Tailored on demand anti-coagulant dosing: An in vitro and in vivo evaluation of 3D printed purpose-designed oral dosage forms

Arafat, Basel and Qinna, Nidal and Cieszynska, Milena and Forbes, Robert T. and Alhnan, Mohamed A. (2018) Tailored on demand anti-coagulant dosing: An in vitro and in vivo evaluation of 3D printed purpose-designed oral dosage forms. European Journal of Pharmaceutics and Biopharmaceutics, 128. pp. 282-289. ISSN 1873-3441

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Official URL: https://doi.org/10.1016/j.ejpb.2018.04.010


Coumarin therapy has been associated with high levels of inter- and intra-individual variation in the required dose to reach a therapeutic anticoagulation outcome. Therefore, a dynamic system that is able to achieve accurate delivery of a warfarin dose is of significant importance. Here we assess the ability of 3D printing to fabricate and deliver tailored individualised precision dosing using in-vitro and in-vivo models. Sodium warfarin loaded filaments were compounded using hot melt extrusion (HME) and further fabricated via fused deposition modelling (FDM) 3D printing to produce capsular-ovoid-shaped dosage forms loaded at 200 or 400 µg dose. The solid dosage forms and comparator warfarin aqueous solutions were administered by oral gavage to Sprague–Dawley rats. A novel UV imaging approach indicated that the erosion of the methacrylate matrix was at a rate of 16.4 and 15.2 µm/min for horizontal and vertical planes respectively. In vivo, 3D printed forms were as proportionately effective as their comparative solution form in doubling plasma exposure following a doubling of warfarin dose (184% versus 192% respectively). The 3D printed ovoids showed a lower Cmax of warfarin (1.51 and 3.33 mg/mL versus 2.5 and 6.44 mg/mL) and a longer Tmax (6 and 3.7 versus 4 and 1.5 h) in comparison to liquid formulation. This work demonstrates for the first time in vivo, the potential of FDM 3D printing to produce a tailored specific dosage form and to accurately titrate coumarin dose response to an individual patient.

Item Type: Journal Article
Keywords: Rapid prototyping, Patient-centred, Personalized, Patient-specific, Three dimensional printing, Additive manufacturing
Faculty: ARCHIVED Faculty of Medical Science (until September 2018)
Depositing User: Lisa Blanshard
Date Deposited: 31 Aug 2018 09:31
Last Modified: 09 Sep 2021 16:10
URI: https://arro.anglia.ac.uk/id/eprint/703528

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