Tailored on demand anti-coagulant dosing: An in vitro and in vivo evaluation of 3D printed purpose-designed oral dosage forms
| Autor: | Robert Thomas Forbes, Mohamed Albed Alhnan, Milena Cieszynska, Nidal A. Qinna, Basel Arafat |
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| Rok vydání: | 2018 |
| Předmět: |
Male
Drug Compounding Cmax Administration Oral Pharmaceutical Science 02 engineering and technology 030226 pharmacology & pharmacy Dosage form Rats Sprague-Dawley Matrix (chemical analysis) 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine In vivo medicine Animals Dosing Dose-Response Relationship Drug Chemistry Warfarin Sodium B230 Warfarin Anticoagulants General Medicine 021001 nanoscience & nanotechnology Coumarin Rats Drug Liberation Models Animal Printing Three-Dimensional 0210 nano-technology Tablets Biotechnology medicine.drug Biomedical engineering |
| Zdroj: | European Journal of Pharmaceutics and Biopharmaceutics. 128:282-289 |
| ISSN: | 0939-6411 |
| DOI: | 10.1016/j.ejpb.2018.04.010 |
| Popis: | 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 an in-vitro model. 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 and 400 µg dose. The solid dosage forms and comparator warfarin aqueous solutions were administered by oral gavage to Sprague-Dawley rats. In vitro, warfarin release was faster at pH 1.2 in comparison to pH 2. 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 C of warfarin (1.51 and 3.33 mg/mL versus 2.5 and 6.44 mg/mL) and a longer T (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. [Abstract copyright: Copyright © 2018. Published by Elsevier B.V.] |
| Databáze: | OpenAIRE |
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