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水溶性超分子水凝胶的体积打印及非破坏性药物定量分析

Volumetric printing and non-destructive drug quantification of water-soluble supramolecular hydrogels.

作者信息

Ong Jun Jie, Jørgensen Anna Kirstine, Zhu Zilan, Telford Richard, Davies Philip J, Gaisford Simon, Goyanes Alvaro, Basit Abdul W

机构信息

Department of Pharmaceutics, UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London, WC1N 1AX, UK.

School of Chemistry and Biosciences, University of Bradford, Richmond Road, Bradford, BD7 1DP, UK.

出版信息

Drug Deliv Transl Res. 2025 Jun;15(6):2048-2063. doi: 10.1007/s13346-024-01723-6. Epub 2024 Oct 18.

Abstract

Vat photopolymerisation 3D printing is being actively explored for manufacturing personalised medicines due to its high dimensional accuracy and lack of heat application. However, several challenges have hindered its clinical translation, including the inadequate printing speeds, the lack of resins that give soluble matrices, and the need for non-destructive quality control measures. In this study, for the first time, a rapid approach to producing water-soluble vat photopolymerised matrices and a means of non-destructively verifying their drug content were investigated. Volumetric printing, a novel form of vat photopolymerisation, was used to fabricate personalised warfarin-loaded 3D-printed tablets (printlets). Eight different formulations containing varying amounts of warfarin (0.5-6.0% w/w) were used to print two different sized torus-shaped printlets within 6.5 to 11.1 s. Nuclear magnetic resonance (NMR) spectroscopy revealed the presence of only trace amounts of unreacted acrylate monomers, suggesting that the photopolymerisation reaction had occurred to near completion. All printlets completely solubilised and released their entire drug load within 2.5 to 7 h. NIR spectroscopy (NIRS) was used to non-destructively verify the dose of warfarin loaded into the vat photopolymerised printlets. The partial least square regression model built showed strong linearity (R = 0.980), and high accuracy in predicting the drug loading of the test sample (RMSEP = 0.205%). Therefore, this study advances pharmaceutical vat photopolymerisation by demonstrating the feasibility of producing water-soluble printlets via volumetric printing and quantifying the drug load of vat photopolymerised printlets with NIRS.

摘要

由于其高尺寸精度和无需加热,光固化3D打印正被积极探索用于制造个性化药物。然而,一些挑战阻碍了其临床转化,包括打印速度不足、缺乏能提供可溶基质的树脂以及对无损质量控制措施的需求。在本研究中,首次研究了一种快速生产水溶性光固化基质的方法以及无损验证其药物含量的手段。体积打印是一种新型的光固化形式,用于制造个性化的载有华法林的3D打印片剂(打印片)。使用八种含有不同量华法林(0.5 - 6.0% w/w)的不同配方,在6.5至11.1秒内打印出两种不同尺寸的环形打印片。核磁共振(NMR)光谱显示仅存在痕量未反应的丙烯酸酯单体,这表明光聚合反应已接近完全发生。所有打印片在2.5至7小时内完全溶解并释放出全部药物负载。近红外光谱(NIRS)用于无损验证加载到光固化打印片中的华法林剂量。所建立的偏最小二乘回归模型显示出很强的线性(R = 0.980),并且在预测测试样品的药物负载方面具有高精度(RMSEP = 0.205%)。因此,本研究通过证明通过体积打印生产水溶性打印片以及用NIRS定量光固化打印片的药物负载的可行性,推动了药物光固化技术的发展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f248/12037435/2a6545f07a03/13346_2024_1723_Fig2_HTML.jpg

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