The Digital Pharmacies Era: How 3D Printing Technology Using Fused Deposition Modeling Can Become a Reality

Pharmaceutics - Tập 11 Số 3 - Trang 128
Maisa R. P. Araújo1, Lívia L. Sá‐Barreto1, Taís Gratieri1, Guilherme M. Gelfuso1, Marcílio Cunha‐Filho1
1Laboratory of Food, Drugs and Cosmetics (LTMAC), University of Brasília (UnB), Brasília 70910-900, Brazil

Tóm tắt

The pharmaceutical industry is set to join the fourth industrial revolution with the 3D printing of medicines. The application of 3D printers in compounding pharmacies will turn them into digital pharmacies, wrapping up the telemedicine care cycle and definitively modifying the pharmacotherapeutic treatment of patients. Fused deposition modeling 3D printing technology melts extruded drug-loaded filaments into any dosage form; and allows the obtainment of flexible dosages with different shapes, multiple active pharmaceutical ingredients and modulated drug release kinetics—in other words, offering customized medicine. This work aimed to present an update on this technology, discussing its challenges. The co-participation of the pharmaceutical industry and compounding pharmacies seems to be the best way to turn this technology into reality. The pharmaceutical industry can produce drug-loaded filaments on a large scale with the necessary quality and safety guarantees; while digital pharmacies can transform the filaments into personalized medicine according to specific prescriptions. For this to occur, adaptations in commercial 3D printers will need to meet health requirements for drug products preparation, and it will be necessary to make advances in regulatory gaps and discussions on patent protection. Thus, despite the conservatism of the sector, 3D drug printing has the potential to become the biggest technological leap ever seen in the pharmaceutical segment, and according to the most optimistic prognostics, it will soon be within reach.

Từ khóa


Tài liệu tham khảo

Trenfield, 2018, 3D printed drug products: Non-destructive dose verification using a rapid point-and-shoot approach, Int. J. Pharm., 549, 283, 10.1016/j.ijpharm.2018.08.002

Liang, 2018, 3D printing of a wearable personalized oral delivery device: A first-in-human study, Sci. Adv., 4, eaat2544, 10.1126/sciadv.aat2544

Fu, 2018, 3D printing of vaginal rings with personalized shapes for controlled release of progesterone, Int. J. Pharm., 539, 75, 10.1016/j.ijpharm.2018.01.036

Muwaffak, 2017, Patient-specific 3D scanned and 3D printed antimicrobial polycaprolactone wound dressings, Int. J. Pharm., 527, 161, 10.1016/j.ijpharm.2017.04.077

Goyanes, 2016, 3D scanning and 3D printing as innovative technologies for fabricating personalized topical drug delivery systems, J. Control. Release, 234, 41, 10.1016/j.jconrel.2016.05.034

Goyanes, 2017, Patient acceptability of 3D printed medicines, Int. J. Pharm., 530, 71, 10.1016/j.ijpharm.2017.07.064

Goyanes, 2015, Effect of geometry on drug release from 3D printed tablets, Int. J. Pharm., 494, 657, 10.1016/j.ijpharm.2015.04.069

Okwuosa, 2017, Fabricating a shell-core delayed release tablet using dual FDM 3D printing for patient-centred therapy, Pharm. Res., 34, 427, 10.1007/s11095-016-2073-3

Gioumouxouzis, 2018, A 3D printed bilayer oral solid dosage form combining metformin for prolonged and glimepiride for immediate drug delivery, Eur. J. Pharm. Sci., 120, 40, 10.1016/j.ejps.2018.04.020

Zhang, 2017, Hydroxypropyl methylcellulose-based controlled release dosage by melt extrusion and 3D printing: Structure and drug release correlation, Carbohydr. Polym., 177, 49, 10.1016/j.carbpol.2017.08.058

Goyanes, 2017, Development of modified release 3D printed tablets (printlets) with pharmaceutical excipients using additive manufacturing, Int. J. Pharm., 527, 21, 10.1016/j.ijpharm.2017.05.021

Goyanes, 2014, Fused-filament 3D printing (3DP) for fabrication of tablets, Int. J. Pharm., 476, 88, 10.1016/j.ijpharm.2014.09.044

Bloomquist, 2018, Controlling release from 3D printed medical devices using CLIP and drug-loaded liquid resins, J. Control. Release, 278, 9, 10.1016/j.jconrel.2018.03.026

Ventola, 2014, Medical applications for 3D printing: Current and projected uses, Pharm. Ther., 39, 704

Norman, 2017, A new chapter in pharmaceutical manufacturing: 3D-printed drug products, Adv. Drug Deliv. Rev., 108, 39, 10.1016/j.addr.2016.03.001

Hsiao, 2018, 3D printing of oral drugs: A new reality or hype?, Expert Opin. Drug Deliv., 15, 1, 10.1080/17425247.2017.1371698

Awad, 2018, Reshaping drug development using 3D printing, Drug Discov. Today, 23, 1547, 10.1016/j.drudis.2018.05.025

James, 2009, Incidence, type and causes of dispensing errors: A review of the literature, Int. J. Pharm. Pract., 17, 9, 10.1211/ijpp.17.1.0004

Palo, 2017, 3D printed drug delivery devices: Perspectives and technical challenges, Expert Rev. Med. Devices, 14, 685, 10.1080/17434440.2017.1363647

Lim, 2018, 3D printed drug delivery and testing systems—A passing fad or the future?, Adv. Drug Deliv. Rev., 132, 139, 10.1016/j.addr.2018.05.006

Trenfield, 2018, 3D Printing Pharmaceuticals: Drug Development to Frontline Care, Trends Pharmacol. Sci., 39, 440, 10.1016/j.tips.2018.02.006

Gelfuso, 2017, FDM 3D printing of modified drug-delivery systems using hot melt extrusion: A new approach for individualized therapy, Ther. Deliv., 8, 957, 10.4155/tde-2017-0067

Tan, D.K., Maniruzzaman, M., and Nokhodchi, A. (2018). Advanced Pharmaceutical Applications of Hot-Melt Extrusion Coupled with Fused Deposition Modelling (FDM) 3D Printing for Personalised Drug Delivery. Pharmaceutics, 10.

Long, 2017, Application of fused deposition modelling (FDM) method of 3D printing in drug delivery, Curr. Pharm. Des., 23, 433, 10.2174/1381612822666161026162707

Prasad, 2016, 3D Printing technologies for drug delivery: A review, Drug. Dev. Ind. Pharm., 42, 1019, 10.3109/03639045.2015.1120743

Moulton, 2014, 3-dimensional (3D) fabricated polymer based drug-delivery systems, J. Control. Rel., 193, 27, 10.1016/j.jconrel.2014.07.005

Szafraniec, 2018, 3D Printing in Pharmaceutical and Medical Applications—Recent Achievements and Challenges, Pharm. Res., 35, 176, 10.1007/s11095-018-2454-x

Basit, 2018, The Shape of Things to Come: Emerging Applications of 3D Printing in Healthcare, 3D Printing of Pharmaceuticals, Volume 31, 1, 10.1007/978-3-319-90755-0_1

Pravin, 2018, Integration of 3D printing with dosage forms: A new perspective for modern healthcare, Biomed. Pharmacother., 107, 146, 10.1016/j.biopha.2018.07.167

Sadia, 2016, Adaptation of pharmaceutical excipients to FDM 3D printing for the fabrication of patient-tailored immediate release tablets, Int. J. Pharm., 513, 659, 10.1016/j.ijpharm.2016.09.050

Arafat, 2018, 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, 10.1016/j.ejpb.2018.04.010

Chai, 2017, Fused Deposition Modeling (FDM) 3D Printed Tablets for Intragastric Floating Delivery of Domperidone, Sci. Rep., 7, 2829, 10.1038/s41598-017-03097-x

Goyanes, 2015, 3D printing of medicines: Engineering novel oral devices with unique design and drug release characteristics, Mol. Pharm., 12, 4077, 10.1021/acs.molpharmaceut.5b00510

Kempin, 2018, Immediate Release 3D-Printed Tablets Produced Via Fused Deposition Modeling of a Thermo-Sensitive Drug, Pharm. Res., 35, 124, 10.1007/s11095-018-2405-6

Arafat, 2018, 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, 10.1016/j.ejps.2018.03.019

Scoutaris, 2018, 3D Printed “Starmix” Drug Loaded Dosage Forms for Paediatric Applications, Pharm. Res., 35, 34, 10.1007/s11095-017-2284-2

Maroni, 2017, 3D printed multi-compartment capsular devices for two-pulse oral drug delivery, J. Control. Release, 268, 10, 10.1016/j.jconrel.2017.10.008

Melocchi, 2018, Industrial Development of a 3D-Printed Nutraceutical Delivery Platform in the Form of a Multicompartment HPC Capsule, AAPS. PharmSciTech, 19, 3343, 10.1208/s12249-018-1029-9

Smith, 2018, Pharmaceutical 3D printing: Design and qualification of a single step print and fill capsule, Int. J. Pharm., 544, 21, 10.1016/j.ijpharm.2018.03.056

Okwuosa, 2018, On demand manufacturing of patient-specific liquid capsules via co-ordinated 3D printing and liquid dispensing, Eur. J. Pharm. Sci., 118, 134, 10.1016/j.ejps.2018.03.010

Gioumouxouzis, 2017, 3D printed oral solid dosage forms containing hydrochlorothiazide for controlled drug delivery, J. Drug. Deliv. Sci. Technol., 40, 164, 10.1016/j.jddst.2017.06.008

Kurek, 2017, 3D printed orodispersible films with Aripiprazole, Int. J. Pharm., 533, 413, 10.1016/j.ijpharm.2017.05.052

Luzuriaga, 2018, Biodegradable 3D printed polymer microneedles for transdermal drug delivery, Lab. Chip, 18, 1223, 10.1039/C8LC00098K

Davies, 2017, On drug base incompatibilities during extrudate manufacture and fused deposition 3D printing, J. 3D Print. Med., 1, 31, 10.2217/3dp-2016-0006

Genina, 2016, Ethylene vinyl acetate (EVA) as a new drug carrier for 3D printed medical drug delivery devices, Eur. J. Pharm. Sci., 90, 53, 10.1016/j.ejps.2015.11.005

Fu, 2018, Combination of 3D printing technologies and compressed tablets for preparation of riboflavin floating tablet-in-device (TiD) systems, Int. J. Pharm., 549, 370, 10.1016/j.ijpharm.2018.08.011

Genina, 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, 10.1016/j.jconrel.2017.10.003

Goyanes, 2018, PET/CT imaging of 3D printed devices in the gastrointestinal tract of rodents, Int. J. Pharm., 536, 158, 10.1016/j.ijpharm.2017.11.055

Feuerbach, 2018, Characterisation of fused deposition modeling 3D printers for pharmaceutical and medical applications, Pharm. Dev. Technol., 23, 1136, 10.1080/10837450.2018.1492618

Alhijjaj, 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, 10.1016/j.ejpb.2016.08.016

Goyanes, 2015, 3D printing of modified-release aminosalicylate (4-ASA and 5-ASA) tablets, Eur. J. Pharm. Biopharm., 89, 157, 10.1016/j.ejpb.2014.12.003

Kollamaram, 2018, Low temperature fused deposition modeling (FDM) 3D printing of thermolabile drugs, Int. J. Pharm., 545, 144, 10.1016/j.ijpharm.2018.04.055

Melocchi, 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, 10.1016/j.jddst.2015.07.016

Markl, 2017, Analysis of 3D Prints by X-ray Computed Microtomography and Terahertz Pulsed Imaging, Pharm. Res., 34, 1037, 10.1007/s11095-016-2083-1

Landin, 2012, Temperature-sensitive gels for intratumoral delivery of β-lapachone: Effect of cyclodextrins and ethanol, Sci. World J., 2012, 126723

Awad, 2018, 3D printed medicines: A new branch of digital healthcare, Int. J. Pharm., 548, 586, 10.1016/j.ijpharm.2018.07.024

Skowyra, 2015, Fabrication of extended-release patient-tailored prednisolone tablets via fused deposition modelling (FDM) 3D printing, Eur. J. Pharm. Sci., 68, 11, 10.1016/j.ejps.2014.11.009

Trivedi, 2018, Additive manufacturing of pharmaceuticals for precision medicine applications: A review of the promises and perils in implementation, Addit. Manuf., 23, 319

Gelfuso, 2017, Evolution of quality on pharmaceutical design: Regulatory requirement?, Accred. Qual. Assur., 22, 199, 10.1007/s00769-017-1270-z

Korte, 2018, Formulation development and process analysis of drug-loaded filaments manufactured via hot-melt extrusion for 3D-printing of medicines, Pharm. Dev. Technol., 23, 1117, 10.1080/10837450.2018.1433208

Verstraete, 2018, 3D printing of high drug loaded dosage forms using thermoplastic polyurethanes, Int. J. Pharm., 536, 318, 10.1016/j.ijpharm.2017.12.002

Sadia, 2018, Channelled tablets: An innovative approach to accelerating drug release from 3D printed tablets, J. Control. Release, 269, 355, 10.1016/j.jconrel.2017.11.022

Weisman, 2015, Antibiotic and chemotherapeutic enhanced three-dimensional printer filaments and constructs for biomedical applications, Int. J. Nanomed., 10, 357

Pietrzak, 2015, A flexible-dose dispenser for immediate and extended release 3D printed tablets, Eur. J. Pharm. Biopharm., 96, 380, 10.1016/j.ejpb.2015.07.027

Goyanes, 2016, Fused-filament 3D printing of drug products: Microstructure analysis and drug release characteristics of PVA-based caplets, Int. J. Pharm., 514, 290, 10.1016/j.ijpharm.2016.06.021

Melocchi, 2016, Hot-melt extruded filaments based on pharmaceutical grade polymers for 3D printing by fused deposition modeling, Int. J. Pharm., 509, 255, 10.1016/j.ijpharm.2016.05.036

Okwuosa, 2016, A lower temperature FDM 3D printing for the manufacture of patient-specific immediate release tablets, Pharm. Res., 33, 2704, 10.1007/s11095-016-1995-0

Coburn, 2016, Additively manufactured medical products—The FDA perspective, 3D Print Med., 2, 1, 10.1186/s41205-016-0005-9

Basit, 2018, 3D printing technologies, implementation and regulation: An overview, 3D Printing of Pharmaceuticals, Volume 31, 21, 10.1007/978-3-319-90755-0_2

Economidou, 2018, 3D printing applications for transdermal drug delivery, Int. J. Pharm., 544, 415, 10.1016/j.ijpharm.2018.01.031

Alhnan, 2016, Emergence of 3D printed dosage forms: Opportunities and challenges, Pharm. Res., 33, 1817, 10.1007/s11095-016-1933-1

Jose, 2018, 3D printing of pharmaceuticals—A potential technology in developing personalized medicine, Asian J. Pharm. Dev., 6, 46, 10.22270/ajprd.v6i3.375

Zema, 2017, Three-Dimensional Printing of Medicinal Products and the Challenge of Personalized Therapy, J Pharm Sci., 106, 1697, 10.1016/j.xphs.2017.03.021

Stones, 2017, 3D printing of pharmaceuticals: Patent and regulatory challenges, Pharm. Pat. Anal., 6, 145, 10.4155/ppa-2017-0017

Souza, 2009, The Compounding Pharmacy in Brazil: A Pharmacist’s Perspective, Int. J. Pharm. Compd., 13, 87

Karpiński, T.M. (2018). Selected Medicines Used in Iontophoresis. Pharmaceutics, 10.