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Emergence of 3D Printed Dosage Forms: Opportunities and Challenges

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Abstract

The recent introduction of the first FDA approved 3D-printed drug has fuelled interest in 3D printing technology, which is set to revolutionize healthcare. Since its initial use, this rapid prototyping (RP) technology has evolved to such an extent that it is currently being used in a wide range of applications including in tissue engineering, dentistry, construction, automotive and aerospace. However, in the pharmaceutical industry this technology is still in its infancy and its potential yet to be fully explored. This paper presents various 3D printing technologies such as stereolithographic, powder based, selective laser sintering, fused deposition modelling and semi-solid extrusion 3D printing. It also provides a comprehensive review of previous attempts at using 3D printing technologies on the manufacturing dosage forms with a particular focus on oral tablets. Their advantages particularly with adaptability in the pharmaceutical field have been highlighted, which enables the preparation of dosage forms with complex designs and geometries, multiple actives and tailored release profiles. An insight into the technical challenges facing the different 3D printing technologies such as the formulation and processing parameters is provided. Light is also shed on the different regulatory challenges that need to be overcome for 3D printing to fulfil its real potential in the pharmaceutical industry.

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Abbreviations

3D:

Three-dimensional

APIs:

Active pharmaceutical ingredients

CLIP:

Continuous layer interface production

EXT:

Semi-solid extrusion

FDM:

Fused deposition modelling

FFF:

Fused Filament Fabrication

HPC:

Hydroxypropyl cellulose

HPMC:

Hydroxypropylmethyl cellulose

PB:

Powder based

PCL:

Polycaprolactone

PEG:

Polyethylene glycol

PLLA:

Poly (−L) lactic acid

PVA:

Poly vinyl alcohol

PVP:

Polyvinylpyrrolidone

SLA:

Stereolithographic

SLS:

Selective laser sintering

References

  1. Raijada D, Genina N, Fors D, Wisaeus E, Peltonen J, Rantanen J, et al. A step toward development of printable dosage forms for poorly soluble drugs. J Pharm Sci. 2013;102(10):3694–704.

    Article  CAS  PubMed  Google Scholar 

  2. Cohen JS. Ways to minimize adverse drug reactions. Individualized doses and common sense are key. Postgrad Med. 1999;106(3):163.

    Article  CAS  PubMed  Google Scholar 

  3. Marketsandmarkets. Drug delivery technology market. 15/10/2015. Available from: http://www.marketsandmarkets.com/Market-Reports/drug-delivery-technologies-market-1085.html?gclid=CIXRuMT5osQCFe6WtAodmiUAZg.

  4. GBIResearch. Oral drug delivery market report. 16/11/2015. Available from: http://www.contractpharma.com/issues/2012-06/view_features/oral-drug-delivery-market-report/.

  5. Ervasti T, Simonaho SP, Ketolainen J, Forsberg P, Fransson M, Wikstrom H, et al. Continuous manufacturing of extended release tablets via powder mixing and direct compression. Int J Pharm. 2015;495(1):290–301.

    Article  CAS  PubMed  Google Scholar 

  6. College WCM. Study Shows Inconsistent dosages of widely used eye disease drug. 10/12/2015. Available from: http://weill.cornell.edu/news/pr/2014/09/study-shows-inconsistent-dosages-of-widely-used-eye-disease-drug-szilard-kiss-donald-damico.html.

  7. Habib WA, Alanizi AS, Abdelhamid MM, Alanizi FK. Accuracy of tablet splitting: comparison study between hand splitting and tablet cutter. Saudi Pharm J. 2014;22(5):454–9.

    Article  PubMed  Google Scholar 

  8. Helmy SA. Tablet splitting: is it worthwhile? Analysis of drug content and weight uniformity for half tablets of 16 commonly used medications in the outpatient setting. J Manag Care Spec Pharm. 2015;21(1):76–86.

    Article  PubMed  Google Scholar 

  9. Hill SW, Varker AS, Karlage K, Myrdal PB. Analysis of drug content and weight uniformity for half-tablets of 6 commonly split medications. J Manag Care Pharm. 2009;15(3):253–61.

    PubMed  Google Scholar 

  10. Tahaineh LM, Gharaibeh SF. Tablet splitting and weight uniformity of half-tablets of 4 medications in pharmacy practice. J Pharm Pract. 2012;25(4):471–6.

    Article  PubMed  Google Scholar 

  11. Pouplin T, Phuong PN, Toi PV, Nguyen Pouplin J, Farrar J. Isoniazid, pyrazinamide and rifampicin content variation in split fixed-dose combination tablets. PLoS One. 2014;9(7), e102047.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. van Riet-Nales DA, Doeve ME, Nicia AE, Teerenstra S, Notenboom K, Hekster YA, et al. The accuracy, precision and sustainability of different techniques for tablet subdivision: breaking by hand and the use of tablet splitters or a kitchen knife. Int J Pharm. 2014;466(1–2):44–51.

    Article  PubMed  CAS  Google Scholar 

  13. Erramouspe J, Jarvi EJ. Effect on dissolution from halving methylphenidate extended-release tablets. Ann Pharmacother. 1997;31(10):1123–6.

    CAS  PubMed  Google Scholar 

  14. Shah VP, Yamamoto LA, Schuirman D, Elkins J, Skelly JP. Analysis of in vitro dissolution of whole vs. half controlled-release theophylline tablets. Pharm Res. 1987;4(5):416–9.

    Article  CAS  PubMed  Google Scholar 

  15. Brown D, Ford JL, Nunn AJ, Rowe PH. An assessment of dose-uniformity of samples delivered from paediatric oral droppers. J Clin Pharm Ther. 2004;29(6):521–9.

    Article  CAS  PubMed  Google Scholar 

  16. Rosemond. Medicine management for patients with trouble swallowing pills. 12/3/2015. Available from: http://www.rosemontpharma.com/health-professionals.

  17. Schiele JT, Quinzler R, Klimm HD, Pruszydlo MG, Haefeli WE. Difficulties swallowing solid oral dosage forms in a general practice population: prevalence, causes, and relationship to dosage forms. Eur J Clin Pharmacol. 2013;69(4):937–48.

    Article  PubMed  Google Scholar 

  18. Pamudji JS, Mauludin R, Nurhabibah. Influence of β-cyclodextrin on cefixime stability in liquid suspension dosage form. Procedia Chem. 2014;13:119–27.

    Article  CAS  Google Scholar 

  19. Grießmann K, Breitkreutz J, Schubert-Zsilavecz M, Abdel-Tawab M. Dosing accuracy of measuring devices provided with antibiotic oral suspensions. Paediatr Perinat Drug Ther. 2007;8(2):61–70.

    Article  Google Scholar 

  20. Yin HS, Mendelsohn AL, Wolf MS, Parker RM, Fierman A, Van Schaick L, et al. Parents’ medication administration errors: role of dosing instruments and health literacy. Arch Pediatr Adolesc Med. 2010;164(2):181–6.

    Article  PubMed  Google Scholar 

  21. McMahon SR, Rimsza ME, Bay RC. Parents can dose liquid medication accurately. Pediatrics. 1997;100(3 Pt 1):330–3.

    Article  CAS  PubMed  Google Scholar 

  22. Scoutaris N, Alexander MR, Gellert PR, Roberts CJ. Inkjet printing as a novel medicine formulation technique. J Control Release. 2011;156(2):179–85.

    Article  CAS  PubMed  Google Scholar 

  23. Meléndez PA, Kane KM, Ashvar CS, Albrecht M, Smith PA. Thermal inkjet application in the preparation of oral dosage forms: dispensing of prednisolone solutions and polymorphic characterization by solid-state spectroscopic techniques. J Pharm Sci. 2008;97(7):2619–36.

    Article  PubMed  CAS  Google Scholar 

  24. Alomari M, Mohamed FH, Basit AW, Gaisford S. Personalised dosing: printing a dose of one’s own medicine. Int J Pharm. 2014;494(2):568–77.

    Article  PubMed  CAS  Google Scholar 

  25. Buanz AB, Saunders MH, Basit AW, Gaisford S. Preparation of personalized-dose salbutamol sulphate oral films with thermal ink-jet printing. Pharm Res. 2011;28(10):2386–92.

    Article  CAS  PubMed  Google Scholar 

  26. Boehm RD, Daniels J, Stafslien S, Nasir A, Lefebvre J, Narayan RJ. Polyglycolic acid microneedles modified with inkjet-deposited antifungal coatings. Biointerphases. 2015;10(1):011004.

    Article  PubMed  CAS  Google Scholar 

  27. Lee BK, Yun YH, Choi JS, Choi YC, Kim JD, Cho YW. Fabrication of drug-loaded polymer microparticles with arbitrary geometries using a piezoelectric inkjet printing system. Int J Pharm. 2012;427(2):305–10.

    Article  CAS  PubMed  Google Scholar 

  28. Lorber B, Hsiao WK, Hutchings IM, Martin KR. Adult rat retinal ganglion cells and glia can be printed by piezoelectric inkjet printing. Biofabrication. 2014;6(1):015001.

    Article  PubMed  CAS  Google Scholar 

  29. Uddin MJ, Scoutaris N, Klepetsanis P, Chowdhry B, Prausnitz MR, Douroumis D. Inkjet printing of transdermal microneedles for the delivery of anticancer agents. Int J Pharm. 2015;494(2):593–602.

    Article  CAS  PubMed  Google Scholar 

  30. Sandler N, Määttänen A, Ihalainen P, Kronberg L, Meierjohann A, Viitala T, et al. Inkjet printing of drug substances and use of porous substrates-towards individualized dosing. J Pharm Sci. 2011;100(8):3386–95.

    Article  CAS  PubMed  Google Scholar 

  31. Chung P, Heller JA, Etemadi M, Ottoson PE, Liu JA, Rand L, et al. Rapid and low-cost prototyping of medical devices using 3D printed molds for liquid injection molding. J Vis Exp : JoVE. 2014;88, e51745.

    PubMed  Google Scholar 

  32. Dombroski CE, Balsdon ME, Froats A. The use of a low cost 3D scanning and printing tool in the manufacture of custom-made foot orthoses: a preliminary study. BMC Res Notes. 2014;7:443.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Water JJ, Bohr A, Boetker J, Aho J, Sandler N, Nielsen HM, et al. Three-dimensional printing of drug-eluting implants: preparation of an antimicrobial polylactide feedstock material. J Pharm Sci. 2015;104(3):1099–107.

    Article  CAS  PubMed  Google Scholar 

  34. Boland T, Xu T, Damon B, Cui X. Application of inkjet printing to tissue engineering. Biotechnol J. 2006;1(9):910–7.

    Article  CAS  PubMed  Google Scholar 

  35. Pati F, Shim J-H, Lee J-S, Cho D-W. 3D printing of cell-laden constructs for heterogeneous tissue regeneration. MFGLET. 2013;1(1):49–53.

    CAS  Google Scholar 

  36. Katstra WE, Palazzolo RD, Rowe CW, Giritlioglu B, Teung P, Cima MJ. Oral dosage forms fabricated by three dimensional printing™. J Control Release. 2000;66(1):1–9.

    Article  CAS  PubMed  Google Scholar 

  37. Yu D-G, Branford-White C, Yang Y-C, Zhu L-M, Welbeck EW, Yang X-L. A novel fast disintegrating tablet fabricated by three-dimensional printing. Drug Dev Ind Pharm. 2009;35(12):1530–6.

    Article  CAS  PubMed  Google Scholar 

  38. Goyanes A, Buanz AB, Hatton GB, Gaisford S, Basit AW. 3D printing of modified-release aminosalicylate (4-ASA and 5-ASA) tablets. Eur J Pharm Biopharm. 2014;89:157–62.

    Article  PubMed  CAS  Google Scholar 

  39. Chockalingam K, Jawahar N, Chandrasekhar U. Influence of layer thickness on mechanical properties in stereolithography. Rapid Prototyp J. 2006;12(2):106–13.

    Article  Google Scholar 

  40. Huang W, Zheng Q, Sun W, Xu H, Yang X. Levofloxacin implants with predefined microstructure fabricated by three-dimensional printing technique. Int J Pharm. 2007;339(1–2):33–8.

    Article  CAS  PubMed  Google Scholar 

  41. Rowe CW, Katstra WE, Palazzolo RD, Giritlioglu B, Teung P, Cima MJ. Multimechanism oral dosage forms fabricated by three dimensional printing™. J Control Release. 2000;66(1):11–7.

    Article  CAS  PubMed  Google Scholar 

  42. Yu DG, Yang XL, Huang WD, Liu J, Wang YG, Xu H. Tablets with material gradients fabricated by three-dimensional printing. J Pharm Sci. 2007;96(9):2446–56.

    Article  CAS  PubMed  Google Scholar 

  43. Yu DG, Shen XX, Branford-White C, Zhu LM, White K, Yang XL. Novel oral fast-disintegrating drug delivery devices with predefined inner structure fabricated by Three-Dimensional Printing. J Pharm Pharmacol. 2009;61(3):323–9.

    Article  CAS  PubMed  Google Scholar 

  44. Yu DG, Branford-White C, Ma ZH, Zhu LM, Li XY, Yang XL. Novel drug delivery devices for providing linear release profiles fabricated by 3DP. Int J Pharm. 2009;370(1–2):160–6.

    Article  CAS  PubMed  Google Scholar 

  45. Gbureck U, Vorndran E, Muller FA, Barralet JE. Low temperature direct 3D printed bioceramics and biocomposites as drug release matrices. J Control Release. 2007;122(2):173–80.

    Article  CAS  PubMed  Google Scholar 

  46. Wu BM, Borland SW, Giordano RA, Cima LG, Sachs EM, Cima MJ. Solid free-form fabrication of drug delivery devices. J Control Release. 1996;40(1–2):77–87.

    Article  CAS  Google Scholar 

  47. Wu W, Zheng Q, Guo X, Sun J, Liu Y. A programmed release multi-drug implant fabricated by three-dimensional printing technology for bone tuberculosis therapy. Biomed Mater (Bristol, England). 2009;4(6):065005.

    Article  CAS  Google Scholar 

  48. Wang C-c, Yoo J, Bornancini E, Roach WJ, Motwani MR. Diffusion-controlled dosage form and method of fabrication including three dimensional printing. In.: US Patent 20,040,005,360; 2004.

  49. Leong KF, Phua KKS, Chua CK, Du ZH, Teo KOM. Fabrication of porous polymeric matrix drug delivery devices using the selective laser sintering technique. Proc Inst Mech Eng H. 2001;215(H2):191–201.

    Article  CAS  PubMed  Google Scholar 

  50. Low KH, Leong KF, Chua CK, Du ZH, Cheah CM. Characterization of SLS parts for drug delivery devices. Rapid Prototyp J. 2001;7(5):262–7.

    Article  Google Scholar 

  51. Goyanes A, Buanz AB, Basit AW, Gaisford S. Fused-filament 3D printing (3DP) for fabrication of tablets. Int J Pharm. 2014;476(1–2):88–92.

    Article  CAS  PubMed  Google Scholar 

  52. 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 : Off J Eur Fed Pharm Sci. 2015;68:11–7.

    Article  CAS  Google Scholar 

  53. Sandler N, Salmela I, Fallarero A, Rosling A, Khajeheian M, Kolakovic R, et al. Towards fabrication of 3D printed medical devices to prevent biofilm formation. Int J Pharm. 2014;459(1–2):62–4.

    Article  CAS  PubMed  Google Scholar 

  54. Weisman JA, Nicholson JC, Tappa K, Jammalamadaka U, Wilson CG, Mills DK. Antibiotic and chemotherapeutic enhanced three-dimensional printer filaments and constructs for biomedical applications. Int J Nanomedicine. 2015;10:357–70.

    PubMed  PubMed Central  Google Scholar 

  55. Moulton SE, Wallace GG. 3-dimensional (3D) fabricated polymer based drug delivery systems. J Control Release. 2014;193:27–34.

    Article  CAS  PubMed  Google Scholar 

  56. 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.

    Article  CAS  PubMed  Google Scholar 

  57. 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(2):643–50.

    Article  CAS  PubMed  Google Scholar 

  58. 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.

    Article  CAS  PubMed  Google Scholar 

  59. Melchels FPW, Feijen J, Grijpma DW. A review on stereolithography and its applications in biomedical engineering. Biomaterials. 2010;31(24):6121–30.

    Article  CAS  PubMed  Google Scholar 

  60. Cooke MN, Fisher JP, Dean D, Rimnac C, Mikos AG. Use of stereolithography to manufacture critical-sized 3D biodegradable scaffolds for bone ingrowth. J Biomed Mater Res B Appl Biomater. 2003;64(2):65–9.

    Article  PubMed  CAS  Google Scholar 

  61. Lan PX, Lee JW, Seol YJ, Cho DW. Development of 3D PPF/DEF scaffolds using micro-stereolithography and surface modification. J Mater Sci Mater Med. 2009;20(1):271–9.

    Article  CAS  PubMed  Google Scholar 

  62. Liska R, Schuster M, Inführ R, Turecek C, Fritscher C, Seidl B, et al. Photopolymers for rapid prototyping. J Coat Technol Res. 2007;4(4):505–10.

    Article  CAS  Google Scholar 

  63. Lu Y, Chen S. Projection printing of 3-dimensional tissue scaffolds. Methods Mol Biol (Clifton, NJ). 2012;868:289–302.

    Article  CAS  Google Scholar 

  64. Melchels FP, Feijen J, Grijpma DW. A poly(D, L-lactide) resin for the preparation of tissue engineering scaffolds by stereolithography. Biomaterials. 2009;30(23–24):3801–9.

    Article  CAS  PubMed  Google Scholar 

  65. McMains S. Layered manufacturing technologies. Commun ACM. 2005;48(6):50–6.

    Article  Google Scholar 

  66. Chua CK, Leong KF, An J. 1 - Introduction to rapid prototyping of biomaterials. In: Narayan R, editor. Rapid Prototyping of Biomaterials: Woodhead Publishing; 2014. p. 1–15.

  67. Suzuki M, Sawa T, Terada Y, Takahashi T, Aoyagi S. Fabrication of microneedles precisely imitating mosquito’s proboscis by nanoscale tree dimensional laser lithography and its characterization. In.Transducers 2015; 2015. p. 121–124.

  68. Skoog SA, Goering PL, Narayan RJ. Stereolithography in tissue engineering. J Mater Sci Mater Med. 2014;25(3):845–56.

    Article  CAS  PubMed  Google Scholar 

  69. Popov VK, Evseev AV, Ivanov AL, Roginski VV, Volozhin AI, Howdle SM. Laser stereolithography and supercritical fluid processing for custom-designed implant fabrication. J Mater Sci Mater Med. 2004;15(2):123–8.

    Article  CAS  PubMed  Google Scholar 

  70. Formlabs. Form 1+ high-resolution 3D printer. 6/11/2015. Available from: http://formlabs.com/products/form-1-plus/.

  71. Tumbleston JR, Shirvanyants D, Ermoshkin N, Janusziewicz R, Johnson AR, Kelly D, et al. Continuous liquid interface production of 3D objects. Science. 2015;347(6228):1349–52.

    Article  CAS  PubMed  Google Scholar 

  72. Aprecia. Zipdose® technology. 12/3/2015. Available from: https://aprecia.com/zipdose-platform/zipdose-technology.php.

  73. Seitz H, Rieder W, Irsen S, Leukers B, Tille C. Three-dimensional printing of porous ceramic scaffolds for bone tissue engineering. J Biomed Mater Res B Appl Biomater. 2005;74B(2):782–8.

    Article  CAS  Google Scholar 

  74. Sun Y, Soh S. Printing tablets with fully customizable release profiles for personalized medicine. Adv Mater (Deerfield Beach, Fla). 2015;27(47):7847–53.

    Article  CAS  Google Scholar 

  75. Pyrce Lewis WE, Rowe CW, Cima MJ, Materna PA. System and method for uniaxial compression of an article, such as a three-dimensionally printed dosage form. In.: Patent 0198677; 2011.

  76. Wang CC, Tejwani Motwani MR, Roach WJ, Kay JL, Yoo J, Surprenant HL, et al. Development of near zero-order release dosage forms using three-dimensional printing (3-DP) technology. Drug Dev Ind Pharm. 2006;32(3):367–76.

    Article  CAS  PubMed  Google Scholar 

  77. Schmidt M, Pohle D, Rechtenwald T. Selective laser sintering of PEEK. CIRP Ann Manuf Technol. 2007;56(1):205–8.

    Article  Google Scholar 

  78. Hunt JA, Callaghan JT, Sutcliffe CJ, Morgan RH, Halford B, Black RA. The design and production of Co–Cr alloy implants with controlled surface topography by CAD–CAM method and their effects on osseointegration. Biomaterials. 2005;26(29):5890–7.

    Article  CAS  PubMed  Google Scholar 

  79. Traini T, Mangano C, Sammons RL, Mangano F, Macchi A, Piattelli A. Direct laser metal sintering as a new approach to fabrication of an isoelastic functionally graded material for manufacture of porous titanium dental implants. Dent Mater. 2008;24(11):1525–33.

    Article  CAS  PubMed  Google Scholar 

  80. Mangano C, Piattelli A, d’Avila S, Iezzi G, Mangano F, Onuma T, et al. Early human bone response to laser metal sintering surface topography: a histologic report. J Oral Implantol. 2010;36(2):91–6.

    Article  PubMed  Google Scholar 

  81. Kang H, Long JP, Urbiel Goldner GD, Goldstein SA, Hollister SJ. A paradigm for the development and evaluation of novel implant topologies for bone fixation: implant design and fabrication. J Biomech. 2012;45(13):2241–7.

    Article  PubMed  Google Scholar 

  82. Bae EJ, Kim HY, Kim WC, Kim JH. In vitro evaluation of the bond strength between various ceramics and cobalt-chromium alloy fabricated by selective laser sintering. J Adv Prosthodont. 2015;7(4):312–6.

    Article  PubMed  PubMed Central  Google Scholar 

  83. Ding R, Wu Z, Qiu G, Wu G, Wang H, Su X, et al. Selective Laser Sintering-produced porous titanium alloy scaffold for bone tissue engineering. Zhonghua Yi Xue Za Zhi. 2014;94(19):1499–502.

    CAS  PubMed  Google Scholar 

  84. Xie F, He X, Lu X, Cao S, Qu X. Preparation and properties of porous Ti-10Mo alloy by selective laser sintering. Mater Sci Eng C Mater Biol Appl. 2013;33(3):1085–90.

    Article  CAS  PubMed  Google Scholar 

  85. Wendel B, Rietzel D, Kühnlein F, Feulner R, Hülder G, Schmachtenberg E. Additive processing of polymers. Macromol Mater Eng. 2008;293(10):799–809.

    Article  CAS  Google Scholar 

  86. Van Hooreweder B, Moens D, Boonen R, Kruth J-P, Sas P. On the difference in material structure and fatigue properties of nylon specimens produced by injection molding and selective laser sintering. Polym Test. 2013;32(5):972–81.

    Article  CAS  Google Scholar 

  87. Tan KH, Chua CK, Leong KF, Cheah CM, Cheang P, Abu Bakar MS, et al. Scaffold development using selective laser sintering of polyetheretherketone–hydroxyapatite biocomposite blends. Biomaterials. 2003;24(18):3115–23.

    Article  CAS  PubMed  Google Scholar 

  88. Williams JM, Adewunmi A, Schek RM, Flanagan CL, Krebsbach PH, Feinberg SE, et al. Bone tissue engineering using polycaprolactone scaffolds fabricated via selective laser sintering. Biomaterials. 2005;26(23):4817–27.

    Article  CAS  PubMed  Google Scholar 

  89. Bertrand P, Bayle F, Combe C, Goeuriot P, Smurov I. Ceramic components manufacturing by selective laser sintering. Appl Surf Sci. 2007;254(4):989–92.

    Article  CAS  Google Scholar 

  90. Rombouts M, Kruth JP, Froyen L, Mercelis P. Fundamentals of selective laser melting of alloyed steel powders. CIRP Ann Manuf Technol. 2006;55(1):187–92.

    Article  Google Scholar 

  91. Wong KV, Hernandez A. A review of additive manufacturing. ISRN Mech Eng. 2012;2012:10.

    Article  Google Scholar 

  92. Goyanes A, Martinez PR, Buanz A, Basit AW, Gaisford S. Effect of geometry on drug release from 3D printed tablets. Int J Pharm. 2015;494(2):657–63.

    Article  CAS  PubMed  Google Scholar 

  93. Pietrzak K, Isreb A, Alhnan MA. A flexible-dose dispenser for immediate and extended release 3D printed tablets. Eur J Pharm Biopharm. 2015;96:380–7.

    Article  CAS  PubMed  Google Scholar 

  94. Rattanakit P, Moulton SE, Santiago KS, Liawruangrath S, Wallace GG. Extrusion printed polymer structures: a facile and versatile approach to tailored drug delivery platforms. Int J Pharm. 2012;422(1–2):254–63.

    Article  CAS  PubMed  Google Scholar 

  95. Gbureck U, Vorndran E, Mueller FA, Barralet JE. Low temperature direct 3D printed bioceramics and biocomposites as drug release matrices. J Control Release. 2007;122(2):173–80.

    Article  CAS  PubMed  Google Scholar 

  96. Wu C, Luo Y, Cuniberti G, Xiao Y, Gelinsky M. Three-dimensional printing of hierarchical and tough mesoporous bioactive glass scaffolds with a controllable pore architecture, excellent mechanical strength and mineralization ability. Acta Biomater. 2011;7(6):2644–50.

    Article  CAS  PubMed  Google Scholar 

  97. Jacob J, Coyle N, West TG, Monkhouse DC, Jain NB. Rapid disperse dosage form containing levetiracetam. In.: Patent US20140271862 A1; 2014.

  98. Wu W, Zheng Q, Guo X, Huang W. The controlled-releasing drug implant based on the three dimensional printing technology: Fabrication and properties of drug releasing in vivo. J Wuhan Univ Technol. 2009;24(6):977–81.

    Article  CAS  Google Scholar 

  99. Maier A-K, Dezmirean L, Will J, Greil P. Three-dimensional printing of flash-setting calcium aluminate cement. J Mater Sci. 2011;46(9):2947–54.

    Article  CAS  Google Scholar 

  100. Cheah CM, Leong KF, Chua CK, Low KH, Quek HS. Characterization of microfeatures in selective laser sintered drug delivery devices. Proc Inst Mech Eng H. 2002;216(H6):369–83.

    Article  CAS  PubMed  Google Scholar 

  101. Leong KF, Chua CK, Gui WS, Verani. Building porous biopolymeric microstructures for controlled drug delivery devices using selective laser sintering. Int J Adv Manuf Technol. 2006;31(5–6):483–9.

    Article  Google Scholar 

  102. 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 Tec. 2015;30(Part B):360–7.

    Article  CAS  Google Scholar 

  103. Masood SH. Application of fused deposition modelling in controlled drug delivery devices. Assem Autom. 2007;27(3):215–21.

    Article  Google Scholar 

  104. Petrak M, Rogers L. Antimicrobial articles produced by additive manufacturing. In.: Google Patents; 2014.

  105. Goyanes A, Wang J, Buanz A, Martinez-Pacheco R, Telford R, Gaisford S, et al. 3D printing of medicines: engineering novel oral devices with unique design and drug release characteristics. Mol Pharm. 2015;12(11):4077–84.

    Article  CAS  PubMed  Google Scholar 

  106. Spence JD. Polypill: for pollyanna*. Int J Stroke. 2008;3(2):92–7.

    Article  PubMed  Google Scholar 

  107. Lewanczuk R, Tobe SW. More medications, fewer pills: combination medications for the treatment of hypertension. Can J Cardiol. 2007;23(7):573–6.

    Article  PubMed  PubMed Central  Google Scholar 

  108. Charan J, Goyal JP, Saxena D. Effect of Pollypill on cardiovascular parameters: systematic review and meta-analysis. J Cardiovasc Dis Res. 2013;4(2):92–7.

    Article  PubMed  PubMed Central  Google Scholar 

  109. Yu DG, Zhu L-M, Branford-White CJ, Yang XL. Three-dimensional printing in pharmaceutics: promises and problems. J Pharm Sci. 2008;97(9):3666–90.

    Article  CAS  PubMed  Google Scholar 

  110. Ursan ID, Chiu L, Pierce A. Three-dimensional drug printing: a structured review. J Am Pharm Assoc (2003). 2013;53(2):136–44.

    Article  Google Scholar 

  111. Huang SH, Liu P, Mokasdar A, Hou L. Additive manufacturing and its societal impact: a literature review. Int J Adv Manuf Technol. 2013;67(5–8):1191–203.

    Article  Google Scholar 

  112. Pham DT, Gault RS. A comparison of rapid prototyping technologies. Int J Mach Tool Manuf. 1998;38(10–11):1257–87.

    Article  Google Scholar 

  113. Gaylo CM, Pryor TJ, Fairweather JA, Weitzel DE. Apparatus, systems and methods for use in three-dimensional printing. In.: Google Patents; 2006.

  114. Skelton J. Fused deposition modeling. 15/10/51. Available from: http://3d-print.blogspot.com/2008/02/fused-deposition-modelling.html.

  115. Katstra WE, Palazzolo RD, Rowe CW, Giritlioglu B, Teung P, Cima MJ. Oral dosage forms fabricated by Three Dimensional Printing (TM). J Control Release. 2000;66(1):1–9.

    Article  CAS  PubMed  Google Scholar 

  116. Fuh JYH, Lu L, Tan CC, Shen ZX, Chew S. Processing and characterising photo-sensitive polymer in the rapid prototyping process. J Mater Process Technol. 1999;89–90:211–7.

    Article  Google Scholar 

  117. Rowe CW, Katstra WE, Palazzolo RD, Giritlioglu B, Teung P, Cima MJ. Multimechanism oral dosage forms fabricated by three dimensional printing. J Control Release. 2000;66(1):11–7.

    Article  CAS  PubMed  Google Scholar 

  118. Outterson K. Regulating compounding pharmacies after NECC. N Engl J Med. 2012;367(21):1969–72.

    Article  CAS  PubMed  Google Scholar 

  119. Drues M. The case of the New England Compounding Center. Healthcare packaging. 8/11/15. Available from: http://www.healthcarepackaging.com/case-new-england-compounding-center.

  120. Sun L. FDA finds widespread safety issues at compounding pharmacies. In.Washington Post: Health & Science; 2013.

  121. Colleen D, Lisa B, Matthew J, Farah T, James B, Gail D, Celeste L, MadaganKevin, MaidenTodd, Tracy Q, John S. 3D printing of medical devices: when a novel technology meets traditional legal principles. Reedsmith. 9/12/15. Available from: http://www.reedsmith.com/3D-Printing-of-Medical-Devices--When-a-Novel-Technology-Meets-Traditional-Legal-Principles-09-09-2015/.

  122. Drues M. Printing medical devices at home is just the beginning: Part II. 8/12/15. Available from: http://www.healthcarepackaging.com/trends-and-issues/3d-printingadditive-manufacturing/printing-medical-devices-home-just-beginning.

  123. Sparrow N. FDA tackles opportunities, challenges of 3D-printed medical devices. In.Plastics today: Medicine; 2014.

  124. Pollack S, Coburn J. FDA goes 3-D. 30/11/15. Available from: http://blogs.fda.gov/fdavoice/index.php/tag/osel/.

  125. FDA. Proposed guidance development and focused retrospective review of final guidance. 15/12/15 Available from: http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/Overview/MDUFAIII/ucm321367.htm#complete.

  126. Drues M. 3D printed pill: formulate, download, and print your own medicine? AAPS webinars. 2/12/15. Available from: https://www.aaps.org/eLearning/Webinars/2015/3D_Printed_Pill/.

  127. Jacobson M. The regulatory and legal implications of 3D printing. In.MDT: Medical design technology; 2015.

  128. FDA. Establishment registration and device listing for manufacturers and initial importers of devices. 15/12/15.

  129. Zopf DA, Hollister SJ, Nelson ME, Ohye RG, Green GE. Bioresorbable airway splint created with a three-dimensional printer. N Engl J Med. 2013;368(21):2043–5.

    Article  CAS  PubMed  Google Scholar 

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ACKNOWLEDGMENTS AND DISCLOSURES

The authors would like to thank UCLAN Innovation Team for this support and Mrs Reem Arafat for her help with graphics design.

M A Alhnan is the innovator in pending UK patent applications P218530GB1 and P227819GB in the field of 3D printing of medicines.

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Authors and Affiliations

  1. School of Pharmacy and Biomedical Sciences, University of Central Lancashire, Preston, PR1 2HE, Lancashire, UK

    Mohamed A. Alhnan, Tochukwu C. Okwuosa, Muzna Sadia, Ka-Wai Wan & Basel Arafat

  2. School of Medicine, University of Central Lancashire, Preston, Lancashire, UK

    Waqar Ahmed

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  1. Mohamed A. Alhnan
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  2. Tochukwu C. Okwuosa
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  3. Muzna Sadia
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Correspondence to Mohamed A. Alhnan.

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Alhnan, M.A., Okwuosa, T.C., Sadia, M. et al. Emergence of 3D Printed Dosage Forms: Opportunities and Challenges. Pharm Res 33, 1817–1832 (2016). https://doi.org/10.1007/s11095-016-1933-1

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  • DOI: https://doi.org/10.1007/s11095-016-1933-1

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