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热熔挤出-熔融沉积成型3D打印聚环氧乙烷片剂:溶胀和药物释放的溶出成像分析

Hot-melt extruded-FDM 3D-printed polyethylene oxide tablets: Dissolution imaging analysis of swelling and drug release.

作者信息

Muhamad Haja, Bashir Abdul Basit, Charlton-Harrison James, Abdulhussain Rand, Mawla Nihad, Patel Krishan, Williamson James, Blunt Liam, Walton Karl, Conway Barbara, Asare-Addo Kofi

机构信息

Department of Pharmacy, University of Huddersfield, Huddersfield HD1 3DH UK.

School of Computing and Engineering, University of Huddersfield, Huddersfield HD1 3DH UK.

出版信息

Eur J Pharm Biopharm. 2025 Mar;208:114636. doi: 10.1016/j.ejpb.2025.114636. Epub 2025 Jan 22.

Abstract

Recent developments in pharmacogenetics have emphasised the importance of customised medication, driving interest in technologies like FDM 3D-printing for tailored drug delivery. FDM 3D-printing is a promising technique for the on-demand manufacturing of customised oral dosage forms, providing flexibility in terms of shape and size, dose and drug release profiles. This study investigates the fabrication and characterisation of 3D-printed oral dosage forms using PEO as the primary polymer and PEG 6 K as a plasticiser. Firstly, the printability of the PEO filaments with different propranolol hydrochloride concentrations was explored using the hot-melt extrusion technology. The influence of the propranolol hydrochloride concentrations on the mechanical properties of the filaments was examined was then examined after which surface characteristics, including roughness and wettability, were evaluated. Dissolution imaging was used to visualise the effects of drug content on the swelling and dissolution characteristics of the PEO-based 3D-printed tablets. Results showed a reduction in the flexural stress of the filaments with increasing drug load. It was also observed that increasing the drug load led to higher surface roughness and lower contact angles of the 3D-printed PEO tablets, implying increased surface hydrophilicity. The swelling behaviour of the tablets increased with higher drug concentrations, resulting in a larger gel layer formation. When comparing the drug release percentages, the release rate was higher in the 10 mg propranolol tablets, suggesting that a lower drug content led to a faster release. The greater gel layer of the 40 mg PPN tablets hindered the drug release by acting as a diffusion barrier, while the 10 mg PPN tablets, with less swelling and gel formation, experienced a faster drug release. These findings show the importance of drug content in modifying the surface properties, swelling behaviour, and drug release profiles of 3D-printed PEO tablets. The study also demonstrates the novel use of dissolution imaging for 3D-printed dosage forms, providing valuable quantitative and qualitative insights into swelling dynamics and channel formation to optimise 3D-printed tablets for drug delivery systems.

摘要

药物遗传学的最新进展强调了定制药物的重要性,激发了人们对如熔融沉积成型(FDM)3D打印等用于定制药物递送技术的兴趣。FDM 3D打印是一种很有前景的技术,可用于按需制造定制的口服剂型,在形状和尺寸、剂量以及药物释放曲线方面提供了灵活性。本研究调查了以聚环氧乙烷(PEO)作为主要聚合物和聚乙二醇6000(PEG 6K)作为增塑剂的3D打印口服剂型的制造及特性。首先,使用热熔挤出技术探索了不同盐酸普萘洛尔浓度的PEO长丝的可打印性。接着研究了盐酸普萘洛尔浓度对长丝机械性能的影响,之后评估了包括粗糙度和润湿性在内的表面特性。使用溶出成像来可视化药物含量对基于PEO的3D打印片剂的溶胀和溶解特性的影响。结果表明,随着药物负载量的增加,长丝的弯曲应力降低。还观察到,增加药物负载量会导致3D打印的PEO片剂的表面粗糙度更高和接触角更低,这意味着表面亲水性增加。片剂的溶胀行为随着药物浓度的升高而增加,导致形成更大的凝胶层。比较药物释放百分比时,10mg普萘洛尔片剂的释放速率更高,这表明较低的药物含量导致更快的释放。40mg普萘洛尔片剂更大的凝胶层通过充当扩散屏障阻碍了药物释放,而10mg普萘洛尔片剂溶胀和凝胶形成较少,药物释放较快。这些发现表明药物含量在改变3D打印PEO片剂的表面性质、溶胀行为和药物释放曲线方面的重要性。该研究还展示了溶出成像在3D打印剂型中的新应用,为溶胀动力学和通道形成提供了有价值的定量和定性见解,以优化用于药物递送系统的3D打印片剂。

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