Department of Pharmaceutics, UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, UK; Department of Pharmacology, Pharmacy and Pharmaceutical Technology, Paraquasil Group (GI-2109), Faculty of Pharmacy, iMATUS and Health Research Institute of Santiago de Compostela (IDIS), University of Santiago de Compostela (USC), Santiago de Compostela 15782, Spain.
Radiology Department, University Hospital Lucus Augusti (HULA), Rúa Dr. Ulises Romero, 1, Lugo 27003, Spain.
J Control Release. 2024 Jan;365:348-357. doi: 10.1016/j.jconrel.2023.11.022. Epub 2023 Nov 30.
Three-dimensional (3D) printing is revolutionising the way that medicines are manufactured today, paving the way towards more personalised medicine. However, there is limited in vivo data on 3D printed dosage forms, and no studies to date have been performed investigating the intestinal behaviour of these drug products in humans, hindering the complete translation of 3D printed medications into clinical practice. Furthermore, it is unknown whether conventional in vitro release tests can accurately predict the in vivo performance of 3D printed formulations in humans. In this study, selective laser sintering (SLS) 3D printing technology has been used to produce two placebo torus-shaped tablets (printlets) using different laser scanning speeds. The printlets were administered to 6 human volunteers, and in vivo disintegration times were assessed using magnetic resonance imaging (MRI). In vitro disintegration tests were performed using a standard USP disintegration apparatus, as well as an alternative method based on the use of reduced media volume and minimal agitation. Printlets fabricated at a laser scanning speed of 90 mm/s exhibited an average in vitro disintegration time of 7.2 ± 1 min (measured using the USP apparatus) and 25.5 ± 4.1 min (measured using the alternative method). In contrast, printlets manufactured at a higher laser scanning speed of 130 mm/s had an in vitro disintegration time of 2.8 ± 0.8 min (USP apparatus) and 18.8 ± 1.9 min (alternative method). When tested in humans, printlets fabricated at a laser scanning speed of 90 mm/s showed an average disintegration time of 17.3 ± 7.2 min, while those manufactured at a laser scanning speed of 130 mm/s exhibited a shorter disintegration time of 12.7 ± 6.8 min. Although the disintegration times obtained using the alternative method more closely resembled those obtained in vivo, no clear correlation was observed between the in vitro and in vivo disintegration times, highlighting the need to develop better in vitro methodology for 3D printed drug products.
三维（3D）打印正在彻底改变当今药物制造的方式，为更个性化的药物铺平道路。然而，目前关于 3D 打印剂型的体内数据有限，迄今为止尚无研究探讨这些药物产品在人体中的肠道行为，这阻碍了 3D 打印药物完全转化为临床实践。此外，目前尚不清楚常规的体外释放试验是否可以准确预测 3D 打印制剂在人体中的体内性能。在这项研究中，使用选择性激光烧结（SLS）3D 打印技术生产了两种使用不同激光扫描速度的安慰剂 torus 形片剂（打印片）。将这些打印片给 6 名人类志愿者服用，并使用磁共振成像（MRI）评估体内崩解时间。体外崩解试验使用标准 USP 崩解仪以及基于使用减少的介质体积和最小搅拌的替代方法进行。以 90mm/s 的激光扫描速度制造的打印片的平均体外崩解时间为 7.2±1 分钟（使用 USP 仪器测量）和 25.5±4.1 分钟（使用替代方法测量）。相比之下，以 130mm/s 的较高激光扫描速度制造的打印片的体外崩解时间为 2.8±0.8 分钟（USP 仪器）和 18.8±1.9 分钟（替代方法）。在人体中进行测试时，以 90mm/s 的激光扫描速度制造的打印片的平均崩解时间为 17.3±7.2 分钟，而以 130mm/s 的激光扫描速度制造的打印片的崩解时间较短，为 12.7±6.8 分钟。虽然替代方法获得的崩解时间更接近体内获得的时间，但体外和体内崩解时间之间没有观察到明显的相关性，这突出表明需要为 3D 打印药物产品开发更好的体外方法。
