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Fabricating a Shell-Core Delayed Release Tablet Using Dual FDM 3D Printing for Patient-Centred Therapy

Abstract

Purpose

Individualizing gastric-resistant tablets is associated with major challenges for clinical staff in hospitals and healthcare centres. This work aims to fabricate gastric-resistant 3D printed tablets using dual FDM 3D printing.

Methods

The gastric-resistant tablets were engineered by employing a range of shell-core designs using polyvinylpyrrolidone (PVP) and methacrylic acid co-polymer for core and shell structures respectively. Filaments for both core and shell were compounded using a twin-screw hot-melt extruder (HME). CAD software was utilized to design a capsule-shaped core with a complementary shell of increasing thicknesses (0.17, 0.35, 0.52, 0.70 or 0.87 mm). The physical form of the drug and its integrity following an FDM 3D printing were assessed using x-ray powder diffractometry (XRPD), thermal analysis and HPLC.

Results

A shell thickness ≥0.52 mm was deemed necessary in order to achieve sufficient core protection in the acid medium. The technology proved viable for incorporating different drug candidates; theophylline, budesonide and diclofenac sodium. XRPD indicated the presence of theophylline crystals whilst budesonide and diclofenac sodium remained amorphous in the PVP matrix of the filaments and 3D printed tablets. Fabricated tablets demonstrated gastric resistant properties and a pH responsive drug release pattern in both phosphate and bicarbonate buffers.

Conclusions

Despite its relatively limited resolution, FDM 3D printing proved to be a suitable platform for a single-process fabrication of delayed release tablets. This work reveals the potential of dual FDM 3D printing as a unique platform for personalising delayed release tablets to suit an individual patient’s needs.

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Abbreviations

API:

Active pharmaceutical ingredient

CAD:

Computer aided design

DSC:

Differential scanning calorimetry

FDM:

Fused Deposition Modelling

HME:

Hot melt extrusion

HPLC:

High performance liquid chromatography

MTDSC:

Modulated temperature differential scanning calorimetry

PEG:

Polyethylene glycol

PVP:

Polyvinylpyrrolidone

SEM:

Scanning electron microscopy

TBP:

Tribasic sodium phosphate

TEC:

Triethyl citrate

Tg:

Glass transition temperature

TGA:

Thermal gravimetric analysis

Tm:

Melting point

XRPD:

X-ray powder diffractometry

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ACKNOWLEDGMENTS AND DISCLOSURES

The authors would like to thank UCLAN Innovation Team for their support and Mrs Rim Arafat for her help with graphics design.

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Correspondence to Mohamed A. Alhnan.

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Okwuosa, T.C., Pereira, B.C., Arafat, B. et al. Fabricating a Shell-Core Delayed Release Tablet Using Dual FDM 3D Printing for Patient-Centred Therapy. Pharm Res 34, 427–437 (2017). https://doi.org/10.1007/s11095-016-2073-3

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KEY WORDS

  • additive manufacturing
  • delayed release
  • gastric resistant
  • modified-release
  • patient-specific
  • personalised