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

被引:201
作者
Alhijjaj, Muqdad [1 ,2 ]
Belton, Peter [3 ]
Qi, Sheng [1 ]
机构
[1] Univ East Anglia, Sch Pharm, Norwich NR4 7TJ, Norfolk, England
[2] Univ Basrah, Coll Pharm, Dept Pharmaceut, Basrah, Iraq
[3] Univ East Anglia, Sch Chem, Norwich NR4 7TJ, Norfolk, England
关键词
FDM 3D printing; Solid dispersions; Hot melt extrusion; Poorly soluble drugs; Polymer blends; HOT-MELT EXTRUSION; DISSOLUTION ENHANCEMENT; FABRICATION; SOLUBILITY; STABILIZATION; COMBINATIONS; FELODIPINE; IMMEDIATE; DEVICES; TABLETS;
D O I
10.1016/j.ejpb.2016.08.016
中图分类号
R9 [药学];
学科分类号
100702 [药剂学];
摘要
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.
引用
收藏
页码:111 / 125
页数:15
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