AAPS PharmSciTech

, 20:310 | Cite as

Preparation of Filaments and the 3D Printing of Dronedarone HCl Tablets for Treating Cardiac Arrhythmias

  • Gordana MatijašićEmail author
  • Matija Gretić
  • Kristina Kezerić
  • Juraj Petanjek
  • Ema Vukelić
Research Article


The production of 3D-printed dosage forms requires the preparation of high-quality filaments containing an active pharmaceutical ingredient (API). The objective of this research is to prepare filaments containing dronedarone hydrochloride, a drug used in the treatment of cardiac arrhythmias. Filaments and 3D-printed tablets were subjected to characterization methods in order to prove and ensure the stability of the API and preservation of the drug content. Blends containing different proportions of dronedarone hydrochloride (DNR), polyethylene glycol (PEG), and polyvinyl alcohol filament (PVA) were prepared in two forms: as a powder mixture and as a solid dispersion. Thermogravimetric analysis was conducted, and the thermal properties of the components and polymer blends were tested using differential scanning calorimetry. Hot melt extrusion at 170 °C was used to prepare the filaments, and the fused deposition modeling technique was employed to print tablets. Drug release profiles were obtained by in vitro tests. The results indicate that the mixture containing 10 wt.% of polyethylene glycol prepared as a solid dispersion exhibits the most straightforward structure and shows only the slightest deviation from the target filament diameter. The compact structure of the tablet obtained from the filament provides a uniform in vitro drug release over a 24-h period. It also shows the smallest aberration from the expected DNR content in the tablet. The paper demonstrates that a blend containing 10 wt.% of PEG, 10 wt.% of DNR, and 80 wt.% of PVA filament is the most appropriate formula for extrusion and tablet printing.


filament fused deposition modeling (FDM) 3D printing dronedarone-hydrochloride hot melt extrusion 



active pharmaceutical ingredient


three-dimensional printing


computer aided design


dronedarone hydrochloride


differential scanning calorimetry


US Food and Drug Administration


fused deposition modeling


hot melt extrusion


melt flow rate


polyethylene glycol


polyvinyl alcohol


scanning electron microscopy


thermogravimetric analysis


X-ray diffraction



  1. 1.
    Mesko B. 12 things we can 3D print in medicine - 3D printing industry [Internet]. [cited 2019 Jan 23]. Available from:
  2. 2.
    Khaled SA, Burley JC, Alexander MR, Roberts CJ. Desktop 3D printing of controlled release pharmaceutical bilayer tablets. Int J Pharm. 2014;461(1–2):105–11.CrossRefGoogle Scholar
  3. 3.
    Goyanes A, Robles Martinez P, Basit AW. Effect of geometry on drug release from 3D printed tablets. Int J Pharm. 2015;494(2):657–63.CrossRefGoogle Scholar
  4. 4.
    Perissutti B, Newton JM, Podczeck F, Rubessa F. Preparation of extruded carbamazepine and PEG 4000 as a potential rapid release dosage form. Eur J Pharm Biopharm. 2002;53(1):125–32.CrossRefGoogle Scholar
  5. 5.
    Goyanes A, Buanz ABM, Hatton GB, Gaisford S, Basit AW. 3D printing of modified-release aminosalicylate (4-ASA and 5-ASA) tablets. Eur J Pharm Biopharm. 2015;89:157–62.CrossRefGoogle Scholar
  6. 6.
    Skowyra J, Pietrzak K, Alhnan MA. Fabrication of extended-release patient-tailored prednisolone tablets via fused deposition modelling (FDM) 3D printing. Eur J Pharm Sci. 2015;68:11–7.CrossRefGoogle Scholar
  7. 7.
    Lepowsky E, Tasoglu S. 3D printing for drug manufacturing: a perspective on the future of pharmaceuticals. Int J Bioprint. 2017;4(1):119.CrossRefGoogle Scholar
  8. 8.
    Kezerić K, Petanjek J, Poropat A, Gretić M Development of filament and 3D printing of tablets. In: Book of abstract SMLKI 2018. HDKI; 2018. p. 64.Google Scholar
  9. 9.
    EMEA. Dissolution test for solid dosage forms. In: European Pharmacopeia 86. 2016.Google Scholar
  10. 10.
    Dissolution Methods. [cited 2019 Jan 15]; Available from:
  11. 11.
    ISO 1133-1:2011, Plastics-determination of the melt mass-flow rate (MFR) and melt volume-flow rate (MVR) of thermoplastics. 2011.Google Scholar
  12. 12.
    Zhang Y, Huo M, Zhou J, Zou A, Li W, Yao C, et al. DDSolver: an add-in program for modeling and comparison of drug dissolution profiles. AAPS J. 2010;12:263–71.CrossRefGoogle Scholar
  13. 13.
    Shaikh HK, Kshirsagar RV, Patil SG. Mathematical models for drug release characterization: a review. World J Pharm Pharm Sci. 2014;4(4):324–38.Google Scholar
  14. 14.
    Suvakanta D, Narasimha MP, Lilakanta N, Prasanta C. Kinetic modeling on drug release from controlled drug delivery systems. Acta Pol Pharm Drug Res. 2010;67:217–23.Google Scholar
  15. 15.
  16. 16.
    Polyethylene glycol (PEG) [Internet]. [cited 2019 Jan 15]. Available from: GLYCOL.htm.
  17. 17.
    Polyethylene glycol 20000 CAS 25322–68-3 | 818897 [Internet]. [cited 2019 Jan 15]. Available from:,MDA_CHEM-818897
  18. 18.
    Iram F, Ali S, Ahmad A, Khan SA, Husain A. A review on dronedarone: pharmacological, pharmacodynamic and pharmacokinetic profile. J Acute Dis. 2016;5(2):102–8.CrossRefGoogle Scholar
  19. 19.
    Han SD, Jung SW, Jang SW, Jung HJ, Son M, Kim BM, Kang MJ Preparation of solid dispersion of dronedarone hydrochloride with Soluplus® by hot melt extrusion technique for enhanced drug release. Chem Pharm Bull (Tokyo) [Internet] 2015 [cited 2019 Jul 9];63(4):295–9. Available from: CrossRefGoogle Scholar
  20. 20.
    Ha E-S, Lee Y-R, Kim M-S. Solubility of dronedarone hydrochloride in six pure solvents at the range of 298.15 to 323.15 K. J Mol Liq [Internet]. 2016 Apr 1 [cited 2019 Jul 9];216:360–3. Available from:
  21. 21.
    Sanofi. Australian public assessment report for dronedarone hydrochloride. 2010.Google Scholar
  22. 22.
    Wu W, Tian H, Xiang A. Influence of polyol plasticizers on the properties of polyvinyl alcohol films fabricated by melt processing. J Polym Environ. 2012;20:63–9.CrossRefGoogle Scholar
  23. 23.
    Poly(vinyl alcohol) information and properties [Internet]. [cited 2019 Jan 15]. Available from:
  24. 24.
    Marcolino AIP, Macedo LB, Nogueira-Librelotto DR, Fernandes JR, Bender CR, Wust KM, et al. Preparation, characterization and in vitro cytotoxicity study of dronedarone hydrochloride inclusion complexes. Mater Sci Eng C. 2019;100:48–61.CrossRefGoogle Scholar
  25. 25.
    Holland BJ, Hay JN. The thermal degradation of poly (vinyl alcohol). Polymer. 2001;42:6775–83.CrossRefGoogle Scholar
  26. 26.
    Yang H, Xu S, Jiang L, Dan Y. Thermal decomposition behavior of poly (vinyl alcohol) with different hydroxyl content. Macromol Sci Part B Phys. 2012;51(3):464–80.CrossRefGoogle Scholar
  27. 27.
    Dimonie D, Musat M, Doncea SM, Damian CM, Anton L, Vasile E, et al. Controlling the melt resistance to flow as a possibility of improving the miscibility and the time behavior of some blends based on starch. Int J Polym Sci. 2015;2015:1–12.CrossRefGoogle Scholar
  28. 28.
    Dimonie D, Petrache M, Damian C, Anton L, Musat M, Dima Ş-O, et al. New evidences on the process sensitivity of some renewable blends based on starch considering their melt rheological properties. Int J Polym Sci. 2016;2016:1–10.CrossRefGoogle Scholar
  29. 29.
    Tooley MH. Design engineering manual. Butterworth-Heinemann; 2010.Google Scholar
  30. 30.
    Yeole BD, Patil RP, Lone KD, Tekade AR. Preparation of nanoparticles of poorly water soluble dronedarone by antisolvent addition technique using natural polymer as a stabilizer. J Pharm Res Clin Pract. 2016;6(4):8–16.Google Scholar
  31. 31.
    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(1–2):186–97.CrossRefGoogle Scholar
  32. 32.
    Gioumouxouzis CI, Katsamenis OL, Bouropoulos N, Fatouros DG. 3D printed oral solid dosage forms containing hydrochlorothiazide for controlled drug delivery. J Drug Delivery Sci Technol. 2017;40:164–71.CrossRefGoogle Scholar
  33. 33.
    Feng X, Ye X, Park JB, Lu W, Morott J, Beissner B, et al. Evaluation of the recrystallization kinetics of hot-melt extruded polymeric solid dispersions using an improved Avrami equation. Drug Dev Ind Pharm. 2015;41(9):1479–87.CrossRefGoogle Scholar
  34. 34.
    Medarević D, Ibrić S, Duriš J, Durić Z. Primena čvrstih disperzija u farmaceutskoj tehnologiji: Postupci izrade i metode karakterizacije. Arh Farm. 2013;63(6):473–93.Google Scholar
  35. 35.
    Chung CI. Extrusion of polymers theory & practice. 2nd Ed. Cincinnati: Hanser Publications; 2000.Google Scholar
  36. 36.
    Patel A, Sahu D, Dashora A, Garg R, Agraval P, Patel P, et al. A review of hot melt extrusion technique. Int J Innov Res Sci Eng Technol [Internet]. 2013 [cited 2019 Jul 11];2. Available from:
  37. 37.
    Maniruzzaman M, Boateng JS, Snowden MJ, Douroumis D. A review of hot-melt extrusion: process technology to pharmaceutical products. ISRN Pharm [Internet]. 2012 [cited 2019 Jul 11];2012:436763. Available from:
  38. 38.
    Frankland J. EXTRUSION: Better mix in means better mix out : plastics technology [Internet]. 2016 [cited 2019 Jan 15]. Available from:
  39. 39.
    Cardona C, Curdes AH, Isaacs AJ. Effects of filament diameter tolerances in fused filament fabrication. IUJUR 2016;II:2014–7.Google Scholar
  40. 40.
    Jafari M, Kaffashi B. Mathematical kinetic modeling on isoniazid release from Dex-HEMA-PNIPAAm nanogels. Nanomed Res J. 2016;1(2):90–6.Google Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2019

Authors and Affiliations

  1. 1.Faculty of Chemical Engineering and TechnologyUniversity of ZagrebZagrebCroatia
  2. 2.PLIVA Croatia Ltd.ZagrebCroatia

Personalised recommendations