Advertisement

The Shape of Things to Come: Emerging Applications of 3D Printing in Healthcare

  • Sarah J. Trenfield
  • Christine M. Madla
  • Abdul W. Basit
  • Simon Gaisford
Chapter
Part of the AAPS Advances in the Pharmaceutical Sciences Series book series (AAPS, volume 31)

Abstract

We now stand on the brink of a fourth industrial revolution. By the remarkable technological advancements of the twenty-first century, manufacturing is now becoming digitalised. In the last decade, the rise of rapid prototyping has provided individual patient care, acted as an educational and training tool and contributed to research. Innovative technologies such as three-dimensional printing (3DP), have the potential to cause a paradigm shift in medicine design, manufacture and use. Instead of using conventional large batch processes, customised printlets (3D printed tablets) with a tailored dose, shape, size and release characteristics could be produced on-demand. Arguably, never before has the pharmaceutical industry experienced such a transformative technology in medicines manufacture. Indeed, this technology could be utilised throughout the drug development process, ranging from pre-clinical development and first-in-human clinical trials through to front-line medical care (personalized medicines). This chapter aims to discuss the current and future potential applications of 3DP in healthcare and, ultimately, the power of 3DP in pharmaceuticals.

Keywords

3D printing Additive manufacturing Pharmaceutics Bioprinting Drug delivery systems Digital health 

References

  1. 1.
    Morgan J. What is the fourth industrial revolution? Forbes. 2016.; Available from: https://www.forbes.com/sites/jacobmorgan/2016/02/19/what-is-the-4th-industrialrevolution/# 65e28c00f392
  2. 2.
    Chowdhry A. What can 3D printing do? Here are 6 creative examples. Forbes. 2013.; Available from: https://www.forbes.com/sites/amitchowdhry/2013/10/08/what-can-3dprinting- do-here-are-6-creative-examples/
  3. 3.
    Sahlgren C, Meinander A, Zhang H, Cheng F, Preis M, Xu C, Salminen TA, Toivola D, Abankwa D, Rosling A, Şen Karaman D, Salo-Ahen OMH, Österbacka R, Eriksson JE, Willför S, Petre I, Peltonen J, Leino R, Johnson M, Rosenholm J, Sandler N. Tailored approaches in drug development and diagnostics: from molecular design to biological model systems. Adv Healthc Mater. 2017;6(21):1700258.CrossRefGoogle Scholar
  4. 4.
    Miller JS, Stevens KR, Yang MT, Baker BM, Nguyen DH, Cohen DM, et al. Rapid casting of patterned vascular networks for perfusable engineered three-dimensional tissues. Nat Mater. 2012;11(9):768–74.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Leukers B, Gulkan H, Irsen SH, Milz S, Tille C, Schieker M, et al. Hydroxyapatite scaffolds for bone tissue engineering made by 3D printing. J Mater Sci Mater Med. 2005;16(12):1121–4.CrossRefGoogle Scholar
  6. 6.
    Ventola CL. Medical applications for 3D printing: current and projected uses. Pharmacy and Therapeutics. 2014;39(10):704–11.PubMedPubMedCentralGoogle Scholar
  7. 7.
    Aprecia Pharmaceutials. 3D printing - ZipDose technology. 2015. Available from: https://aprecia.com/zipdose-platform/3d-printing.php.
  8. 8.
    Muwaffak Z, Goyanes A, Clark V, Basit AW, Hilton ST, Gaisford S. Patient-specific 3D scanned and 3D printed antimicrobial polycaprolactone wound dressings. Int J Pharm. 2017;527(1–2):161–70.CrossRefPubMedGoogle Scholar
  9. 9.
    Goyanes A, Det-Amornrat U, Wang J, Basit AW, Gaisford S. 3D scanning and 3D printing as innovative technologies for fabricating personalized topical drug delivery systems. J Control Release. 2016;234:41–8.CrossRefPubMedGoogle Scholar
  10. 10.
    Waran V, Pancharatnam D, Thambinayagam HC, Raman R, Rathinam AK, Balakrishnan YK, et al. The utilization of cranial models created using rapid prototyping techniques in the development of models for navigation training. J Neurol Surg A Cent Eur Neurosurg. 2014;75(1):12–5.PubMedGoogle Scholar
  11. 11.
    Li J, Nie L, Li Z, Lin L, Tang L, Ouyang J. Maximizing modern distribution of complex anatomical spatial information: 3D reconstruction and rapid prototype production of anatomical corrosion casts of human specimens. Anat Sci Educ. 2012;5(6):330–9.CrossRefPubMedGoogle Scholar
  12. 12.
    Nakada T, Akiba T, Inagaki T, Morikawa T. Thoracoscopic anatomical subsegmentectomy of the right S2b + S3 using a 3D printing model with rapid prototyping. Interact Cardiovasc Thorac Surg. 2014;19(4):696–8.CrossRefPubMedGoogle Scholar
  13. 13.
    Rengier F, Mehndiratta A, von Tengg-Kobligk H, Zechmann CM, Unterhinninghofen R, Kauczor HU, et al. 3D printing based on imaging data: review of medical applications. Int J Comput Assist Radiol Surg. 2010;5(4):335–41.CrossRefPubMedGoogle Scholar
  14. 14.
    Mendoza HR. Researches study the 3D printing of surgical instruments for use in long space missions. 3DPrint.com. 2014. Available from: https://3dprint.com/8937/3dprinting-space-missions/.
  15. 15.
    Saunders S. Wrist osteotomy guide. 3DPrint.Com. 2017. Available from: https://www.3dprint.com/165853/materialise-mimics-wrist-osteotomy/wrist-osteotomy-guide/.
  16. 16.
    Wyman C. Some straight talk (and a Round Award) for 3D printing in orthodontics. Stratasys. 2014. Available from: http://blog.stratasys.com/2014/02/28/dental-orthodontics- 3d-printer/.
  17. 17.
    Trenfield SJ, Awad A, Goyanes A, Gaisford S, Basit AW. 3D printing pharmaceuticals: drug development to front-line care. Trends Pharmacol Sci. 2018; 39(5):440–451.Google Scholar
  18. 18.
    Peng W, Datta P, Ayan B, Ozbolat V, Sosnoski D, Ozbolat IT. 3D bioprinting for drug discovery and development in pharmaceutics. Acta Biomater. 2017;57:26–46.CrossRefPubMedGoogle Scholar
  19. 19.
    Collins FS, Varmus H. A new initiative on precision medicine. N Engl J Med. 2015;372(9):793–5.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Alomari M, Mohamed FH, Basit AW, Gaisford S. Personalised dosing: printing a dose of one’s own medicine. Int J Pharm. 2015;494(2):568–77.CrossRefPubMedGoogle Scholar
  21. 21.
    Freire AC, Basit AW, Choudhary R, Piong CW, Merchant HA. Does sex matter? The influence of gender on gastrointestinal physiology and drug delivery. Int J Pharm. 2011;415(1–2):15–28.CrossRefPubMedGoogle Scholar
  22. 22.
    Merchant HA, Liu F, Orlu Gul M, Basit AW. Age-mediated changes in the gastrointestinal tract. Int J Pharm 2016;512(2):382–95.Google Scholar
  23. 23.
    Hamburg MA, Collins FS. The path to personalized medicine. N Engl J Med. 2010;363(4):301–4.CrossRefPubMedGoogle Scholar
  24. 24.
    Hatton GB, Madla CM, Rabbie SC, Basit AW. All disease begins in the gut: Influence of gastrointestinal disorders and surgery on oral drug performance. Int J Pharm. 2018;548(1):408–22.Google Scholar
  25. 25.
    Yadav V, Varum F, Bravo R, Furrer E, Bojic D, Basit AW. Inflammatory bowel disease: exploring gut physiology for novel therapeutic targets. Transl Res. 2016;176:38–68.Google Scholar
  26. 26.
    Taherali F, Varum F, Basit AW. A slippery slope: on the origin, role and physiology of mucus. Adv Drug Deliv Rev. 2018;124:16–33.CrossRefPubMedGoogle Scholar
  27. 27.
    FDA. Paving the way for personalized medicine. 2013. Available from: https://www.fda.gov/downloads/ScienceResearch/SpecialTopics/PersonalizedMedicine/UCM372421.pdf.
  28. 28.
    Awad A, Trenfield SJ, Goyanes A, Gaisford S, Basit AW. Reshaping drug development using 3D printing. Drug Discov Today. 2018;  https://doi.org/10.1016/j.drudis.2018.05.025.
  29. 29.
    Kearns GL, Abdel-Rahman SM, Alander SW, Blowey DL, Leeder JS, Kauffman RE. Developmental pharmacology--drug disposition, action, and therapy in infants and children. N Engl J Med. 2003;349(12):1157–67.CrossRefGoogle Scholar
  30. 30.
    Breitkreutz J, Boos J. Paediatric and geriatric drug delivery. Expert Opin Drug Deliv. 2007;4(1):37–45.CrossRefPubMedGoogle Scholar
  31. 31.
    Peek BT, Al-Achi A, Coombs SJ. Accuracy of tablet splitting by elderly patients. JAMA. 2002;288(4):451–2.CrossRefPubMedGoogle Scholar
  32. 32.
    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.CrossRefPubMedGoogle Scholar
  33. 33.
    McDevitt JT, Gurst AH, Chen Y. Accuracy of tablet splitting. Pharmacother: J Hum Pharmacol Drug Ther. 1998;18(1):193–7.Google Scholar
  34. 34.
    Hill S, 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.PubMedGoogle Scholar
  35. 35.
    Okwuosa TC, Pereira BC, Arafat B, Cieszynska M, Isreb A, Alhnan MA. Fabricating a shell-core delayed release tablet using dual FDM 3D printing for patient-centred therapy. Pharm Res. 2017;34(2):427–37.CrossRefPubMedGoogle Scholar
  36. 36.
    Okwuosa TC, Stefaniak D, Arafat B, Isreb A, Wan K-W, Alhnan MA. A lower temperature FDM 3D printing for the manufacture of patient-specific immediate release tablets. Pharm Res. 2016;33(11):2704–12.CrossRefPubMedGoogle Scholar
  37. 37.
    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.CrossRefPubMedGoogle Scholar
  38. 38.
    Goyanes A, Chang H, Sedough D, Hatton GB, Wang J, Buanz A, et al. Fabrication of controlled-release budesonide tablets via desktop (FDM) 3D printing. Int J Pharm. 2015;496(2):414–20.CrossRefPubMedGoogle Scholar
  39. 39.
    Maher RL, Hanlon J, Hajjar ER. Clinical consequences of polypharmacy in elderly. Expert Opin Drug Saf. 2014;13(1):57–65.CrossRefPubMedGoogle Scholar
  40. 40.
    Murray MD, Kroenke K. Polypharmacy and medication adherence: small steps on a long road. J Gen Intern Med. 2001;16(2):137–9.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    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.CrossRefPubMedGoogle Scholar
  42. 42.
    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.CrossRefPubMedGoogle Scholar
  43. 43.
    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.CrossRefPubMedGoogle Scholar
  44. 44.
    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.CrossRefPubMedGoogle Scholar
  45. 45.
    Gioumouxouzis CI, Katsamenis OL, Bouropoulos N, Fatouros DG. 3D printed oral solid dosage forms containing hydrochlorothiazide for controlled drug delivery. J Drug Deliv Sci Technol. 2017;40:164–71.CrossRefGoogle Scholar
  46. 46.
    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.CrossRefPubMedGoogle Scholar
  47. 47.
    Goyanes A, Fina F, Martorana A, Sedough D, Gaisford S, Basit AW. Development of modified release 3D printed tablets (printlets) with pharmaceutical excipients using additive manufacturing. Int J Pharm. 2017;527(1–2):21–30.CrossRefPubMedGoogle Scholar
  48. 48.
    Fina F, Madla CM, Goyanes A, Zhang J, Gaisford S, Basit AW. Fabricating 3D printed orally disintegrating printlets using selective laser sintering. Int J Pharm. 2018;541(1–2):101–7.CrossRefPubMedGoogle Scholar
  49. 49.
    Martinez PR, Goyanes A, Basit AW, Gaisford S. Fabrication of drug-loaded hydrogels with stereolithographic 3D printing. Int J Pharm. 2017;532(1):313–7.CrossRefPubMedGoogle Scholar
  50. 50.
    Beck RCR, Chaves PS, Goyanes A, Vukosavljevic B, Buanz A, Windbergs M, Basit AW, Gaisford S. 3D printed tablets loaded with polymeric nanocapsules: an innovative approach to produce customized drug delivery systems. Int J Pharm. 2017;528(1–2):268–79.CrossRefPubMedGoogle Scholar
  51. 51.
    Goyanes A, Kobayashi M, Martínez-Pacheco R, Gaisford S, Basit AW. Fused-filament 3D printing of drug products: microstructure analysis and drug release characteristics of PVA-based caplets. Int J Pharm. 2016;514(1):290–5.CrossRefPubMedGoogle Scholar
  52. 52.
    Wang J, Goyanes A, Gaisford S, Basit AW. Stereolithographic (SLA) 3D printing of oral modified-release dosage forms. Int J Pharm. 2016;503(1–2):207–12.CrossRefPubMedGoogle Scholar
  53. 53.
    Kollamaram G, Croker DM, Walker GM, Goyanes A, Basit AW, Gaisford S. Low temperature fused deposition modeling (FDM) 3D printing of thermolabile drugs. Int J Pharm. 2018;545(1–2):144–52.CrossRefPubMedGoogle Scholar
  54. 54.
    Sadia M, Arafat B, Ahmed W, Forbes RT, Alhnan MA. Channelled tablets: an innovative approach to accelerating drug release from 3D printed tablets. J Control Release. 2018;269:355–63.CrossRefPubMedGoogle Scholar
  55. 55.
    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;  https://doi.org/10.1208/s12249-018-1075-3.
  56. 56.
    Maroni A, Melocchi A, Parietti F, Foppoli A, Zema L, Gazzaniga A. 3D printed multi-compartment capsular devices for two-pulse oral drug delivery. J Control Release. 2017;268:10–8.CrossRefPubMedGoogle Scholar
  57. 57.
    Solanki NG, Tahsin M, Shah AW, Serajuddin ATM. 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. 2018;107(1):390–401.CrossRefPubMedGoogle Scholar
  58. 58.
    Fina F, Goyanes A, Madla CM, Awad A, Trenfield SJ, Kuek JM, Patel P, Gaisford S, Basit AW. 3D printing of drug-loaded gyroid lattices using selective laser sintering. Int J Pharm. 2018;  https://doi.org/10.1016/j.ijpharm.2018.05.044.
  59. 59.
    Goyanes A, Robles Martinez P, Buanz A, Basit AW, Gaisford S. Effect of geometry on drug release from 3D printed tablets. Int J Pharm. 2015;494(2):657–63.CrossRefPubMedGoogle Scholar
  60. 60.
    Fina F, Goyanes A, Gaisford S, Basit AW. Selective laser sintering (SLS) 3D printing of medicines. Int J Pharm. 2017;529(1-2):285–93.CrossRefPubMedGoogle Scholar
  61. 61.
    Diment LE, Thompson MS, Bergmann JHM. Clinical efficacy and effectiveness of 3D printing: a systematic review. BMJ Open. 2017;7(12):e016891.CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    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.CrossRefPubMedGoogle Scholar
  63. 63.
    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.CrossRefPubMedGoogle Scholar
  64. 64.
    Jamróz W, Kurek M, Łyszczarz E, Szafraniec J, Knapik-Kowalczuk J, Syrek K, et al. 3D printed orodispersible films with Aripiprazole. Int J Pharm. 2017;533:413–20.CrossRefPubMedGoogle Scholar
  65. 65.
    Vuddanda PR, Alomari M, Dodoo CC, Trenfield SJ, Velga S, Basit AW, Gaisford S. Personalisation of warfarin therapy using thermal ink-jet printing. Eur J Pharm Sci. 2018;117:80–7.CrossRefPubMedGoogle Scholar
  66. 66.
    Goyanes A, Scarpa M, Kamlow M, Gaisford S, Basit AW, Orlu M. Patient acceptability of 3D printed medicines. Int J Pharm. 2017;530(1):71–8.CrossRefPubMedGoogle Scholar
  67. 67.
    Kommanaboyina B, Rhodes CT. Trends in stability testing, with emphasis on stability during distribution and storage. Drug Dev Ind Pharm. 1999;25(7):857–68.CrossRefPubMedGoogle Scholar
  68. 68.
    eMC. Persantin retard 200 mg (Dipyridamole). 2015. Available from: https://www.medicines.org.uk/emc/medicine/304-SHELF_LIFE.
  69. 69.
    Norman J, Madurawe RD, Moore CM, Khan MA, Khairuzzaman A. A new chapter in pharmaceutical manufacturing: 3D-printed drug products. Adv Drug Deliv Rev. 2017;108:39–50.CrossRefPubMedGoogle Scholar
  70. 70.
    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.CrossRefPubMedGoogle Scholar
  71. 71.
    Hay M, Thomas DW, Craighead JL, Economides C, Rosenthal J. Clinical development success rates for investigational drugs. Nat Biotechnol. 2014;32(1):40–51.CrossRefPubMedGoogle Scholar
  72. 72.
    Gao Y, Gesenberg C, Zheng W. Chapter 17 – Oral formulations for preclinical studies: principle, design, and development considerations A2 – Qiu, Yihong. In: Chen Y, Zhang GGZ, Yu L, Mantri RV, editors. Developing solid oral dosage forms. 2nd ed. Boston: Academic Press; 2017. p. 455–95.CrossRefGoogle Scholar
  73. 73.
    Dorato MA, Engelhardt JA. The no-observed-adverse-effect-level in drug safety evaluations: use, issues, and definition(s). Regul Toxicol Pharmacol. 2005;42(3):265–74.CrossRefPubMedGoogle Scholar
  74. 74.
    FDA. Estimating the maximum safe starting dose in initial clinical trials for therapeutics in adult healthy volunteers. 2005. Available from: https://www.fda.gov/downloads/drugs/guidances/ucm078932.pdf.
  75. 75.
    Hatton GB, Yadav V, Basit AW, Merchant HA. Animal farm: considerations in animal gastrointestinal physiology and relevance to drug delivery in humans. J Pharm Sci. 2015;104(9):2747–76.CrossRefPubMedGoogle Scholar
  76. 76.
    Buoen C, Bjerrum OJ, Thomsen MS. How first-time-in-human studies are being performed: a survey of phase I dose-escalation trials in healthy volunteers published between 1995 and 2004. J Clin Pharmacol. 2005;45(10):1123–36.CrossRefPubMedGoogle Scholar
  77. 77.
    Ku MS, Dulin W. A biopharmaceutical classification-based right-first-time formulation approach to reduce human pharmacokinetic variability and project cycle time from first-in-human to clinical proof-of-concept. Pharm Dev Technol. 2012;17(3):285–302.CrossRefPubMedGoogle Scholar
  78. 78.
    Tong G, Wang J-S, Sverdlov O, Huang S-P, Slemmon R, Croop R, et al. Multicenter, randomized, double-blind, placebo-controlled, single-ascending dose study of the oral γ-secretase inhibitor BMS-708163 (Avagacestat): tolerability profile, pharmacokinetic parameters, and pharmacodynamic markers. Clin Ther. 2012;34(3):654–67.CrossRefPubMedGoogle Scholar
  79. 79.
    ABPI. First in human studies: points to consider in study placement, design and conduct. 2011. Available from: http://www.abpi.org.uk/ourwork/ library/guidelines/Documents/First in Human Studies.pdf.
  80. 80.
    Capretto L, Byrne G, Trenfield SJ, Dowden L, Booth S. Formulation, analytical and regulatory strategies for first-in-human clinical trials. Oral formulation roadmap from early drug discovery to development. Hoboken: Wiley; 2017. p. 165–241.Google Scholar
  81. 81.
    Mahajan R, Gupta K. Adaptive design clinical trials: methodology, challenges and prospect. Indian J Pharm. 2010;42(4):201–7.CrossRefGoogle Scholar
  82. 82.
    Perlstein I, Bolognese JA, Krishna R, Wagner JA. Evaluation of agile designs in first-in-human (FIH) trials—a simulation study. AAPS J. 2009;11(4):653.CrossRefPubMedPubMedCentralGoogle Scholar
  83. 83.
    EUPATI. New approaches to clinical trials: adaptive designs. 2015. Available from: https://www.eupati.eu/clinical-development-and-trials/new-approaches-to-clinical-trialsadaptive- designs/-Adaptive_designs.
  84. 84.
    Brennan Z. CROs slowly shifting to adaptive clinical trial designs outsourcing pharma. 2013. Available from: http://www.outsourcing-pharma.com/Clinical-Development/CROs- Slowly-Shifting-to-Adaptive-Clinical-Trial-Designs.
  85. 85.
    Hariharan M, Ganorkar L, Amidon G, Cavallo A, Gatti P, Hageman MJ, et al. Reducing the time to develop and manufacture formulations for first oral dose in humans. Pharm Technol. 2003.; Available from: http://www.capsugel.com/media/library/reducing_the_time_to_develop_and_manufacture_formulations_for_first_oral_dose_in_humans.pdf
  86. 86.
    Kuentz M, Holm R, Elder DP. Methodology of oral formulation selection in the pharmaceutical industry. Eur J Pharm Sci. 2016;87:136–63.CrossRefPubMedGoogle Scholar
  87. 87.
    Goyanes A, Buanz ABM, Basit AW, Gaisford S. Fused-filament 3D printing (3DP) for fabrication of tablets. Int J Pharm. 2014;476(1):88–92.CrossRefPubMedGoogle Scholar
  88. 88.
    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.CrossRefPubMedGoogle Scholar
  89. 89.
    Stratasys. How 3D printing will continue to transform manufacturing. Stratasys Direct. 2015. Available from: https://www.stratasysdirect.com/content/white_papers/str_7463_15_sdm_wp_transform_mfg.pdf.
  90. 90.
    Awad A, Trenfield SJ, Gaisford S, Basit AW. 3D printed medicines: A new branch of digital healthcare. Int J Pharm. 2018;548(1):586–96.Google Scholar
  91. 91.
    Zema L, Melocchi A, Maroni A, Gazzaniga A. Three-dimensional printing of medicinal products and the challenge of personalized therapy. J Pharm Sci. 2017;106(7):1697–705.CrossRefPubMedGoogle Scholar
  92. 92.
    Shah AK, Agnihotri SA. Recent advances and novel strategies in pre-clinical formulation development: an overview. J Control Release. 2011;156(3):281–96.CrossRefPubMedGoogle Scholar
  93. 93.
    Goyanes A, Fernández-Ferreiro A, Majeed A, Gomez-Lado N, Awad A, Luaces-Rodríguez A, Gaisford S, Aguiar P, Basit AW. PET/CT imaging of 3D printed devices in the gastrointestinal tract of rodents. Int J Pharm. 2018;536(1):158–64.CrossRefPubMedGoogle Scholar
  94. 94.
    Ayad MH. Rational formulation strategy from drug discovery profiling to human proof of concept. Drug Deliv. 2015;22(6):877–84.CrossRefPubMedGoogle Scholar
  95. 95.
    Dobry DE, Settell DM, Baumann JM, Ray RJ, Graham LJ, Beyerinck RA. A model-based methodology for spray-drying process development. J Pharm Innov. 2009;4(3):133–42.CrossRefPubMedPubMedCentralGoogle Scholar
  96. 96.
    Breitenbach J. Melt extrusion: from process to drug delivery technology. Eur J Pharm Biopharm. 2002;54(2):107–17.CrossRefPubMedGoogle Scholar
  97. 97.
    Tiwari RV, Patil H, Repka MA. Contribution of hot-melt extrusion technology to advance drug delivery in the 21st century. Expert Opin Drug Deliv. 2016;13(3):451–64.CrossRefPubMedGoogle Scholar
  98. 98.
    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.CrossRefPubMedGoogle Scholar
  99. 99.
    Le Tourneau C, Lee JJ, Siu LL. Dose escalation methods in phase I cancer clinical trials. JNCI J Natl Canc Inst. 2009;101(10):708–20.CrossRefGoogle Scholar
  100. 100.
    Page SJ, Persch AC. Recruitment, retention, and blinding in clinical trials. Am J Occup Ther. 2013;67(2):154–61.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2018

Authors and Affiliations

  • Sarah J. Trenfield
    • 1
  • Christine M. Madla
    • 1
  • Abdul W. Basit
    • 1
    • 2
  • Simon Gaisford
    • 1
    • 2
  1. 1.Department of Pharmaceutics, UCL School of PharmacyUniversity College LondonLondonUK
  2. 2.FabRx Ltd.Ashford, KentUK

Personalised recommendations