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

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.

X‐ray microfocus computed tomography: a powerful tool for structural and functional characterisation of 3D printed dosage forms

“…Fusion between layers can be suboptimal, resulting in unwanted internal pores, whereas variability in feedstock material rheology can lead to inconsistent extrusion patterns and material agglomerations. All these can have a compounding effect on the geometrical inaccuracy of the printed object (Gioumouxouzis et al ., ,b).…”

“…We would like to acknowledge μ‐VIS X‐Ray Imaging Centre at the University of Southampton for the provision of tomographic imaging facilities, as well as Nikon X‐Tek Systems Ltd for the provision of the Med‐X prototype scanner used in Gioumouxouzis et al . (2018b).…”

“…dissolution, hydration etc.) can be performed in situ or ex situ during µCT imaging, providing valuable insights of the behaviour of the structure and its constituent component over-time (Gioumouxouzis et al, 2017;Gioumouxouzis et al, 2018b) Figure 2. Such an approach is beneficial for accessing the dissolution behaviour of the 3D printed dosage forms.…”

Design and Fabrication of Three-Dimensional Printed Scaffolds for Cancer Precision Medicine

“…The 3DP has been used to develop DDS aiming for better targeting potential and less adverse side effects. [21][22][23] Standard Terminology for Additive Manufacturing Technologies categorized the 3DP processes into seven groups: material jetting, binder jetting, sheet lamination, directed energy deposition, material extrusion, powder bed fusion, and vat polymerization. 24 Among these methods, material jetting, fused deposition modeling (FDM), selective laser sintering, stereolithography (SLA), direct-write, and bioprinting have been widely used in medical and biomedical studies.…”

“…32 5-Fluorouracil (5FU) is an antineoplastic agent that has been used to treat several types of cancers, including breast, skin, stomach, bowel, and pancreatic cancer. 22 To achieve a targeted drug delivery to the colonic environment, a hollow pH-responsive 3D-printed tablet encapsulating 5FU was fabricated using FDM. 22 In vitro evaluations showed the targeted release of 5FU in pH 7.4, corresponding to the colonic environment.…”