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      3D printing by fused deposition modeling (FDM) of a swellable/erodible capsular device for oral pulsatile release of drugs

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      Publication date Created:
      Publication date (Print):
      Journal: Journal of Drug Delivery Science and Technology
      Publisher: Elsevier BV

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          Effect of geometry on drug release from 3D printed tablets

          Alvaro Goyanes, Pamela Robles Martinez, Asma B.M. Buanz … (2015)
          The aim of this work was to explore the feasibility of combining hot melt extrusion (HME) with 3D printing (3DP) technology, with a view to producing different shaped tablets which would be otherwise difficult to produce using traditional methods. A filament extruder was used to obtain approx. 4% paracetamol loaded filaments of polyvinyl alcohol with characteristics suitable for use in fused-deposition modelling 3DP. Five different tablet geometries were successfully 3D-printed-cube, pyramid, cylinder, sphere and torus. The printing process did not affect the stability of the drug. Drug release from the tablets was not dependent on the surface area but instead on surface area to volume ratio, indicating the influence that geometrical shape has on drug release. An erosion-mediated process controlled drug release. This work has demonstrated the potential of 3DP to manufacture tablet shapes of different geometries, many of which would be challenging to manufacture by powder compaction.
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            3D printing of modified-release aminosalicylate (4-ASA and 5-ASA) tablets

            Alvaro Goyanes, Asma B.M. Buanz, Grace B. Hatton … (2015)
            The aim of this study was to explore the potential of fused-deposition 3-dimensional printing (FDM 3DP) to produce modified-release drug loaded tablets. Two aminosalicylate isomers used in the treatment of inflammatory bowel disease (IBD), 5-aminosalicylic acid (5-ASA, mesalazine) and 4-aminosalicylic acid (4-ASA), were selected as model drugs. Commercially produced polyvinyl alcohol (PVA) filaments were loaded with the drugs in an ethanolic drug solution. A final drug-loading of 0.06% w/w and 0.25% w/w was achieved for the 5-ASA and 4-ASA strands, respectively. 10.5mm diameter tablets of both PVA/4-ASA and PVA/5-ASA were subsequently printed using an FDM 3D printer, and varying the weight and densities of the printed tablets was achieved by selecting the infill percentage in the printer software. The tablets were mechanically strong, and the FDM 3D printing was shown to be an effective process for the manufacture of the drug, 5-ASA. Significant thermal degradation of the active 4-ASA (50%) occurred during printing, however, indicating that the method may not be appropriate for drugs when printing at high temperatures exceeding those of the degradation point. Differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) of the formulated blends confirmed these findings while highlighting the potential of thermal analytical techniques to anticipate drug degradation issues in the 3D printing process. The results of the dissolution tests conducted in modified Hank's bicarbonate buffer showed that release profiles for both drugs were dependent on both the drug itself and on the infill percentage of the tablet. Our work here demonstrates the potential role of FDM 3DP as an efficient and low-cost alternative method of manufacturing individually tailored oral drug dosage, and also for production of modified-release formulations.
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              Fabrication of extended-release patient-tailored prednisolone tablets via fused deposition modelling (FDM) 3D printing.

              Mohamed Alhnan, Katarzyna Pietrzak, Justyna Skowyra (2015)
              Rapid and reliable tailoring of the dose of controlled release tablets to suit an individual patient is a major challenge for personalized medicine. The aim of this work was to investigate the feasibility of using a fused deposition modelling (FDM) based 3D printer to fabricate extended release tablet using prednisolone loaded poly(vinyl alcohol) (PVA) filaments and to control its dose. Prednisolone was loaded into a PVA-based (1.75 mm) filament at approximately 1.9% w/w via incubation in a saturated methanolic solution of prednisolone. The physical form of the drug was assessed using differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD). Dose accuracy and in vitro drug release patterns were assessed using HPLC and pH change flow-through dissolution test. Prednisolone loaded PVA filament demonstrated an ability to be fabricated into regular ellipse-shaped solid tablets using the FDM-based 3D printer. It was possible to control the mass of printed tablet through manipulating the volume of the design (R(2) = 0.9983). On printing tablets with target drug contents of 2, 3, 4, 5, 7.5 and 10mg, a good correlation between target and achieved dose was obtained (R(2) = 0.9904) with a dose accuracy range of 88.7-107%. Thermal analysis and XRPD indicated that the majority of prednisolone existed in amorphous form within the tablets. In vitro drug release from 3D printed tablets was extended up to 24h. FDM based 3D printing is a promising method to produce and control the dose of extended release tablets, providing a highly adjustable, affordable, minimally sized, digitally controlled platform for producing patient-tailored medicines.
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                Author and article information

                Journal
                Title: Journal of Drug Delivery Science and Technology
                Abbreviated Title: Journal of Drug Delivery Science and Technology
                Publisher: Elsevier BV
                ISSN (Print): 17732247
                Publication date Created: December 2015
                Publication date (Print): December 2015
                Volume: 30
                Issue:
                Pages: 360-367
                Article
                DOI: 10.1016/j.jddst.2015.07.016
                SO-VID: 70f11956-013f-4d68-827c-a8dda61fd146
                Copyright © © 2015
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