3DP printing of oral solid formulations: a systematic review

Journal article

Brambilla, C., Okafor-Muo, O., Hassanin, H. and ElShaer, A. 2021. 3DP printing of oral solid formulations: a systematic review. Pharmaceutics. 13 (3), p. 358. https://doi.org/10.3390/pharmaceutics13030358
AuthorsBrambilla, C., Okafor-Muo, O., Hassanin, H. and ElShaer, A.

Three-dimensional (3D) printing is a recent technology, which gives the possibility to manufacture personalised dosage forms and it has a broad range of applications. One of the most developed, it is the manufacture of oral solid dosage and the four 3DP techniques which have been more used for their manufacture are FDM, inkjet 3DP, SLA and SLS. This systematic review is carried out to statistically analyze the current 3DP techniques employed in manufacturing oral solid formulations and assess the recent trends of this new technology. The work has been organised into four steps, (1) screening of the articles, definition of the inclusion and exclusion criteria and classi-fication of the articles in the two main groups (included/excluded); (2) quantification and charac-terisation of the included articles; (3) evaluation of the validity of data and data extraction process; (4) data analysis, discussion, and conclusion to define which technique offers the best properties to be applied in the manufacture of oral solid formulations. It has been observed that with SLS 3DP technique, all the characterisation tests required by the BP (drug content, drug dissolution profile, hardness, friability, disintegration time and uniformity of weight) have been performed in the majority of articles, except for the friability test. However, it is not possible to define which of the four 3DP techniques is the most suitable for the manufacture of oral solid formulations, because the selection is affected by different parameters, such as the type of formulation, the physi-cal-mechanical properties to achieve. Moreover, each technique has its specific advantages and disadvantages, such as for FDM the biggest challenge is the degradation of the drug, due to high printing temperature process or for SLA is the toxicity of the carcinogenic risk of the photopoly-merising material.

Keywords3D printing; Oral solid dosage forms; Tablets; Systematic review; Medication; Drugs
Journal citation13 (3), p. 358
Digital Object Identifier (DOI)https://doi.org/10.3390/pharmaceutics13030358
Official URLhttps://doi.org/10.3390/pharmaceutics13030358
Publication dates
Print09 Mar 2021
Publication process dates
Accepted01 Mar 2021
Deposited12 Mar 2021
Accepted author manuscript
File Access Level
Output statusPublished

1. Allahham, N.; Fina, F.; Marcuta, C.; Kraschew, L.; Mohr, W.; Gaisford, S.; Basit, A.W.; Goyanes, A. Selective laser sintering 3D printing of orally disintegrating printlets containing ondansetron. Pharmaceutics 2020, 12,110, doi.org/10.3390/pharmaceutics12020110
2. Alomari, M.; Vuddanda, P.R.; Trenfield, S.J.; Dodoo, C.C.; Velaga, S.; Basit, A.W.; Gaisford, S. Printing T.sub.3 and T.sub.4 oral drug combinations as a novel strategy for hypothyroidism. Int. J. Pharm. 2018, 549363, doi:10.1016/j.ijpharm.2018.07.062.
3. Arafat, B.; Qinna N.; Cieszynska, M; , Forbes, R. Tailored on-demand anti-coagulant dosing: An in vitro and in vivo evaluation of 3D printed purpose-designed oral dosage forms. Eur. J. Pharm. Bio-Pharm. 2018, 128, 282–289.
4. Trenfield, S.J.; Goyanes, A.; Telford, R.; Wilsdon, D.; Rowland, M.; Gaisford, S.; Basit, A.W. 3D printed drug products: Non-destructive dose verification using a rapid point-and-shoot approach. Int. J. Pharm. 2018, 549, 283–292, doi:10.1016/j.ijpharm.2018.08.002.
5. Wang, J.; Goyanes, A.; Gaisford, S.; Basit, A.W. Stereolithographic (SLA) 3D printing of oral modified-release dosage forms. Int. J. Pharm. 2016, 503, 207–212, doi:10.1016/j.ijpharm.2016.03.016.
6. Mota, C.; Puppi, D.; Chiellini, F.; Chiellini, E. Additive manufacturing techniques to produce tissue engineering constructs. J. Tissue Eng. Regen. Med. 2015, 9, 174–190, doi:10.1002/term.1635.
7. Hassanin, H.; Alkendi, Y.; Elsayed, M.; Essa, K.; Zweiri, Y. Controlling the properties of additively manufactured cellular structures using machine learning approaches. Adv. Eng. Mater. 2020, 22, 1901338, doi.org/10.1002/adem.201901338.
8. Klippstein. H.; Hassanin, H.; Diaz De Cerio Sanchez, A.; Zweiri, Y.; Seneviratne, L. Additive manufacturing of porous structures for unmanned aerial vehicles applications. Adv. Eng. Mater. 2018, 20, 1800290, doi.org/10.1002/adem.201800290.
9. Awad, A.; Fina, F.; Trenfield, S.; Patel, P.; Goyanes, A.; Gaisford, S.; Basit, A.W. 3D printed pellets (mini-printlets): A novel, multi-drug, controlled release platform technology. Pharmaceutics 2019, 11, 148, doi:10.3390/pharmaceutics11040148.
10. Galatas, A.; Hassanin, H.; Zweiri, Y.; Seneviratne, L. Additive manufactured sandwich composite/ABS parts for unmanned aerial vehicle applications. Polymers 2018, 10, 1262, doi.:10.3390/polym10111262.
11. Fina, F.; Goyanes, A.; Gaisford, S.; Basit, A.W. Selective laser sintering (SLS) 3D printing of medicines. Int. J. Pharm 2017, 529, 285–293, doi:10.1016/j.ijpharm.2017.06.082.
12. Seyfoddin, Ali.; Dezfooli Seyedehsar Masoomi, Greene Carol Ann. Engineering drug delivery systems: Duxford, CB22 4QH, United Kingdom; 2020.
13. Xu X.; Robles-Martinez, P.; Madla, C.M.; Joubert, F.; Goyanes, A.; Basit, A.; Gaisford S. Stereolithography (SLA) 3D printing of an antihypertensive polyprintlet: Case study of an unexpected photopolymer-drug reaction. Addit. Manuf. 2020, 33, 101071.
14. Fina, F.; Goyanes, A.; Madla, C.M.; Awad, A.; Trenfield, S.J.; Kuek, J.M.; Patel, P.; Gaisford, S.; Basit, A.W. 3D printing of drug-loaded gyroid lattices using selective laser sintering. Int. J. Pharm. 2018, 547, 44–52, doi:10.1016/j.ijpharm.2018.05.044.
15. Mohammed, A.; Elshaer, A.; Sareh, P.; Elsayed, M.; Hassanin, H. Additive manufacturing technologies for drug delivery applications. Int. J. Pharm. 2020, 580,119245, doi.org/10.1016/j.ijpharm.2020.119245.
16. Okafor-Muo, O.; Hassanin, H.; Kayyali, R.; ElShaer, A. 3D Printing of solid oral dosage forms: numerous challenges with unique opportunities. J. Pharm. Sci. 2020, 109, 3535–3550, doi.:10.1016/j.xphs.2020.08.029.
17. Healy, A.V.; Fuenmayor, E.; Doran, P.; Geever, L.M.; Higginbotham, C.L.; Lyons, J.G. Additive manufacturing of personalised pharmaceutical dosage forms via stereolithography. Pharmaceutics 2019, 11, 645, doi:10.3390/pharmaceutics11120645.
18. Infanger, S.; Haemmerli, A.; Iliev, S.; Baier, A.; Stoyanov, E.; Quodbach, J. Powder bed 3D-printing of highly loaded drug delivery devices with hydroxypropyl cellulose as solid binder. Int. J. Pharm. 2019, 555, 198–206, doi:10.1016/j.ijpharm.2018.11.048.
19. Cader, H.K.; Rance, G.A.; Alexander, M.R.; Gonçalves, A.D.; Roberts, C.J.; Tuck, C.J.; Wildman, R.D. Water-based 3D inkjet printing of an oral pharmaceutical dosage form. Int. J. Pharm. 2019, 564, 359–368, doi:10.1016/j.ijpharm.2019.04.026.
20. Clark, E.A.; Alexander, M.R.; Irvine, D.J.; Roberts, C.J.; Wallace, M.J.; Sharpe, S. 3D printing of tablets using inkjet with UV photoinitiation. Int. J. Pharm. 2017, 529, 523–530, doi:10.1016/j.ijpharm.2017.06.085.
21. Clark, E.A.; Alexander, M.R.; Irvine, D.J.; Roberts, C.J.; Wallace, M.J.; Yoo, J.; Wildman, R.D. Making tablets for de-livery of poorly soluble drugs using photoinitiated 3D inkjet printing. Int. J. Pharm. 2020, 578, 118805, doi:10.1016/j.ijpharm.2019.118805.
22. Jamróz, W.; Kurek, M.; Szafraniec, J.; Czech, A.; Gawlak, K.; Jachowicz R. Speed it up, slow it down-bicalutamide release from 3D printed tablets. Eur. J. Pharm. Sci. 2018, 143, 105169, doi:10.13140/rg.2.2.29139.02082.
23. Hassanin, H.; Jiang, K. Functionally graded microceramic components. Microelectron. Eng. 2010, 87, 1610–1613, doi.org/10.1016/j.mee.2009.10.044.
24. Hassanin, H.; Jiang, K. Alumina composite suspension preparation for softlithography microfabrication. Microelectron. Eng. 2009, 86, 929–932, doi.org/10.1016/j.mee.2008.12.067.
25. Hassanin, H.; Jiang, K. Fabrication of Al2O3/SiC composite microcomponents using nonaqueous suspension. Adv. Eng. Mater. 2009, 11, 101–105, doi.org/10.1002/adem.200800158.
26. Hassanin, H.; Jiang, K. Optimized process for the fabrication of zirconia micro parts. Microelectron. Eng. 2009, 11, 101–105. doi.org/10.1002/adem.200800158.
27. Schmidleithner, C.; Deepak, M.; Kalaskar, D.M. Stereolithography. 2nd ed; Oxford University Press: Oxford, UK, 2018.
28. Madzarevic, M.; Vulovic, S.; Djuris, J.; Filipovic, N.; Ibric, S.; Optimisation and prediction of ibuprofen release from 3D DLP printlets using artificial neural networks. Pharmaceutics 2019, 11, 544, doi:10.3390/pharmaceutics11100544.
29. ElShaer, A.; Hanson, P.; Worthington, T.; Lambert, P.; Mohammed, A. Preparation and characterization of amino acids-based trimethoprim salts. Pharmaceutics 2012, 4, 179–196, doi.org/10.3390/pharmaceutics4010179.
30. Kadry, H.; Wadnap, S.; Xu, C.; Ahsan, F. Digital light processing (DLP) 3D-printing technology and photoreactive polymers in fabrication of modified-release tablets. Eur. J. Pharm. Sci. 2019, 135, 60–67, doi:10.1016/j.ejps.2019.05.008.
31. Fina, F.; Madla, C.M.; Goyanes, A.; Zhang, J.; Gaisford, S.; Basit, A.W. Fabricating 3D printed orally dis-integrating printlets using selective laser sintering. Int. J. Pharm. 2018, 541, 101–107, doi:10.1016/j.ijpharm.2018.02.015.
32. Liberati, A.; Altman, D.G.; Tetzlaff, J.; Mulrow, C.; Gøtzsche, P.C.; Ioannidis, J.P.A.; et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: Explanation and elaboration. J. Clinical Epidemiol. 2009, 6, e1000100.
33. Kingston University, Pharmaceutical Technology program specification. Kingston, UK.
34. Yu, D.; Shen, X.; Branford-White, C.; Zhu.; White, K.; Yang, X.L. Novel oral fast-disintegrating drug delivery devices with predefined inner structure fabricated by three-dimensional printing. J. Pharm. Pharmacol. 2009, 61, 323–329, doi:10.1211/jpp.61.03.0006.
35. Sen, K.; Manchanda, A.; Mehta, T.; Ma, A.W.K.; Chaudhuri, B. Formulation design for inkjet-based 3D printed tablets. In-ternational. J. Pharm. 2020, 584, 119430, doi:10.1016/j.ijpharm.2020.119430.
36. Lee, B.K.; Yun, Y.H.; Choi, J.S.; Choi, Y.C.; Kim, J.D.; Cho, Y.W. Fabrication of drug-loaded polymer micro-particles with arbitrary geometries using a piezoelectric inkjet printing system. Int. J. Pharm. 2012, 427, 305¬310, doi:10.1016/j.ijpharm.2012.02.011.
37. Wilts, E.M.; Ma, D.; Bai, Y.; Williams, C.B.; Long, T.E. Comparison of linear and 4 Arm star poly (vinyl pyrrolidone) for aqueous binder jetting additive manufacturing of personalised dosage tablets. ACS Appl. Mater. Interfaces 2019, 11, 23938–23947, doi:10.1021/acsami.9b08116.
38. Genina, N.; Boetker, J.P.; Colombo, S.; Harmankaya, N.; Rantanen, J.; Bohr, A. Anti-tuberculosis drug combination for con-trolled oral delivery using 3D printed compartmental dosage forms: From drug product design to in vivo testing. J. Controll. Release 2017, 268, 40–48, doi:10.1016/j.jconrel.2017.10.003.
39. Goyanes, A.; Buanz, A.B.M.; Hatton, G.B.; Gaisford, S.; Basit, A.W. 3D printing of modified-release aminosalicylate (4-ASA and 5-ASA) tablets. Eur. J. Pharm. Biopharm.2015, 89, 157–162, doi:10.1016/j.ejpb.2014.12.003.
40. Skowyra, J.; Pietrzak, K.; Alhnan, M.A. Fabrication of extended-release patient-tailored prednisolone tablets via fused deposi-tion modelling (FDM) 3D printing. Eur. J. Pharm. Sci. 2015, 68, 11–17, doi:10.1016/j.ejps.2014.11.009.
41. Goyanes, A.; Buanz, A.B.M.; Basit, A.W.; Gaisford, S. Fused-filament 3D printing (3DP) for the fabrication of tablets. Int. J. Pharm. 2014, 476, 88–92, doi:10.1016/j.ijpharm.2014.09.044.
42. Shin, S.; Kim, T.H.; Jeong, S.W.; Chung, S.E.; Lee, D.Y.; Kim, D.; Shin, B.S. Development of a gastroretentive de-livery system for acyclovir by 3D printing technology and it is in vivo pharmacokinetic evaluation in beagle dogs. PLoS One 2019, 14, e0216875, doi:10.1371/journal.pone.0216875.
43. Tagami, T.; Fukushige, K.; Ogawa, E.; Hayashi, N.; Ozeki, T. 3D printing factors important for the fabrication of polyvinyl-alcohol filament-based tablets. Bio. Pharm. Bull. 2017, 40, 357–364, doi:10.1248/bpb. b16-00878.
44. Chen, D.; Xu, X.; Li, R.; Zang, G.A.; Zhang, Y.; Wang, M.R.; Xiong, M.F.; Xu, J.R.; Wang, T.; Fu, H.; et. al. Preparation and in vitro evaluation of FDM 3D-printed ellipsoid-shaped gastric floating tablets with low infill percentages. AAPS PharmSciTech 2020, 21, 1–13, doi:10.1208/s12249-019-1521-x.
45. Khaled, S.; Alexander, M.; Irvine, D.; Wildman, R.; Wallace, M.; Sharpe, S.; Yoo, J.; Roberts, C.J. Extrusion 3D printing of paracetamol tablets from a single formulation with tunable release profiles through control of tablet geometry. AAPS PharmSciTech 2018, 19, 3403–3413, doi:10.1208/s12249-018-1107-z.
46. Khaled, S.A.; Alexander, M.R.; Wildman, R.D.; Wallace, M.J.; Sharpe, S.; Yoo, J.; Roberts, C.J. 3D extrusion printing of high drug loading immediate release paracetamol tablets. Int. J. Pharm. 2018, 538, 223–230, doi:10.1016/j.ijpharm.2018.01.024.
47. Pietrzak, K.; Isreb, A.; Alhnan, M.A. A flexible-dose dispenser for immediate and extended-release 3D printed tablets. Eur. J. Pharm. Biopharm. 2015, 96, 380–387, doi:10.1016/j.ejpb.2015.07.027.
48. Okwuosa, T.C.; Stefaniak, D.; Arafat, B.; Isreb, A.; Wan, K.; Alhnan, M.A. A lower temperature FDM 3D printing for the manufacture of patient-specific immediate-release tablets. Pharm. Res. 2016, 33, 2704–2712, doi:10.1007/s11095-016-1995-0.
49. Li, Q.; Guan, X.; Cui, M.; Zhu, Z.; Chen, K.; Wen, H.; Jia, D.; Hou, J.; Xu, W.; Yang, X.; et. al. Preparation and investigation of novel gastrro-floating tablets with 3D extrusion-based printing. Int. J. Pharm. 2018, 535, 325–332, doi:10.1016/j.ijpharm.2017.10.037.
50. Palekar, S.; Nukala, P.K.; Mishra, S.M.; Kipping, T.; Patel, K. Application of 3D printing technology and quality by design approach for the development of an age-appropriate pediatric formulation of baclofen. Int. J. Pharm. 2019, 556, 106–116, doi:10.1016/j.ijpharm.2018.11.062.
51. Goyanes, A.; Allhham, N.; Trenfield, S.J.; Stoyanov, E.; Gaisford, S.; Basit, A.W. Direct powder extrusion 3D printing: Fabri-cation of drug products using a novel single-step process. Int. J. Pharm. 2019, 567, 118471.
52. Khaled, S.A.; Burley, J.C.; Alexander, M.R.; Yang, J.; Roberts, C.J. 3D printing of tablets containing multiple drugs with defined release profiles. Int. J. Pharm. 2015, 494, 643–650, doi:10.1016/j.ijpharm.2015.07.067.
53. Kempin, W.; Domsta, V.; Grathoff, G.; Brecht, I.; Semmling, B.; Tillmann, S.; Weitschies, W.; Seidlitz, A. Immediate release 3D-printed tablets produced via fused deposition modelling of a thermo-sensitive drug. Pharm. Res. 2018, 35, 1–12, doi:10.1007/s11095-018-2405-6.
54. Kimura, S.I.; Ishikawa, T.; Iwao, Y.; Itai, S.; Kondo, H. Fabrication of zero-order sustained-release floating tablets via fused depositing modelling 3D printer. Chem. Pharm. Bull. 2019, 67, 992–999, doi:10.1248/cpb.c19-00290.
55. Jeong, H.M.; Weon, K.; Shin, B.S.; Shin, S. 3D-printed gastroretentive sustained release drug delivery system by applying design of experiment approach. Molecules 2020, 25, 2330, doi:10.3390/molecules25102330.
56. Robles-Martinez, P.; Xu, X.; Trenfield, S..; Awad, A.; Goyanes, A.; Telford, R.; Basit, A.W.; Gaisford S. 3D printing of a mul-ti-layered polypill containing six drugs using a novel stereolithographic method. Pharmaceutics 2019, 11, 274, doi:10.3390/pharmaceutics11060274.
57. Krkobabić, M.; Medarević, D.; Cvijić, S.; Grujić, B.; Ibrić, S. Hydrophilic excipients in digital light processing (DLP) printing of sustained-release tablets: Impact on internal structure and drug dissolution rate. Int. J. Pharm. 2019, 572, 118790, doi:10.1016/j.ijpharm.2019.118790.
58. Awad, A.; Yao, A.; Trenfield, S.J.; Goyanes, A.; Gaisford, S.; Basit, A.W. 3D printed tablets (printlets) with braille and moon patterns for visually impaired patients. Pharmaceutics 2020, 12, 172.

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Authors list:
Chiara R. M. Brambilla, Ogochukwu Lilian Okafor-Muo, Hany Hassanin, and Amr ElShaer

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