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含抗癌药物5-氟尿嘧啶片剂的粉末滴注3D打印

Drop-On-Powder 3D Printing of Tablets with an Anti-Cancer Drug, 5-Fluorouracil.

作者信息

Shi Kejing, Tan Deck K, Nokhodchi Ali, Maniruzzaman Mohammed

机构信息

School of Life Sciences, University of Sussex, Falmer, Brighton BN1 9QJ, UK.

Drug Applied Research Center and Faculty of Pharmacy, Tabriz University of Medical Sciences, 5166/15731 Tabriz, Iran.

出版信息

Pharmaceutics. 2019 Apr 1;11(4):150. doi: 10.3390/pharmaceutics11040150.

Abstract

This study reports the first case of an innovative drop-on-powder (DoP) three-dimensional (3D) printing technology to produce oral tablets (diameters of 10 mm and 13 mm) loaded with an anticancer model drug, 5-fluorouracil (FLU). For this study, a composition of the powder carrier containing CaSO₄ hydrates, vinyl polymer, and carbohydrate was used as the matrix former, whereas 2-pyrrolidone with a viscosity like water was used as a binding liquid or inkjet ink. All tablets were printed using a commercial ZCorp 3D printer with modification. The resultant tablets were subject to coating with various polymeric solutions containing the drug. The composition of the polymeric solutions was adjusted at drug: polymer(s) 1:1 (/) ratio. Either Soluplus (SOL) alone or in combination with polyethylene glycol (PEG) was used to develop the coating solution of 2.5% (/) concentration. The particle size analysis, flow test, and particle morphology studies revealed mono-modal narrow size distribution, good flow properties, and porous loosely bound texture (of the tablets), respectively. Moreover, the advanced application of the fluorescence microscopy showed a homogenous distribution of the drug throughout the surface of the 3D printed tablets. The dissolution studies showed that the tablet compositions, dimensions, and the coating solution compositions influenced the release of the drug from the tablets. It can be concluded that our innovative DoP 3D printing technology can be used to fabricate personalized dosage forms containing optimized drug content with high accuracy and shape fidelity. This is particularly suitable for those drugs that are highly unstable in thermal processing and cannot withstand the heat treatment, such as in fused deposition modeling (FDM) 3D printing.

摘要

本研究报道了首例采用创新的粉末上滴加(DoP)三维(3D)打印技术制备载有抗癌模型药物5-氟尿嘧啶(FLU)的口服片剂(直径为10毫米和13毫米)。在本研究中,含有硫酸钙水合物、乙烯基聚合物和碳水化合物的粉末载体组合物用作基质形成剂,而粘度似水的2-吡咯烷酮用作粘结液或喷墨油墨。所有片剂均使用经过改装的商用ZCorp 3D打印机进行打印。所得片剂用含有药物的各种聚合物溶液进行包衣。聚合物溶液的组成按药物:聚合物1:1(/)的比例进行调整。单独使用Soluplus(SOL)或与聚乙二醇(PEG)组合使用,以配制浓度为2.5%(/)的包衣溶液。粒度分析、流动性测试和颗粒形态研究分别揭示了单峰窄粒度分布、良好的流动性能以及(片剂的)多孔疏松结合质地。此外,荧光显微镜的进一步应用表明药物在3D打印片剂的整个表面均匀分布。溶出度研究表明,片剂组成、尺寸和包衣溶液组成会影响药物从片剂中的释放。可以得出结论,我们创新的DoP 3D打印技术可用于制造含有优化药物含量、具有高精度和形状保真度的个性化剂型。这特别适用于那些在热加工中高度不稳定且无法承受热处理的药物,例如在熔融沉积建模(FDM)3D打印中。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bcf6/6523964/65ec6b57b097/pharmaceutics-11-00150-g001.jpg

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