Thermal Extrusion 3D Printing for the Fabrication of Puerarin Immediate-Release Tablets


Thermal extrusion (TE) 3D printing is a thermoplastic semisolid-based rapid prototyping process, which is capable of building complex structures. The aim of this study was to manufacture rapid-release puerarin tablets without solvent through TE 3D printing. Novel rapid-release tablets were fabricated with polyethylene glycol (PEG 4000) as the carrier at appropriate puerarin/PEG 4000 ratios, assessed through differential scanning calorimetry (DSC), solubility, and dissolution tests. The novel structures of 3D-printed tablets with five different values were formed by printing paths, which established a flexible way of adjusting in vitro drug release. An obvious acceleration (85% of cumulative release about 7.5 min at the soonest) was observed for the tablets with internal structural design. It was inferred that puerarin formed simple eutectic mixtures with PEG 4000 and that puerarin dispersed into the carrier based on DSC and X-Ray powder diffraction (XRD). This highlights the combined advantage of PEG as a soluble polymer with TE 3D printing and provides a suitable system for rapid puerarin release.

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5


  1. 1.

    Park S, Jun S. Statistical technology analysis for competitive sustainability of three dimensional printing. Sustainability. 2017;9(7):1142.

    Google Scholar 

  2. 2.

    Preis M, Öblom H. 3D-printed drugs for children—are we ready yet? AAPS PharmSciTech. 2017;18(2):303–8.

    PubMed  PubMed Central  Google Scholar 

  3. 3.

    Melocchi A, Parietti F, Maccagnan S, Ortenzi MA, Antenucci S, Briatico-Vangosa F, et al. Industrial development of a 3D-printed nutraceutical delivery platform in the form of a multicompartment HPC capsule. AAPS PharmSciTech. 2018;19(8):3343–54.

    CAS  PubMed  Google Scholar 

  4. 4.

    Nukala PK, Palekar S, Patki M, Patel K. Abuse deterrent immediate release egg-shaped tablet (egglets) using 3D printing technology: quality by design to optimize drug release and extraction. AAPS PharmSciTech. 2019;20(2):80.

    PubMed  Google Scholar 

  5. 5.

    Öblom H, Zhang J, Pimparade M, Speer I, Preis M, Repka M, et al. 3D-printed isoniazid tablets for the treatment and prevention of tuberculosis—personalized dosing and drug release. AAPS PharmSciTech. 2019;20(2):52.

    PubMed  PubMed Central  Google Scholar 

  6. 6.

    Korte C, Quodbach J. 3D-printed network structures as controlled-release drug delivery systems: dose adjustment, API release analysis and prediction. AAPS PharmSciTech. 2018;19(8):3333–42.

    CAS  PubMed  PubMed Central  Google Scholar 

  7. 7.

    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  Google Scholar 

  8. 8.

    Sadia M, Arafat B, Ahmed W, Forbes RE, Alhnan MA. Channelled tablets: an innovative approach to accelerating drug release from 3D printed tablets. J Control Release. 2017;269:1–32.

    Google Scholar 

  9. 9.

    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  Google Scholar 

  10. 10.

    Li Q, Guan X, Cui M, Zhu Z, Chen K, Wen H, et al. Preparation and investigation of novel gastro-floating tablets with 3D extrusion-based printing. Int J Pharm. 2018;535(1-2).

  11. 11.

    Martinez PR, Goyanes A, Basit AW, Gaisford S. Influence of geometry on the drug release profiles of stereolithographic (SLA) 3D-printed tablets. AAPS PharmSciTech. 2018;19(8):3355–61.

    CAS  PubMed  Google Scholar 

  12. 12.

    Khaled SA, Alexander MR, Irvine DJ, Wildman RD, Wallace MJ, Sharpe S, et al. Extrusion 3D printing of paracetamol tablets from a single formulation with tunable release profiles through control of tablet geometry. AAPS PharmSciTech. 2018;19(8):3403–13.

    CAS  PubMed  PubMed Central  Google Scholar 

  13. 13.

    Wen H, He B, Wang H, Chen F, Li P, Cui M, et al. Structure-based gastro-retentive and controlled-release drug delivery with novel 3D printing. AAPS PharmSciTech. 2019;20(2):68.

    PubMed  Google Scholar 

  14. 14.

    Melocchi A, Parietti F, Loreti G, Maroni A, Gazzaniga A, Zema L. 3D printing by fused deposition modeling (FDM) of a swellable/erodible capsular device for oral pulsatile release of drugs. J Drug Deliv Sci Technol. 2015;30:360–7.

    CAS  Google Scholar 

  15. 15.

    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(1):659–68.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. 16.

    Alvaro G, Buanz ABM, Hatton GB, Simon G, Basit AW. 3D printing of modified-release aminosalicylate (4-ASA and 5-ASA) tablets. Eur J Pharm Biopharm. 2015;89:157–62.

    Google Scholar 

  17. 17.

    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(11):1–9.

    Google Scholar 

  18. 18.

    Kempin W, Domsta V, Grathoff G, Brecht I, Semmling B, Tillmann S, et al. Immediate release 3D-printed tablets produced via fused deposition modeling of a thermo-sensitive drug. Pharm Res. 2018;35(6):124.

    PubMed  Google Scholar 

  19. 19.

    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.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. 20.

    Guyot M, Fawaz F, Bildet J, Bonini F, Lagueny A-M. Physicochemical characterization and dissolution of norfloxacin/cyclodextrin inclusion compounds and PEG solid dispersions. Int J Pharm. 1995;123(1):53–63.

    CAS  Google Scholar 

  21. 21.

    Betageri GV, Makarla KR. Enhancement of dissolution of glyburide by solid dispersion and lyophilization techniques. Int J Pharm. 1995;126(1–2):155–60.

    CAS  Google Scholar 

  22. 22.

    Doshi DH, Ravis WR, Betageri GV. Carbamazepine and polyethylene glycol solid dispersions: preparation, in vitro dissolution, and characterization. Drug Dev Commun. 2008;23(12):1167–76.

    Google Scholar 

  23. 23.

    Zerrouk N, Chemtob C, Arnaud P, Toscani S, Dugue J. In vitro and in vivo evaluation of carbamazepine-PEG 6000 solid dispersions. Int J Pharm. 2001;225(1):49–62.

    CAS  PubMed  Google Scholar 

  24. 24.

    Law D, Schmitt EA, Marsh KC, Everitt EA, Wang W, Fort JJ, et al. Ritonavir-PEG 8000 amorphous solid dispersions: in vitro and in vivo evaluations. J Pharm Sci. 2004;93(3):563–70.

    CAS  PubMed  Google Scholar 

  25. 25.

    Liu C, Desai KGH. Characteristics of rofecoxib-polyethylene glycol 4000 solid dispersions and tablets based on solid dispersions. Pharm Dev Technol. 2005;10(4):467–77.

    CAS  PubMed  Google Scholar 

  26. 26.

    Chia-Chi C, Wen-Hsiung C. Impact effects of puerarin on mouse embryonic development. Reprod Toxicol. 2009;28(4):530–5.

    Google Scholar 

  27. 27.

    Choi YM, Jun HJ, Dawson K, Rodriguez RL, Mi RR, Jun J, et al. Effects of the isoflavone puerarin and its glycosides on melanogenesis in B16 melanocytes. Eur Food Res Technol. 2010;231(1):75–83.

    CAS  Google Scholar 

  28. 28.

    Luo CF, Yuan M, Chen MS, Liu SM, Zhu L, Huang BY, et al. Pharmacokinetics, tissue distribution and relative bioavailability of puerarin solid lipid nanoparticles following oral administration. Int J Pharm. 2011;410(1):138–44.

    CAS  Google Scholar 

  29. 29.

    Jia S, Zhen M, Hui S, Xing D, Yi D, Du L. Different kinetics of puerarin in plasma of normal and depressed rats after oral administration of Chinese medicine TZ18. Tsinghua Sci Technol. 2007;12(4):394–9.

    Google Scholar 

  30. 30.

    Zhang Y, Wang R, Wu J, Shen Q. Characterization and evaluation of self-microemulsifying sustained-release pellet formulation of puerarin for oral delivery. Int J Pharm. 2012;427(2):337–44.

    CAS  Google Scholar 

  31. 31.

    Hongfei W, An Z, Chuanhua L, Lei W. Examination of lymphatic transport of puerarin in unconscious lymph duct-cannulated rats after administration in microemulsion drug delivery systems. Eur J Pharm Sci. 2011;42(4):348–53.

    Google Scholar 

  32. 32.

    Deshkar SS, Borde G, Kale R, Waghmare B, Thomas AB. Formulation of cilostazol spherical agglomerates by crystallo-co-agglomeration technique and optimization using design of experimentation. Int J Pharm Investig. 2017;7(4):164–73.

    CAS  PubMed  PubMed Central  Google Scholar 

  33. 33.

    Shah VP, Tsong Y, Sathe P, Liu J-P. In vitro dissolution profile comparison—statistics and analysis of the similarity factor, f2. Pharm Res. 1998;15(6):889–96.

    CAS  Google Scholar 

  34. 34.

    Karalis V, Magklara E, Shah VP, Macheras P. From drug delivery systems to drug release, dissolution, IVIVC, BCS, BDDCS, bioequivalence and biowaivers. Pharm Res. 2010;27(9):2018–29.

    CAS  Google Scholar 

  35. 35.

    Costa P, Lobo JMS. Divisability of diltiazem matrix sustained-release tablets. Pharm Dev Technol. 2001;6(3):343–51.

    CAS  PubMed  Google Scholar 

  36. 36.

    Costa P. An alternative method to the evaluation of similarity factor in dissolution testing. Int J Pharm. 2001;220(1):77–83.

    CAS  Google Scholar 

  37. 37.

    Wang Q, Yu D-G, Zhang L-L, Liu X-K, Deng Y-C, Zhao M. Electrospun hypromellose-based hydrophilic composites for rapid dissolution of poorly water-soluble drug. Carbohydr Polym. 2017;174:617–25.

    CAS  PubMed  Google Scholar 

  38. 38.

    Huang W, Hou Y, Lu X, Gong Z, Yang Y, Lu X-J, et al. The process–property–performance relationship of medicated nanoparticles prepared by modified coaxial electrospraying. Pharmaceutics. 2019;11(5):226.

    CAS  PubMed Central  Google Scholar 

  39. 39.

    Huang W, Yang Y, Zhao B, Liang G, Liu S, Liu X-L, et al. Fast dissolving of ferulic acid via electrospun ternary amorphous composites produced by a coaxial process. Pharmaceutics. 2018;10(3):115.

    CAS  PubMed Central  Google Scholar 

  40. 40.

    Li J-J, Yang Y-Y, Yu D-G, Du Q, Yang X-L. Fast dissolving drug delivery membrane based on the ultra-thin shell of electrospun core-shell nanofibers. Eur J Pharm Sci. 2018;122:195–204.

    CAS  PubMed  Google Scholar 

  41. 41.

    Liu Z-P, Zhang L-L, Yang Y-Y, Wu D, Jiang G, Yu D-G. Preparing composite nanoparticles for immediate drug release by modifying electrohydrodynamic interfaces during electrospraying. Powder Technol. 2018;327:179–87.

    CAS  Google Scholar 

  42. 42.

    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.

    CAS  Google Scholar 

  43. 43.

    Shah JC, Chen JR, Chow D. Preformulation study of etoposide: II. Increased solubility and dissolution rate by solid-solid dispersions. Int J Pharm. 1995;113(1):103–11.

    CAS  Google Scholar 

  44. 44.

    Matsuda Y, Tatsumi E. Physicochemical characterization of furosemide modifications. Int J Pharm. 1990;60(1):11–26.

    CAS  Google Scholar 

  45. 45.

    Khattab IS, Nada A, Zaghloul AA. Physicochemical characterization of gliclazide-macrogol solid dispersion and tablets based on optimized dispersion. Drug Dev Ind Pharm. 2010;36(8):893–902.

    CAS  PubMed  Google Scholar 

Download references


We are grateful for the instruments purchased from Jingxin Pharmaceutical Co., Ltd. (Zhejiang, China).


This work was supported by National Science and Technology Major Project which belongs to “The research on the key technology of new drug delivery system and industrialization of new projects” (No. 2017ZX09201-003-011).

Author information



Corresponding authors

Correspondence to Fei Yin or Xinggang Yang.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Li, P., Jia, H., Zhang, S. et al. Thermal Extrusion 3D Printing for the Fabrication of Puerarin Immediate-Release Tablets. AAPS PharmSciTech 21, 20 (2020).

Download citation


  • three-dimensional printing
  • thermal extrusion
  • low temperature
  • immediate release tablet
  • polyethylene glycol