Visualizing disintegration of 3D printed tablets in humans using MRI and comparison with in vitro data

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.

Highlights

• The disintegration of SLS 3D-printed tablets was evaluated for the first time in human volunteers.
• MRI is a useful tool for monitoring 3D printed tablet disintegration in vivo.
• Tablets printed with a lower laser scanning speed had longer disintegration times.
• No correlation was observed between in vitro and in vivo disintegration times.

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.

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Materials

Hydroxypropyl cellulose (HPC) grades -L (140,000 g/mol), -SL (100,000 g/mol), -SSL (40,000 g/mol), and -UL (20,000 g/mol) were obtained from NISSO (Tokyo, Japan). Candurin® Gold Sheen was purchased from Merck KGaA (Darmstadt, Germany). Manganese (II) chloride tetrahydrate (MnCl2) FCC grade was obtained from Cenic Chemicals Ltd. (Vale of Glamorgan, UK). Iron (III) oxide was obtained from Fisher Scientific (Leicestershire, UK). Iron (II) sulfate heptahydrate and ammonium iron (III) citrate were obtained from Sigma-Aldrich (Dorset, UK). Fumed Silica was purchased from Evonik Industries AG (Essen, Germany).

Iria Seoane-Viaño, Tania Pérez-Ramos, Jiaqi Liu, Patricija Januskaite, Elena Guerra-Baamonde, Jorge González-Ramírez, Manuel Vázquez-Caruncho, Abdul W. Basit, Alvaro Goyanes, Visualizing disintegration of 3D printed tablets in humans using MRI and comparison with in vitro data, Journal of Controlled Release, Volume 365, 2024, Pages 348-357, ISSN 0168-3659, https://doi.org/10.1016/j.jconrel.2023.11.022.

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