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硝呋替莫的3D打印片剂:体外和体内抗研究

3D-Printed Tablets of Nifurtimox: In Vitro and In Vivo Anti- Studies.

作者信息

Bedogni Giselle R, Lima Ana Luiza, Gross Idejan P, Menezes Tatiana Prata, Talvani Andre, Cunha-Filho Marcilio, Salomon Claudio J

机构信息

Institute of Chemistry Rosario, National Council for Scientific and Technical Research (IQUIR-CONICET), Rosario 2000, Argentina.

Laboratory of Food, Drug, and Cosmetics (LTMAC), School of Health Sciences, University of Brasilia, Brasília 70910-900, Brazil.

出版信息

Pharmaceutics. 2025 Jan 9;17(1):80. doi: 10.3390/pharmaceutics17010080.

Abstract

: Chagas disease is a neglected tropical disease caused by infection with the parasite . Benznidazole and nifurtimox are the only approved drugs for treating this condition, but their low aqueous solubility may lead to erratic bioavailability. This work aimed for the first time to formulate tablets of nifurtimox by hot melt extrusion coupled with 3D printing as a strategy to increase drug dissolution and the production of tablets with dosage on demand. : Different pharmaceutical-grade polymers were evaluated through film casting, and those with promising nifurtimox amorphization capacity were further used to prepare filaments by hot melt extrusion. The printability of the obtained filaments was tested, and the polyvinyl alcohol filament was further used for printing tablets containing 120 and 60 mg of nifurtimox. : Three-dimensional tablets showed a remarkable improvement in the drug dissolution rate compared to commercial tablets and a dissolution efficiency 2.8 times higher. In vivo studies were carried out on Swiss mice. Parasitemia curves of nifurtimox printed tablets were significantly superior to the pure drug. Moreover, NFX 3D tablets provided a similar reduction in plasmatic concentration to benznidazole, the gold-standard drug for acute-phase treatment of the Chagas disease. : The findings of this work showed that hot melt extrusion coupled with 3D printing is a promising alternative for increasing nifurtimox biopharmaceutical properties and an attractive approach for personalized medicine.

摘要

恰加斯病是一种由寄生虫感染引起的被忽视的热带病。苯硝唑和硝呋替莫是治疗该疾病的仅有的获批药物,但它们的低水溶性可能导致生物利用度不稳定。这项工作首次旨在通过热熔挤出结合3D打印来制备硝呋替莫片剂,作为提高药物溶出度和按需生产片剂的一种策略。:通过流延法评估了不同的药用级聚合物,那些具有良好的硝呋替莫非晶化能力的聚合物进一步用于通过热熔挤出制备长丝。测试了所得长丝的可打印性,并且聚乙烯醇长丝进一步用于打印含有120毫克和60毫克硝呋替莫的片剂。:与市售片剂相比,三维片剂的药物溶出率有显著提高,溶出效率高出2.8倍。在瑞士小鼠身上进行了体内研究。硝呋替莫打印片剂的寄生虫血症曲线明显优于纯药物。此外,硝呋替莫3D片剂的血浆浓度降低情况与苯硝唑相似,苯硝唑是恰加斯病急性期治疗的金标准药物。:这项工作的研究结果表明,热熔挤出结合3D打印是提高硝呋替莫生物制药性能的一种有前景的替代方法,也是个性化医疗的一种有吸引力的方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5efd/11768318/36b3a58ad226/pharmaceutics-17-00080-g001.jpg

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