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

IF 5.7 3区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Jun Jie Ong, Anna Kirstine Jørgensen, Zilan Zhu, Richard Telford, Philip J Davies, Simon Gaisford, Alvaro Goyanes, Abdul W Basit
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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 (R2 = 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.

水溶性超分子水凝胶的体积打印和无损药物定量。
大桶光聚合三维打印因其尺寸精度高、无需加热等优点,正被积极探索用于制造个性化药品。然而,一些挑战阻碍了它的临床应用,包括打印速度不够快、缺乏可提供可溶性基质的树脂以及需要非破坏性的质量控制措施。本研究首次研究了一种快速生产水溶性大桶光聚合基质的方法,以及一种非破坏性验证其药物含量的方法。体积打印是大桶光聚合的一种新形式,用于制造个性化的华法林三维打印片剂(printlets)。核磁共振(NMR)光谱显示仅存在微量未反应的丙烯酸酯单体,表明光聚合反应已接近完成。所有小印片都在 2.5 至 7 小时内完全溶解并释放出全部药物负荷。近红外光谱(NIRS)被用来非破坏性地验证装入槽式光聚合小印片中的华法林剂量。建立的偏最小二乘法回归模型显示出较强的线性关系(R2 = 0.980),并能准确预测测试样品的药物负载量(RMSEP = 0.205%)。因此,本研究证明了通过体积印刷生产水溶性小印片的可行性,并利用近红外光谱量化了大桶光聚合小印片的药物负载,从而推动了制药大桶光聚合技术的发展。
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来源期刊
Drug Delivery and Translational Research
Drug Delivery and Translational Research MEDICINE, RESEARCH & EXPERIMENTALPHARMACOL-PHARMACOLOGY & PHARMACY
CiteScore
11.70
自引率
1.90%
发文量
160
期刊介绍: The journal provides a unique forum for scientific publication of high-quality research that is exclusively focused on translational aspects of drug delivery. Rationally developed, effective delivery systems can potentially affect clinical outcome in different disease conditions. Research focused on the following areas of translational drug delivery research will be considered for publication in the journal. Designing and developing novel drug delivery systems, with a focus on their application to disease conditions; Preclinical and clinical data related to drug delivery systems; Drug distribution, pharmacokinetics, clearance, with drug delivery systems as compared to traditional dosing to demonstrate beneficial outcomes Short-term and long-term biocompatibility of drug delivery systems, host response; Biomaterials with growth factors for stem-cell differentiation in regenerative medicine and tissue engineering; Image-guided drug therapy, Nanomedicine; Devices for drug delivery and drug/device combination products. In addition to original full-length papers, communications, and reviews, the journal includes editorials, reports of future meetings, research highlights, and announcements pertaining to the activities of the Controlled Release Society.
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