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对乙酰氨基酚控释 FDM 3D 打印微丸:制剂变量对可打印性和药物释放的评价。

Paracetamol extended release FDM 3D printlets: Evaluation of formulation variables on printability and drug release.

机构信息

Department of Pharmaceutical Technology and Cosmetology, University of Belgrade - Faculty of Pharmacy, Serbia.

Department of Pharmaceutical Technology and Cosmetology, University of Belgrade - Faculty of Pharmacy, Serbia.

出版信息

Int J Pharm. 2021 Jan 5;592:120053. doi: 10.1016/j.ijpharm.2020.120053. Epub 2020 Nov 5.

DOI:10.1016/j.ijpharm.2020.120053
PMID:33161041
Abstract

Paracetamol printlets were prepared via hot-melt extrusion process and fused deposition modelling, using two types of backbone polymers. Polycaprolactone (PCL) and Polyethylene oxides (PEO) 100 K and 200 K were used, while Arabic gum was used as a plasticizer to facilitate the material flow and Gelucire® 44/14 as an enhancer of drug release. Different drug/polymer ratios were prepared. Extrusion temperature was adjusted according to the mixture/polymer types. It was possible to produce filaments with maximum of 60% w/w of drug. Mechanical properties of filaments were evaluated using three-point bend test, while obtained parameters were modelled using decision tree as a data mining method. Correlation between maximum displacement, maximum force and printability was obtained with accuracy of 84.85% and can be a useful tool for predicting printability of filaments. This study briefly demonstrated that backbone polymer in formulation plays crucial role in obtaining FDM printlets with desired properties. PEO-based filaments were more prone to be clogged in printcore, but their printlets showed much faster drug release. Drug release from all printlets was prolonged: from 50% in 8 h (PCL), to complete release in 4 h (PEO). Paracetamol release kinetics was guided by anomalous transport, attributed to the diffusion and erosion process.

摘要

对乙酰氨基酚片剂是通过热熔挤出工艺和熔融沉积成型技术制备的,使用了两种类型的主链聚合物:聚己内酯(PCL)和聚氧化乙烯(PEO)100K 和 200K,同时使用阿拉伯胶作为增塑剂以促进材料流动,并用 Gelucire®44/14 作为药物释放的增强剂。制备了不同的药物/聚合物比例。根据混合物/聚合物的类型调整挤出温度。可以生产出最大药物含量为 60%w/w 的纤维丝。使用三点弯曲测试评估纤维丝的机械性能,并用决策树作为数据挖掘方法对获得的参数进行建模。最大位移、最大力和可打印性之间的相关性具有 84.85%的准确性,可作为预测纤维丝可打印性的有用工具。本研究简要表明,配方中的主链聚合物在获得具有所需性能的熔融沉积成型片剂方面起着至关重要的作用。基于 PEO 的纤维丝更容易在打印头中堵塞,但它们的片剂显示出更快的药物释放速度。所有片剂的药物释放都延长了:从 8 小时内释放 50%(PCL)到 4 小时内完全释放(PEO)。对乙酰氨基酚的释放动力学由异常传输控制,这归因于扩散和侵蚀过程。

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