, were successfully fabricated using FDM 3D printing with polymer blends of PEG, PEO and Tween 80 with either Eudragit E PO or Soluplus. As PVA is one of most widely used polymers in FDM 3D printing, a PVA based solid dispersion was used as a benchmark to compare the polymer blend systems to in terms of processability. The polymer blends exhibited excellent printability and were suitable for processing using a commercially available FDM 3D printer. With 10% drug loading, all characterization data indicated that the model drug was molecularly dispersed in the matrices. During in vitro dissolution testing, it was dear that the disintegration behavior of the formulations significantly influenced the rates of drug release. Eudragit EPO based blend dispersions showed bulk disintegration; whereas the Soluplus based blends showed the 'peeling' style disintegration of strip-by strip. The results indicated that interplay of the miscibility between excipients in the blends, the solubility of the materials in the dissolution media and the degree of fusion between the printed strips during FDM process can be used to manipulate the drug release rate of the dispersions. This brings new insight into the design principles of controlled release formulations using FDM 3D printing. (C) 2016 Elsevier B.V. All rights reserved.