Skip to main content
SpringerLink
Log in

The advent of a novel manufacturing technology in pharmaceutics: superiority of fused deposition modeling 3D printer

  • Review
  • Published:
Journal of Pharmaceutical Investigation Aims and scope Submit manuscript

Abstract

Background

Three-dimensional (3D) printing is a process for creating 3D objects with various geometries using digital modeling, and it is widely used in the construction and medical industries. In the field of pharmacy, 3D printers were introduced as a suitable manufacturing method in response to the increasing need for “personalization.” Since the first 3D printed drug, Spritam®, was approved by the Food and Drug Administration (FDA) in 2015, 3D printer technology has evolved through considerable research. The 3D printing methods are classified into selective laser sintering, inkjet printing, stereolithography, digital light processing, and fused deposition modeling (FDM) according to the printing method. Among them, FDM, which is a method of extruding filaments through a nozzle, is the most widely used 3D printer method in pharmaceuticals.

Area covered

This review paper covers the detail content of manufacturing drugs by FDM. Owing to its ease of use and relatively low price, many studies have focused on FDM 3D printers. In this review paper, we concretely investigate a series of FDM procedures and parameters and introduce many studies that used FDM 3D printers to control the release, to make novel dosage form, and to deliver the customized doses.

Expert opinion

FDM is completely different from traditional drug manufacturing methods, and it is expected to achieve personalization. Once mechanical problems and regulatory barriers are overcome and new developments are made, FDM 3D printers will become a unique and effective way to manufacture patient-customized drugs in the pharmaceutical industry.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Reproduced and modified with permission from Elsevier

Fig. 4

Similar content being viewed by others

References

  • Abuzar SM, Hyun SM, Kim JH, Park HJ, Kim MS, Park JS, Hwang SJ (2018) Enhancing the solubility and bioavailability of poorly water-soluble drugs using supercritical antisolvent (SAS) process. Int J Pharm 538:1–13

    CAS  PubMed  Google Scholar 

  • Alhijjaj M, Belton P, Qi S (2016) An investigation into the use of polymer blends to improve the printability of and regulate drug release from pharmaceutical solid dispersions prepared via fused deposition modeling (FDM) 3D printing. Eur J Pharm Biopharm 108:111–125

    CAS  PubMed  Google Scholar 

  • Al-Metwali B, Mulla H (2017) Personalised dosing of medicines for children. J Pharm Pharmacol 69:514–524

    CAS  PubMed  Google Scholar 

  • Anitha R, Arunachalam S, Radhakrishnan P (2001) Critical parameters influencing the quality of prototypes in fused deposition modelling. J Mater Process Technol 118:385–388

    Google Scholar 

  • Arafat B, Qinna N, Cieszynska M, Forbes RT, Alhnan MA (2018a) Tailored on demand anti-coagulant dosing: an in vitro and in vivo evaluation of 3D printed purpose-designed oral dosage forms. Eur J Pharm Biopharm 128:282–289

    CAS  PubMed  Google Scholar 

  • Arafat B, Wojsz M, Isreb A, Forbes RT, Isreb M, Ahmed W, Arafat T, Alhnan MA (2018b) Tablet fragmentation without a disintegrant: a novel design approach for accelerating disintegration and drug release from 3D printed cellulosic tablets. Eur J Pharm Sci 118:191–199

    CAS  PubMed  Google Scholar 

  • Cann O (2018) These are the top 10 emerging technologies of 2018 Head of Media Content, World Economic Forum https://www.weforum.org/agenda/2018/09/top-10-emerging-technologies-of-2018/. Accessed 14 Sept 2018

  • Carneiro OS, Silva AF, Gomes R (2015) Fused deposition modeling with polypropylene. Mater Des 83:768–776

    CAS  Google Scholar 

  • Chai X, Chai H, Wang X, Yang J, Li J, Zhao Y, Cai W, Tao T, Xiang X (2017) Fused deposition modeling (FDM) 3D printed tablets for intragastric floating delivery of domperidone. Sci Rep 7:2829

    PubMed  PubMed Central  Google Scholar 

  • Cohen JS (1999) Ways to minimize adverse drug reactions. Postgrad Med 106:163–172

    CAS  PubMed  Google Scholar 

  • Crowley MM, Zhang F, Repka MA, Thumma S, Upadhye SB, Battu SK, Mcginity JW, Martin C (2007) Pharmaceutical applications of hot-melt extrusion: part I. Drug Dev Ind Pharm 33:909–926

    CAS  PubMed  Google Scholar 

  • Economidou SN, Lamprou DA, Douroumis D (2018) 3D printing applications for transdermal drug delivery. Int J Pharm 544:415–424

    CAS  PubMed  Google Scholar 

  • Fule R, Meer T, Amin P, Dhamecha D, Ghadlinge S (2013) Preparation and characterisation of lornoxicam solid dispersion systems using hot melt extrusion technique. J Pharm Investig 44:41

    Google Scholar 

  • Genina N, Hollander J, Jukarainen H, Makila E, Salonen J, Sandler N (2016) Ethylene vinyl acetate (EVA) as a new drug carrier for 3D printed medical drug delivery devices. Eur J Pharm Sci 90:53–63

    CAS  PubMed  Google Scholar 

  • Genina N, Boetker JP, Colombo S, Harmankaya N, Rantanen J, Bohr A (2017) Anti-tuberculosis drug combination for controlled oral delivery using 3D printed compartmental dosage forms: from drug product design to in vivo testing. J Control Release 268:40–48

    CAS  PubMed  Google Scholar 

  • Gioumouxouzis CI, Katsamenis OL, Bouropoulos N, Fatouros DG (2017) 3D printed oral solid dosage forms containing hydrochlorothiazide for controlled drug delivery. J Drug Deliv Sci Tec 40:164–171

    CAS  Google Scholar 

  • Gioumouxouzis CI, Baklavaridis A, Katsamenis OL, Markopoulou CK, Bouropoulos N, Tzetzis D, Fatouros DG (2018a) A 3D printed bilayer oral solid dosage form combining metformin for prolonged and glimepiride for immediate drug delivery. Eur J Pharm Sci 120:40–52

    CAS  PubMed  Google Scholar 

  • Gioumouxouzis CI, Chatzitaki AT, Karavasili C, Katsamenis OL, Tzetzis D, Mystiridou E, Bouropoulos N, Fatouros DG (2018b) Controlled release of 5-fluorouracil FROm alginate beads encapsulated in 3D printed pH-responsive solid dosage forms. AAPS PharmSciTech 19:3362–3375

    CAS  PubMed  Google Scholar 

  • Gonzalez-Gutierrez J (2017) Filler content & properties of highly filled filaments for fused filament fabrication of magents. Proc ANTEC 2017:1–4

    Google Scholar 

  • Goole J, Amighi K (2016) 3D printing in pharmaceutics: a new tool for designing customized drug delivery systems. Int J Pharm 499:376–394

    PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Goyanes A, Buanz AB, Hatton GB, Gaisford S, Basit AW (2015a) 3D printing of modified-release aminosalicylate (4-ASA and 5-ASA) tablets. Eur J Pharm Biopharm 89:157–162

    CAS  PubMed  Google Scholar 

  • Goyanes A, Robles Martinez P, Buanz A, Basit AW, Gaisford S (2015b) Effect of geometry on drug release from 3D printed tablets. Int J Pharm 494:657–663

    CAS  PubMed  Google Scholar 

  • Goyanes A, Fina F, Martorana A, Sedough D, Gaisford S, Basit AW (2017a) Development of modified release 3D printed tablets (printlets) with pharmaceutical excipients using additive manufacturing. Int J Pharm 527:21–30

    CAS  PubMed  Google Scholar 

  • Goyanes A, Scarpa M, Kamlow M, Gaisford S, Basit AW, Orlu M (2017b) Patient acceptability of 3D printed medicines. Int J Pharm 530:71–78

    CAS  PubMed  Google Scholar 

  • Hull CW (1986) Apparatus for production of three-dimensional objects by stereolithography. US4575330A

  • Hwang I, Kang C-Y, Park J-B (2017) Advances in hot-melt extrusion technology toward pharmaceutical objectives. J Pharm Investig 47:123–132

    CAS  Google Scholar 

  • Ionita CN, Mokin M, Varble N, Bednarek DR, Xiang J, Snyder KV, Siddiqui AH, Levy EI, Meng H, Rudin S (2014) Challenges and limitations of patient-specific vascular phantom fabrication using 3D Polyjet printing. Proc SPIE Int Soc Opt Eng 9038:90380M

    PubMed  Google Scholar 

  • Jakus AE, Taylor SL, Geisendorfer NR, Dunand DC, Shah RN (2015) Metallic architectures from 3D-printed powder-based liquid inks. Adv Funct Mater 25:6985–6995

    CAS  Google Scholar 

  • Jamroz W, Kurek M, Lyszczarz E, Szafraniec J, Knapik-Kowalczuk J, Syrek K, Paluch M, Jachowicz R (2017) 3D printed orodispersible films with Aripiprazole. Int J Pharm 533:413–420

    CAS  PubMed  Google Scholar 

  • Kadry H, Al-Hilal TA, Keshavarz A, Alam F, Xu C, Joy A, Ahsan F (2018) Multi-purposable filaments of HPMC for 3D printing of medications with tailored drug release and timed-absorption. Int J Pharm 544:285–296

    CAS  PubMed  Google Scholar 

  • Kalivoda A, Fischbach M, Kleinebudde P (2012) Application of mixtures of polymeric carriers for dissolution enhancement of fenofibrate using hot-melt extrusion. Int J Pharm 429:58–68

    CAS  PubMed  Google Scholar 

  • Karlsson MO, Lutsar I, Milligan PA (2009) Population pharmacokinetic analysis of voriconazole plasma concentration data from pediatric studies. Antimicrob Agents Chemother 53:935–944

    CAS  PubMed  Google Scholar 

  • Kempin W, Domsta V, Brecht I, Semmling B, Tillmann S, Weitschies W, Seidlitz A (2018a) Development of a dual extrusion printing technique for an acid- and thermo-labile drug. Eur J Pharm Sci 123:191–198

    CAS  PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  • Korte C, Quodbach J (2018) 3D-printed network structures as controlled-release drug delivery systems: dose adjustment, API release analysis and prediction. AAPS PharmSciTech 19:3333–3342

    CAS  PubMed  Google Scholar 

  • Kruth JP, Wang X, Laoui T, Froyen L (2003) Lasers and materials in selective laser sintering. Assembly Autom 23:357–371

    Google Scholar 

  • Lepowsky STE (2018) 3D printing for drug manufacturing: a perspective on the future of pharmaceuticals. Int J Bioprint 4:119

    Google Scholar 

  • Li Q, Wen H, Jia D, Guan X, Pan H, Yang Y, Yu S, Zhu Z, Xiang R, Pan W (2017) Preparation and investigation of controlled-release glipizide novel oral device with three-dimensional printing. Int J Pharm 525:5–11

    CAS  PubMed  Google Scholar 

  • Luzuriaga MA, Berry DR, Reagan JC, Smaldone RA, Gassensmith JJ (2018) Biodegradable 3D printed polymer microneedles for transdermal drug delivery. Lab Chip 18:1223–1230

    CAS  PubMed  Google Scholar 

  • Maroni A, Melocchi A, Parietti F, Foppoli A, Zema L, Gazzaniga A (2017) 3D printed multi-compartment capsular devices for two-pulse oral drug delivery. J Control Release 268:10–18

    CAS  PubMed  Google Scholar 

  • Mcdougall DA, Martin J, Playford EG, Green B (2016) Determination of a suitable voriconazole pharmacokinetic model for personalised dosing. J Pharmacokinet Pharmacodyn 43:165–177

    CAS  PubMed  Google Scholar 

  • Melchels FP, Feijen J, Grijpma DW (2010) A review on stereolithography and its applications in biomedical engineering. Biomaterials 31:6121–6130

    CAS  PubMed  Google Scholar 

  • Melocchi A, Parietti F, Loreti G, Maroni A, Gazzaniga A, Zema L (2015) 3D printing by fused deposition modeling (FDM) of a swellable/erodible capsular device for oral pulsatile release of drugs. J Drug Deliv Sci Technol 30:360–367

    CAS  Google Scholar 

  • Melocchi A, Parietti F, Maroni A, Foppoli A, Gazzaniga A, Zema L (2016) Hot-melt extruded filaments based on pharmaceutical grade polymers for 3D printing by fused deposition modeling. Int J Pharm 509:255–263

    CAS  PubMed  Google Scholar 

  • Mohanty S, Larsen LB, Trifol J, Szabo P, Burri HV, Canali C, Dufva M, Emneus J, Wolff A (2015) Fabrication of scalable and structured tissue engineering scaffolds using water dissolvable sacrificial 3D printed moulds. Mater Sci Eng C Mater Biol Appl 55:569–578

    CAS  PubMed  Google Scholar 

  • Mohiti-Asli M, Pourdeyhimi B, Loboa EG (2014) Skin tissue engineering for the infected wound site: biodegradable PLA nanofibers and a novel approach for silver ion release evaluated in a 3D coculture system of keratinocytes and Staphylococcus aureus. Tissue Eng Part C Methods 20:790–797

    CAS  PubMed  PubMed Central  Google Scholar 

  • Okwuosa TC, Stefaniak D, Arafat B, Isreb A, Wan KW, Alhnan MA (2016) A lower temperature FDM 3D printing for the manufacture of patient-specific immediate release tablets. Pharm Res 33:2704–2712

    CAS  PubMed  Google Scholar 

  • Okwuosa TC, Pereira BC, Arafat B, Cieszynska M, Isreb A, Alhnan MA (2017) Fabricating a shell-core delayed release tablet using dual FDM 3D printing for patient-centred therapy. Pharm Res 34:427–437

    CAS  PubMed  Google Scholar 

  • Okwuosa TC, Soares C, Gollwitzer V, Habashy R, Timmins P, Alhnan MA (2018) On demand manufacturing of patient-specific liquid capsules via co-ordinated 3D printing and liquid dispensing. Eur J Pharm Sci 118:134–143

    CAS  PubMed  Google Scholar 

  • Park BJ, Choi HJ, Moon SJ, Kim SJ, Bajracharya R, Min JY, Han H-K (2018) Pharmaceutical applications of 3D printing technology: current understanding and future perspectives. J Pharm Investig. https://doi.org/10.1007/s40005-40018-00414-y

    Article  Google Scholar 

  • Pate N, Naruka PS, Chauhan DCS, Modi J (2013) Formulation development and evaluation of immediate release tablet of topiramateanti epileptic drug. J Pharm Sci Bio-sci Res 3:58–65

    Google Scholar 

  • Patel DK, Sakhaei AH, Layani M, Zhang B, Ge Q, Magdassi S (2017) Highly stretchable and UV curable elastomers for digital light processing based 3D printing. Adv Mater. https://doi.org/10.1002/adma.201606000

    Article  PubMed  Google Scholar 

  • Pere CPP, Economidou SN, Lall G, Ziraud C, Boateng JS, Alexander BD, Lamprou DA, Douroumis D (2018) 3D printed microneedles for insulin skin delivery. Int J Pharm 544:425–432

    CAS  PubMed  Google Scholar 

  • Pietrzak K, Isreb A, Alhnan MA (2015) A flexible-dose dispenser for immediate and extended release 3D printed tablets. Eur J Pharm Biopharm 96:380–387

    CAS  PubMed  Google Scholar 

  • Raymond C, Rowe PJS, Quinn ME (2009) Handbook of pharmaceutical excipients. Pharmaceutical Press, London

    Google Scholar 

  • Repka MA, Majumdar S, Kumar Battu S, Srirangam R, Upadhye SB (2008) Applications of hot-melt extrusion for drug delivery. Expert Opin Drug Deliv 5:1357–1376

    CAS  PubMed  Google Scholar 

  • Sadia M, Sosnicka A, Arafat B, Isreb A, Ahmed W, Kelarakis A, Alhnan MA (2016) Adaptation of pharmaceutical excipients to FDM 3D printing for the fabrication of patient-tailored immediate release tablets. Int J Pharm 513:659–668

    CAS  PubMed  Google Scholar 

  • Sadia M, Arafat B, Ahmed W, Forbes RT, Alhnan MA (2018) Channelled tablets: an innovative approach to accelerating drug release from 3D printed tablets. J Control Release 269:355–363

    CAS  PubMed  Google Scholar 

  • Scoutaris N, Ross SA, Douroumis D (2018) 3D printed “Starmix” drug loaded dosage forms for paediatric applications. Pharm Res 35:34

    PubMed  Google Scholar 

  • Sehgal S (2015) FDA Approval letter. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207958Orig1s000ChemR.pdf. Accesed 27 Feb 2015

  • Serra T, Planell JA, Navarro M (2013) High-resolution PLA-based composite scaffolds via 3-D printing technology. Acta Biomater 9:5521–5530

    CAS  PubMed  Google Scholar 

  • Shishoo CJ, Shah SA, Rathod IS, Savale SS, Vora MJ (2001) Impaired bioavailability of rifampicin in presence of isoniazid from fixed dose combination (FDC) formulation. Int J Pharm 228:53–67

    CAS  PubMed  Google Scholar 

  • Skowyra J, Pietrzak K, Alhnan MA (2015) Fabrication of extended-release patient-tailored prednisolone tablets via fused deposition modelling (FDM) 3D printing. Eur J Pharm Sci 68:11–17

    CAS  PubMed  Google Scholar 

  • Smith DM, Kapoor Y, Klinzing GR, Procopio AT (2018) Pharmaceutical 3D printing: design and qualification of a single step print and fill capsule. Int J Pharm 544:21–30

    CAS  PubMed  Google Scholar 

  • Solanki NG, Tahsin M, Shah AV, Serajuddin ATM (2018) Formulation of 3D printed tablet for rapid drug release by fused deposition modeling: screening polymers for drug release, drug-polymer miscibility and printability. J Pharm Sci 107:390–401

    CAS  PubMed  Google Scholar 

  • Spoerk M, Gonzalez-Gutierrez J, Sapkota J, Schuschnigg S, Holzer C (2017) Effect of the printing bed temperature on the adhesion of parts produced by fused filament fabrication. Plast, Rubber Compos 47:17–24

    Google Scholar 

  • Strickley RG, Iwata Q, Wu S, Dahl TC (2008) Pediatric drugs—a review of commercially available oral formulations. J Pharm Sci 97:1731–1774

    CAS  PubMed  Google Scholar 

  • Tagami T, Nagata N, Hayashi N, Ogawa E, Fukushige K, Sakai N, Ozeki T (2018) Defined drug release from 3D-printed composite tablets consisting of drug-loaded polyvinylalcohol and a water-soluble or water-insoluble polymer filler. Int J Pharm 543:361–367

    CAS  PubMed  Google Scholar 

  • Tran N-H, Nguyen V-N, Ngo A-V, Nguyen V-C (2017) Study on the effect of fused deposition modeling (FDM) process parameters on the printed part quality. Int J Eng Res Appl 7:71–77

    Google Scholar 

  • Tume JN, Scarpacel PJ, Lowenthal DT (1992) Geriatric phamacology: basic and clinical considerations. Annu Rev Pharmacol Toxicol 32:271–302

    Google Scholar 

  • Ventola MCL (2014) Medical applications for 3D printing: current and projected uses. Pharmacy Therapeutics 39:704–711

    PubMed  Google Scholar 

  • Verstraete G, Samaro A, Grymonpre W, Vanhoorne V, Van Snick B, Boone MN, Hellemans T, Van Hoorebeke L, Remon JP, Vervaet C (2018) 3D printing of high drug loaded dosage forms using thermoplastic polyurethanes. Int J Pharm 536:318–325

    CAS  PubMed  Google Scholar 

  • Wang CC, Lin TW, Hu SS (2007) Optimizing the rapid prototyping process by integrating the Taguchi method with the Gray relational analysis. Rapid Prototyp J 13:304–315

    Google Scholar 

  • Wittbrodt B, Laureto J, Tymrak B, Pearce JM (2015) Distributed manufacturing with 3-D printing: a case study of recreational vehicle solar photovoltaic mounting systems. J Frugal Innov 1:1

    Google Scholar 

  • Yanni SB, Annaert PP, Augustijns P, Ibrahim JG, Benjamin DK Jr, Thakker DR (2010) In vitro hepatic metabolism explains higher clearance of voriconazole in children versus adults: role of CYP2C19 and flavin-containing monooxygenase 3. Drug Metab Dispos 38:25–31

    CAS  PubMed  PubMed Central  Google Scholar 

  • Yi HG, Choi YJ, Kang KS, Hong JM, Pati RG, Park MN, Shim IK, Lee CM, Kim SC, Cho DW (2016) A 3D-printed local drug delivery patch for pancreatic cancer growth suppression. J Control Release 238:231–241

    CAS  PubMed  Google Scholar 

  • Zhang J, Feng X, Patil H, Tiwari RV, Repka MA (2017) Coupling 3D printing with hot-melt extrusion to produce controlled-release tablets. Int J Pharm 519:186–197

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors would like to acknowledge Yonsei Institute of Pharmaceutical Sciences, Yonsei University for their writing assistance.

Funding

This review was supported by the Basic Science Research Program (2017R1D1A1B03031213) and Basic Research Infrastructure Support Program (University-Centered Labs-2018R1A6A1A03023718) through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning, Republic of Korea.

Author information

Authors and Affiliations

  1. College of Pharmacy, Yonsei University, 85 Songdogwahak-ro, Yeonsu-gu, Incheon, 21983, Republic of Korea

    Yechan Joo, Intaek Shin, Gunjoo Ham, Sharif Md Abuzar, Sang-Min Hyun & Sung-Joo Hwang

  2. Yonsei Institute of Pharmaceutical Sciences, Yonsei University, 85 Songdogwahak-ro, Yeonsu-gu, Incheon, 21983, Republic of Korea

    Yechan Joo, Intaek Shin, Gunjoo Ham, Sharif Md Abuzar, Sang-Min Hyun & Sung-Joo Hwang

Authors
  1. Yechan Joo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Intaek Shin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gunjoo Ham
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sharif Md Abuzar
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sang-Min Hyun
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Sung-Joo Hwang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sung-Joo Hwang.

Ethics declarations

Conflict of interest

All authors declare that they have no conflict of interest.

Statement of human and animal rights

The article does not contain any studies with human and animal subjects performed by any of the authors.

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

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Joo, Y., Shin, I., Ham, G. et al. The advent of a novel manufacturing technology in pharmaceutics: superiority of fused deposition modeling 3D printer. J. Pharm. Investig. 50, 131–145 (2020). https://doi.org/10.1007/s40005-019-00451-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40005-019-00451-1

Keywords

Search

Navigation