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

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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

References

  1. Raijada D, Genina N, Fors D, Wisaeus E, Peltonen J, Rantanen J, et al. A step toward development of printable dosage forms for poorly soluble drugs. J Pharm Sci. 2013;102(10):3694–704.

    Article  CAS  PubMed  Google Scholar 

  2. Habib WA, Alanizi AS, Abdelhamid MM, Alanizi FK. Accuracy of tablet splitting: comparison study between hand splitting and tablet cutter. Saudi Pharm J. 2014;22(5):454–9.

    Article  PubMed  Google Scholar 

  3. Peek BT, Al-Achi A, Coombs SJ. Accuracy of tablet splitting by elderly patients. JAMA. 2002;288(4):451–2.

    Article  PubMed  Google Scholar 

  4. Noviasky J, Lo V, Luft DD, Saseen J. Clinical inquiries. Which medications can be split without compromising efficacy and safety? J Fam Pract. 2006;55(8):707–8.

    PubMed  Google Scholar 

  5. Skowyra J, Pietrzak K, Alhnan MA. Fabrication of extended-release patient-tailored prednisolone tablets via fused deposition modelling (FDM) 3D printing. Eur J Pharmaceut Sci. 2015;68:11–7.

    Article  CAS  Google Scholar 

  6. Alhnan MA, Okwuosa TC, Sadia M, Wan KW, Ahmed W, Arafat B. Emergence of 3D printed dosage forms: opportunities and challenges. Pharm Res. 2016;33(8):1817–32.

    Article  CAS  PubMed  Google Scholar 

  7. Nollenberger K, Albers J. Poly(meth)acrylate-based coatings. Int J Pharm. 2013;457(2):461–9.

    Article  CAS  PubMed  Google Scholar 

  8. Sakae O, Hiroyasu K. Application of HPMC and HPMCAS to aqueous film coating of pharmaceutical dosage forms. In: McGinity JW, Felton LA, editors. Aqueous film coating of pharmaceutical dosage forms. Boca Raton: CRC Press; 2008.

    Google Scholar 

  9. Revision USPCCo. U.S. pharmacopeia & national formulary: United States Pharmacopeial Convention, Inc.; 2007.

  10. Katstra WE, Palazzolo RD, Rowe CW, Giritlioglu B, Teung P, Cima MJ. Oral dosage forms fabricated by Three Dimensional Printing™. J Control Release. 2000;66(1):1–9.

    Article  CAS  PubMed  Google Scholar 

  11. Rowe CW, Katstra WE, Palazzolo RD, Giritlioglu B, Teung P, Cima MJ. Multimechanism oral dosage forms fabricated by three dimensional printing (TM). J Control Release. 2000;66(1):11–7.

    Article  CAS  PubMed  Google Scholar 

  12. Yu DG, Yang XL, Huang WD, Liu J, Wang YG, Xu H. Tablets with material gradients fabricated by three-dimensional printing. J Pharm Sci. 2007;96(9):2446–56.

    Article  CAS  PubMed  Google Scholar 

  13. Rowe CW, Wang CC, Monkhouse DC. TheriForm technology. In: Rathbone MJ, Hadgraft J, Roberts MS, editors. Modified-release drug delivery technology. 2nd ed. New York: Marcel Dekker Inc; 2003. p. 77–8.

    Google Scholar 

  14. Goyanes A, Buanz AB, Hatton GB, Gaisford S, Basit AW. 3D printing of modified-release aminosalicylate (4-ASA and 5-ASA) tablets. Eur J Pharmaceut Biopharmaceut: Off J Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik eV. 2014.

  15. Goyanes A, Buanz ABM, Basit AW, Gaisford S. Fused-filament 3D printing (3DP) for fabrication of tablets. Int J Pharm. 2014;476(1–2):88–92.

    Article  CAS  PubMed  Google Scholar 

  16. Sandler N, Salmela I, Fallarero A, Rosling A, Khajeheian M, Kolakovic R, et al. Towards fabrication of 3D printed medical devices to prevent biofilm formation. Int J Pharm. 2014;459(1–2):62–4.

    Article  CAS  PubMed  Google Scholar 

  17. Pietrzak K, Isreb A, Alhnan MA. A flexible-dose dispenser for immediate and extended release 3D printed tablets. Eur J Pharmaceut Biopharmaceut: Off J Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik eV. 2015.

  18. Okwuosa TC, Stefaniak D, Arafat B, Isreb A, Wan KW, Alhnan MA. A lower temperature FDM 3D printing for the manufacture of patient-specific immediate release tablets. Pharm Res. 2016.

  19. Sadia M, Sosnicka A, Arafat B, Isreb A, Ahmed W, Kelarakis A, Alhnan MA. Adaptation of pharmaceutical excipients to FDM 3D printing for the fabrication of patient-tailored immediate release tablets. Int J Pharmaceut. 2016.

  20. Goyanes A, Chang H, Sedough D, Hatton GB, Wang J, Buanz A, et al. Fabrication of controlled-release budesonide tablets via desktop (FDM) 3D printing. Int J Pharm. 2015;496(2):414–20.

    Article  CAS  PubMed  Google Scholar 

  21. Melocchi A, Parietti F, Maroni A, Foppoli A, Gazzaniga A, Zema L. Hot-melt extruded filaments based on pharmaceutical grade polymers for 3D printing by fused deposition modeling. Int J Pharm. 2016;509(1–2):255–63.

    Article  CAS  PubMed  Google Scholar 

  22. Hergel J, Lefebvre S. Clean color: improving multi-filament 3D prints. Comput Graphics Forum. 2014;33(2):469–78.

    Article  Google Scholar 

  23. Reiner T, Carr N. Radom, #237, M r, #283, ch, Ond, #345, ej, #352, t’ava, Dachsbacher C, Miller G. Dual-color mixing for fused deposition modeling printers. Comput Graphics Forum. 2014;33(2):479–86.

    Article  Google Scholar 

  24. Dudek P. FDM 3D printing technology in manufacturing composite elements. In.Archives of Metallurgy and Materials; 2013. p. 1415.

  25. Goyanes A, Wang J, Buanz A, Martinez-Pacheco R, Telford R, Gaisford S, et al. 3D printing of medicines: engineering novel oral devices with unique design and drug release characteristics. Mol Pharm. 2015;12(11):4077–84.

    Article  CAS  PubMed  Google Scholar 

  26. Yu DG, Williams GR, Wang X, Liu XK, Li HL, Bligh SWA. Dual drug release nanocomposites prepared using a combination of electrospraying and electrospinning. RSC Adv. 2013;3(14):4652–8.

    Article  CAS  Google Scholar 

  27. Yang C, Yu DG, Pan D, Liu XK, Wang X, Bligh SWA, et al. Electrospun pH-sensitive core shell polymer nanocomposites fabricated using a tri-axial process. Acta Biomater. 2016;35:77–86.

    Article  PubMed  Google Scholar 

  28. Fadda HM, Basit AW. Dissolution of pH responsive formulations in media resembling intestinal fluids: bicarbonate versus phosphate buffers. J Drug Deliv Sci Technol. 2005;15(4):273–9.

    Article  CAS  Google Scholar 

  29. Alhnan MA, Cosi D, Murdan S, Basit AW. Inhibiting the gastric burst release of drugs from enteric microparticles: the influence of drug molecular mass and solubility. J Pharm Sci. 2010;99(11):4576–83.

    Article  CAS  PubMed  Google Scholar 

  30. Hao S, Wang B, Wang Y, Zhu L, Wang B, Guo T. Preparation of Eudragit L 100–55 enteric nanoparticles by a novel emulsion diffusion method. Colloids Surf B: Biointerfaces. 2013;108:127–33.

    Article  CAS  PubMed  Google Scholar 

  31. Thoma K, Bechtold K. Influence of aqueous coatings on the stability of enteric coated pellets and tablets. Eur J Pharm Biopharm. 1999;47(1):39–50.

    Article  CAS  PubMed  Google Scholar 

  32. Liu F, Lizio R, Meier C, Petereit HU, Blakey P, Basit AW. A novel concept in enteric coating: a double-coating system providing rapid drug release in the proximal small intestine. J Control Release. 2009;133(2):119–24.

    Article  CAS  PubMed  Google Scholar 

  33. Tudja P, Khan MZ, Mestrovic E, Horvat M, Golja P. Thermal behaviour of diclofenac sodium: decomposition and melting characteristics. Chem Pharm Bull (Tokyo). 2001;49(10):1245–50.

    Article  CAS  Google Scholar 

  34. Verdonck E, Schaap K, Thomas LC. A discussion of the principles and applications of Modulated Temperature DSC (MTDSC). Int J Pharm. 1999;192(1):3–20.

    Article  CAS  PubMed  Google Scholar 

  35. Nair R, Nyamweya N, Gönen S, Martínez-Miranda LJ, Hoag SW. Influence of various drugs on the glass transition temperature of poly(vinylpyrrolidone): a thermodynamic and spectroscopic investigation. Int J Pharm. 2001;225(1–2):83–96.

    Article  CAS  PubMed  Google Scholar 

  36. Kim JE, Cho HJ, Kim DD. Budesonide/cyclodextrin complex-loaded lyophilized microparticles for intranasal application. Drug Dev Ind Pharm. 2014;40(6):743–8.

    Article  CAS  PubMed  Google Scholar 

  37. Toropainen T, Velaga S, Heikkila T, Matilainen L, Jarho P, Carlfors J, et al. Preparation of budesonide/gamma-cyclodextrin complexes in supercritical fluids with a novel SEDS method. J Pharm Sci. 2006;95(10):2235–45.

    Article  CAS  PubMed  Google Scholar 

  38. Korkiatithaweechai S, Umsarika P, Praphairaksit N, Muangsin N. Controlled release of diclofenac from matrix polymer of chitosan and oxidized konjac glucomannan. Mar Drugs. 2011;9(9):1649–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Liu F, Merchant HA, Kulkarni RP, Alkademi M, Basit AW. Evolution of a physiological pH 6.8 bicarbonate buffer system: application to the dissolution testing of enteric coated products. Eur J Pharmaceut Biopharmaceut: Off J Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik eV. 2011;78(1):151–7.

    Article  CAS  Google Scholar 

  40. Ming-Thau S, Huei-Lan C, Ching-Cheng K, Cheng-Hsiung L, Sokoloski TD. Dissolution of diclofenac sodium from matrix tablets. Int J Pharm. 1992;85(1):57–63.

    Article  Google Scholar 

  41. Bhatt H, Naik B, Dharamsi A. Solubility enhancement of budesonide and statistical optimization of coating variables for targeted drug delivery. J Pharmaceut. 2014;2014:13.

    Google Scholar 

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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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Authors and Affiliations

  1. School of Pharmacy and Biomedical Sciences, University of Central Lancashire, Preston, Lancashire, UK

    Tochukwu C. Okwuosa, Beatriz C. Pereira, Basel Arafat, Milena Cieszynska, Abdullah Isreb & Mohamed A. Alhnan

Authors
  1. Tochukwu C. Okwuosa
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  2. Beatriz C. Pereira
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  3. Basel Arafat
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  4. Milena Cieszynska
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  5. Abdullah Isreb
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  6. Mohamed A. Alhnan
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Corresponding author

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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  • DOI: https://doi.org/10.1007/s11095-016-2073-3

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