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AAPS PharmSciTech

, Volume 19, Issue 8, pp 3362–3375 | Cite as

Controlled Release of 5-Fluorouracil from Alginate Beads Encapsulated in 3D Printed pH-Responsive Solid Dosage Forms

  • Christos I. Gioumouxouzis
  • Aikaterini-Theodora Chatzitaki
  • Christina Karavasili
  • Orestis L. Katsamenis
  • Dimitrios Tzetzis
  • Emmanouela Mystiridou
  • Nikolaos Bouropoulos
  • Dimitrios G. Fatouros
Research Article Theme: Printing and Additive Manufacturing
  • 349 Downloads
Part of the following topical collections:
  1. Theme: Printing and Additive Manufacturing

Abstract

Three-dimensional printing is being steadily deployed as manufacturing technology for the development of personalized pharmaceutical dosage forms. In the present study, we developed a hollow pH-responsive 3D printed tablet encapsulating drug loaded non-coated and chitosan-coated alginate beads for the targeted colonic delivery of 5-fluorouracil (5-FU). A mixture of Eudragit® L100-55 and Eudragit® S100 was fabricated by means of hot-melt extrusion (HME) and the produced filaments were printed utilizing a fused deposition modeling (FDM) 3D printer to form the pH-responsive layer of the tablet with the rest comprising of a water-insoluble poly-lactic acid (PLA) layer. The filaments and alginate particles were characterized for their physicochemical properties (thermogravimetric analysis, differential scanning calorimetry, X-ray diffraction), their surface topography was visualized by scanning electron microscopy and the filaments’ mechanical properties were assessed by instrumented indentation testing and tensile testing. The optimized filament formulation was 3D printed and the structural integrity of the hollow tablet in increasing pH media (pH 1.2 to pH 7.4) was assessed by means of time-lapsed microfocus computed tomography (μCT). In vitro release studies demonstrated controlled release of 5-FU from the alginate beads encapsulated within the hollow pH-sensitive tablet matrix at pH values corresponding to the colonic environment (pH 7.4). The present study highlights the potential of additive manufacturing in fabricating controlled-release dosage forms rendering them pertinent formulations for further in vivo evaluation.

KEY WORDS

three-dimensional printing microfocus computed tomography colonic delivery alginate beads 5-FU 

Notes

Acknowledgements

The authors would like to acknowledge μ-VIS X-Ray Imaging Centre and the Biomedical Imaging Unit at the University of Southampton for provision of tomographic imaging facilities, as well as Nikon Metrology UK Ltd for the provision of the Med-X prototype scanner.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

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Copyright information

© American Association of Pharmaceutical Scientists 2018

Authors and Affiliations

  • Christos I. Gioumouxouzis
    • 1
  • Aikaterini-Theodora Chatzitaki
    • 1
  • Christina Karavasili
    • 1
  • Orestis L. Katsamenis
    • 2
  • Dimitrios Tzetzis
    • 3
  • Emmanouela Mystiridou
    • 4
    • 5
  • Nikolaos Bouropoulos
    • 4
    • 5
  • Dimitrios G. Fatouros
    • 1
  1. 1.Laboratory of Pharmaceutical Technology, School of PharmacyAristotle University of ThessalonikiThessalonikiGreece
  2. 2.μ-VIS X-Ray Imaging Centre, Faculty of Engineering and the EnvironmentUniversity of SouthamptonSouthamptonUK
  3. 3.School of Science and TechnologyInternational Hellenic UniversityThermiGreece
  4. 4.Foundation for Research and Technology HellasInstitute of Chemical Engineering and High Temperature Chemical ProcessesPatrasGreece
  5. 5.Department of Materials ScienceUniversity of PatrasRioGreece

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