Temperature and solvent facilitated extrusion based 3D printing for pharmaceuticals

被引:31
作者
Dores, Filipa [1 ]
Kuzminska, Magdalena [1 ,2 ]
Soares, Cindy [1 ]
Bohus, Marton [1 ]
Shervington, Leroy A. [1 ]
Habashy, Rober [1 ]
Pereira, Beatriz C. [1 ]
Peak, Matthew [3 ]
Isreb, Abdullah [1 ]
Alhnan, Mohamed A. [4 ]
机构
[1] Univ Cent Lancashire, Sch Pharm & Biomed Sci, Preston, Lancs, England
[2] Med Univ Warsaw, Fac Pharm, Lab Med Div, Warsaw, Poland
[3] Alder Hey Childrens NHS Fdn Trust, Paediat Med Res Unit, Liverpool, Merseyside, England
[4] Kings Coll London, Inst Pharmaceut Sci, London, England
关键词
Direct ink writing; Material extrusion; Personalized; Patient-specific; Small batch; Early phase clinical trials; RELEASE; IMMEDIATE; TABLETS; DRUG; DISSOLUTION; FABRICATION; HEALTH; DISPERSION; MATRICES; STATE;
D O I
10.1016/j.ejps.2020.105430
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
On demand manufacturing of patient-specific oral doses provides significant advantages to patients and healthcare staff. Several 3D printing (3DP) technologies have been proposed as a potential digital alternative to conventional manufacturing of oral tablets. For an additive manufacturing approach to be successful for on-demand preparation, a facile process with minimal preparation steps and training requirements is needed. A novel hybrid approach to the 3D printing process is demonstrated here based on combining both a solvent and heating to facilitate extrusion. The system employed a moderate elevated temperature range (65-100 degrees C), a brief drying period, and a simple set-up. In this approach, a compact material cylinder is used as a pharmaceutical ink to be extruded in a temperature-controlled metal syringe. The process proved compatible with hygroscopic polymers [Poly(vinyl alcohol (PVA) and polyvinylpyrrolidone (PVP)] and a number of pharmaceutical fillers (lactose, sorbitol and D-mannitol). The fabricated tablets demonstrated acceptable compendial weight and content uniformity as well as mechanical resistance. In vitro drug release of theophylline from 3D printed tablets was dependent on the nature of the polymer and its molecular weight. This reported approach offers significant advantages compared to other 3DP technologies: simplification of pre-product, the use of a moderate tem-perature range, a minimal drying period, and avoiding the use of mechanically complicated machinery. In the future, we envisage the use of this low-cost and facile approach to fabricate small batches of bespoke tablets.
引用
收藏
页数:9
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