Virtual Prototyping and Parametric Design of 3D-Printed Tablets Based on the Solution of Inverse Problem

Abstract

The problem of designing tablet geometry and its internal structure that results into a specified release profile of the drug during dissolution was considered. A solution method based on parametric programming, inspired by CAD (computer-aided design) approaches currently used in other fields of engineering, was proposed and demonstrated. The solution of the forward problem using a parametric series of structural motifs was first carried out in order to generate a library of drug release profiles associated with each structural motif. The inverse problem was then solved in three steps: first, the combination of basic structural motifs whose superposition provides the closest approximation of the required drug release profile was found by a linear combination of pre-calculated release profiles. In the next step, the final tablet design was constructed and its dissolution curve found computationally. Finally, the proposed design was 3D printed and its dissolution profile was confirmed experimentally. The computational method was based on the numerical solution of drug diffusion in a boundary layer surrounding the tablet, coupled with erosion of the tablet structure encoded by the phase volume function. The tablets were 3D printed by fused deposition modelling (FDM) from filaments produced by hot-melt extrusion. It was found that the drug release profile could be effectively controlled by modifying the tablet porosity. Custom release profiles were obtained by combining multiple porosity regions in the same tablet. The computational method yielded accurate predictions of the drug release rate for both single- and multi-porosity tablets.

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References

  1. 1.

    Meyer UA, Zanger UM, Schwab M. Omics and drug response. Annu Rev Pharmacol Toxicol. 2013;53:475–502.

    CAS  Article  Google Scholar 

  2. 2.

    Momper JD, Wagner JA. Therapeutic drug monitoring as a component of personalized medicine: applications in pediatric drug development. Clin Pharmacol Ther. 2014;95:138–40.

    CAS  Article  Google Scholar 

  3. 3.

    Koudijs KKM, Moes DJ, Hartigh J. Interfacing MW\Pharm to a laboratory information system calculates AUCs of immunosuppressants with fewer errors and in less time. Pharm Weekbl. 2015;150:250–2.

    Google Scholar 

  4. 4.

    Khaled SA, Burley JC, Alexander MR, Yang J, Roberts CJ. 3D printing of five-in-one dose combination polypill with defined immediate and sustained release profiles. J Control Release. 2015;217:308–14.

    CAS  Article  Google Scholar 

  5. 5.

    Khaled SA, Burley JC, Alexander MR, Yang J, Roberts CJ. 3D printing of tablets containing multiple drugs with defined release profiles. Int J Pharm. 2015;494:643–50.

    CAS  Article  Google Scholar 

  6. 6.

    Martinez PR, Goyanes A, Basit AW, Gaisford S. Fabrication of drug-loaded hydrogels with stereolithographic 3D printing. Int J Pharm. 2017;532:313–7.

    CAS  Article  Google Scholar 

  7. 7.

    Kyobula M, Adedeji A, Alexander MR, Saleh E, Wildman R, Ashcroft I, et al. 3D inkjet printing of tablets exploiting bespoke complex geometries for controlled and tuneable drug release. J Control Release. 2017;261:207–15.

    CAS  Article  Google Scholar 

  8. 8.

    Goyanes A, Robles Martinez P, Buanz A, Basit AW, Gaisford S. Effect of geometry on drug release from 3D printed tablets. Int J Pharm. 2015;494:657–63.

    CAS  Article  Google Scholar 

  9. 9.

    Zhang J, Yang W, Vo AQ, Feng X, Ye X, Kim DW, et al. Hydroxypropyl methylcellulose-based controlled release dosage by melt extrusion and 3D printing: structure and drug release correlation. Carbohydr Polym. 2017;177:49–57.

    CAS  Article  Google Scholar 

  10. 10.

    Sadia M, Arafat B, Ahmed W, Forbes RT, Alhnan MA. Channelled tablets: an innovative approach to accelerating drug release from 3D printed tablets. J Control Release. 2018;269:355–63.

    CAS  Article  Google Scholar 

  11. 11.

    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;33:2704–12.

    CAS  Article  Google Scholar 

  12. 12.

    Sadia M, Sośnicka A, Arafat B, Isreb A, Ahmed W, Kelarakis A, et al. Adaptation of pharmaceutical excipients to FDM 3D printing for the fabrication of patient-tailored immediate release tablets. Int J Pharm. 2016;513:659–68.

    CAS  Article  Google Scholar 

  13. 13.

    Goyanes A, Scarpa M, Kamlow M, Gaisford S, Basit AW, Orlu M. Patient acceptability of 3D printed medicines. Int J Pharm. 2017;530:71–8.

    CAS  Article  Google Scholar 

  14. 14.

    Tanaka M. Inverse problems in engineering mechanics IV. International symposium on inverse problems in engineering mechanics 2003. Nagano: Elsevier; 2003.

    Google Scholar 

  15. 15.

    Malone JB, Vadyak J, Sankar LN. Inverse aerodynamic design method for aircraft components. J Aircr. 1987;24:8–9.

    Article  Google Scholar 

  16. 16.

    Matsushima K, Iwamiya T. An aerodynamic design method for multi-element wings using inverse problems A2. In: Tanaka M, Dulikravich GS, editors. Inverse problems in engineering mechanics. Oxford: Elsevier Science Ltd; 1998. p. 417–25.

    Google Scholar 

  17. 17.

    Leifsson L, Koziel S. Multi-fidelity design optimization of transonic airfoils using physics-based surrogate modeling and shape-preserving response prediction. Journal of Computational Science. 2010;1:98–106.

    Article  Google Scholar 

  18. 18.

    Woodbury KA. Inverse Engineering Handbook. Boca Raton: CRC press; 2002.

    Google Scholar 

  19. 19.

    Štěpánek F. Computer-aided product design: Granule dissolution. Chem Eng Res Des. 2004;82:1458–66.

    Article  Google Scholar 

  20. 20.

    Kimber JA, Kazarian SG, Štěpánek F. DEM simulation of drug release from structurally heterogeneous swelling tablets. Powder Technol. 2013;248:68–76.

    CAS  Article  Google Scholar 

  21. 21.

    Zhang J, Feng X, Patil H, Tiwari RV, Repka MA. Coupling 3D printing with hot-melt extrusion to produce controlled-release tablets. Int J Pharm. 2017;519:186–97.

    CAS  Article  Google Scholar 

  22. 22.

    Chai X, Chai H, Wang X, Yang J, Li J, Zhao Y, et al. Fused deposition modeling (FDM) 3D printed tablets for intragastric floating delivery of domperidone. Sci Rep. 2017;7:2829.

    Article  Google Scholar 

  23. 23.

    Korte C, Quodbach J. 3D-printed network structures as controlled-release drug delivery systems: dose adjustment, API release analysis and prediction. AAPS PharmSciTech. 2018, accepted. https://doi.org/10.1208/s12249-018-1017-0.

    CAS  Article  Google Scholar 

  24. 24.

    Norman J, Madurawe RD, Moore CMV, Khan MA, Khairuzzaman A. A new chapter in pharmaceutical manufacturing: 3D-printed drug products. Adv Drug Deliv Rev. 2017;108:39–50.

    CAS  Article  Google Scholar 

  25. 25.

    Palo M, Holländer J, Suominen J, Yliruusi J, Sandler N. 3D printed drug delivery devices: perspectives and technical challenges. Expert Rev Med Devices. 2017;14:685–96.

    CAS  Article  Google Scholar 

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Funding

The authors would like to thank Zentiva, k.s., for supporting this work. M.N. ant T.B. would like to acknowledge financial support by Specific University Research (MSMT 21-SVV/2018).

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Correspondence to František Štěpánek.

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Guest Editors: Niklas Sandler and Jukka Rantanen

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Novák, M., Boleslavská, T., Grof, Z. et al. Virtual Prototyping and Parametric Design of 3D-Printed Tablets Based on the Solution of Inverse Problem. AAPS PharmSciTech 19, 3414–3424 (2018). https://doi.org/10.1208/s12249-018-1176-z

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KEY WORDS

  • 3D printing
  • hot-melt extrusion
  • parametric programming
  • dissolution
  • mathematical modelling