一项关于使用聚合物共混物来改善通过熔融沉积建模(FDM)3D打印制备的药物固体分散体的可印刷性并调节其药物释放的研究。

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.

作者信息

Alhijjaj Muqdad, Belton Peter, Qi Sheng

机构信息

School of Pharmacy, University of East Anglia, Norwich, Norfolk NR4 7TJ, UK; Department of Pharmaceutics, College of Pharmacy, University of Basrah, Basrah, Iraq.

School of Chemistry, University of East Anglia, Norwich, Norfolk NR4 7TJ, UK.

出版信息

Eur J Pharm Biopharm. 2016 Nov;108:111-125. doi: 10.1016/j.ejpb.2016.08.016. Epub 2016 Sep 2.

Abstract

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 clear 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.

摘要

熔融沉积成型(FDM)3D打印最近在个性化固体口服制剂生产方面吸引了越来越多的研究关注。然而,市售的FDM打印机在可加工材料方面极为有限,仅限于少数几种热塑性聚合物,而这些聚合物往往既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一种制剂策略,以克服这一加工性能问题,并使打印分散体具有可调节的药物释放速率。使用FDM 3D打印技术,将模型药物非洛地平与聚乙二醇(PEG)、聚环氧乙烷(PEO)和吐温80与尤特奇E PO或固体分散体(Soluplus)的聚合物共混物成功制备了固体分散体。由于聚乙烯醇(PVA)是FDM 3D打印中使用最广泛的聚合物之一,因此以PVA为基础的固体分散体作为基准,在加工性能方面将聚合物共混体系与之进行比较。聚合物共混物表现出优异的可打印性,适合使用市售的FDM 3D打印机进行加工。载药量为10%时,所有表征数据表明模型药物在基质中呈分子分散状态。在体外溶出试验中,很明显制剂的崩解行为显著影响药物释放速率。基于尤特奇EPO的共混分散体表现出整体崩解;而基于固体分散体的共混物则表现出逐条“剥离”式崩解。结果表明,共混物中辅料之间的混溶性、材料在溶出介质中的溶解度以及FDM过程中打印条带之间的融合程度之间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打印的控释制剂设计原则带来了新的见解。

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