Polymers for Extrusion-Based 3D Printing of Pharmaceuticals: A Holistic Materials–Process Perspective

Pharmaceutics - Tập 12 Số 2 - Trang 124
Mohammad Azad1, Deborah Olawuni1, Georgia Kimbell1, Abu Zayed Md Badruddoza2, Md. Shahadat Hossain3, Tasnim Sultana4
1Department of Chemical, Biological and Bioengineering, North Carolina A&T State University, Greensboro, NC 27411, USA
2Department of Chemical and Life Sciences Engineering, Virginia Commonwealth University, Richmond, VA 23284, USA
3Department of Engineering Technology, Queensborough Community College, City University of New York (CUNY), Bayside, NY 11364, USA
4Department of Public Health, School of Arts and Sciences, Massachusetts College of Pharmacy and Health Sciences (MCPHS), Boston, MA 02115, USA

Tóm tắt

Three dimensional (3D) printing as an advanced manufacturing technology is progressing to be established in the pharmaceutical industry to overcome the traditional manufacturing regime of 'one size fits for all'. Using 3D printing, it is possible to design and develop complex dosage forms that can be suitable for tuning drug release. Polymers are the key materials that are necessary for 3D printing. Among all 3D printing processes, extrusion-based (both fused deposition modeling (FDM) and pressure-assisted microsyringe (PAM)) 3D printing is well researched for pharmaceutical manufacturing. It is important to understand which polymers are suitable for extrusion-based 3D printing of pharmaceuticals and how their properties, as well as the behavior of polymer–active pharmaceutical ingredient (API) combinations, impact the printing process. Especially, understanding the rheology of the polymer and API–polymer mixtures is necessary for successful 3D printing of dosage forms or printed structures. This review has summarized a holistic materials–process perspective for polymers on extrusion-based 3D printing. The main focus herein will be both FDM and PAM 3D printing processes. It elaborates the discussion on the comparison of 3D printing with the traditional direct compression process, the necessity of rheology, and the characterization techniques required for the printed structure, drug, and excipients. The current technological challenges, regulatory aspects, and the direction toward which the technology is moving, especially for personalized pharmaceuticals and multi-drug printing, are also briefly discussed.

Từ khóa


Tài liệu tham khảo

Ligon, 2017, Polymers for 3D printing and customized additive manufacturing, Chem. Rev., 117, 10212, 10.1021/acs.chemrev.7b00074

Hofmann, 2014, 3D printing gets a boost and opportunities with polymer materials, ACS Macro Lett., 3, 382, 10.1021/mz4006556

Vikram Singh, A., Hasan Dad Ansari, M., Wang, S., Laux, P., Luch, A., Kumar, A., Patil, R., and Nussberger, S. (2019). The Adoption of Three-Dimensional Additive Manufacturing from Biomedical Material Design to 3D Organ Printing. Appl. Sci., 9.

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

Liaw, 2017, Current and emerging applications of 3D printing in medicine, Biofabrication, 9, 024102, 10.1088/1758-5090/aa7279

Yoo, J., Bradbury, T.J., Bebb, T.J., Iskra, J., Surprenant, H.L., and West, T.G. (2014). Three-Dimensional Printing System and Equipment Assembly. (US8888480B2), U.S. Patent.

Ginsburg, 2001, Personalized medicine: Revolutionizing drug discovery and patient care, Trends Biotechnol., 19, 491, 10.1016/S0167-7799(01)01814-5

Schork, 2015, Personalized medicine: Time for one-person trials, Nature, 520, 609, 10.1038/520609a

Yu, 2008, Three-Dimensional Printing in Pharmaceutics: Promises and Problems, J. Pharm. Sci., 97, 3666, 10.1002/jps.21284

Sachs, 1992, Three dimensional printing: Rapid tooling and prototypes directly from a CAD model, J. Manuf. Sci. Eng., 114, 481

Goole, 2016, 3D printing in pharmaceutics: A new tool for designing customized drug delivery systems, Int. J. Pharm., 499, 376, 10.1016/j.ijpharm.2015.12.071

Wu, 1996, Solid free-form fabrication of drug delivery devices, J. Control. Release, 40, 77, 10.1016/0168-3659(95)00173-5

Rowe, 2000, Multimechanism oral dosage forms fabricated by three dimensional printing™, J. Control. Release, 66, 11, 10.1016/S0168-3659(99)00224-2

Wang, 2006, Development of near zero-order release dosage forms using three-dimensional printing (3-DP™) technology, Drug Dev. Ind. Pharm., 32, 367, 10.1080/03639040500519300

Yu, 2007, Tablets with material gradients fabricated by three-dimensional printing, J. Pharm. Sci., 96, 2446, 10.1002/jps.20864

Infanger, 2019, Powder bed 3D-printing of highly loaded drug delivery devices with hydroxypropyl cellulose as solid binder, Int. J. Pharm., 555, 198, 10.1016/j.ijpharm.2018.11.048

Khaled, 2014, Desktop 3D printing of controlled release pharmaceutical bilayer tablets, Int. J. Pharm., 461, 105, 10.1016/j.ijpharm.2013.11.021

Khaled, 2015, 3D printing of five-in-one dose combination polypill with defined immediate and sustained release profiles, J. Control. Release, 217, 308, 10.1016/j.jconrel.2015.09.028

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

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

Chen, 2020, Preparation and In vitro Evaluation of FDM 3D-Printed Ellipsoid-Shaped Gastric Floating Tablets with Low Infill Percentages, AAPS PharmSciTech, 21, 6, 10.1208/s12249-019-1521-x

Alhijjaj, M., Nasereddin, J., Belton, P., and Qi, S. (2019). Impact of Processing Parameters on the Quality of Pharmaceutical Solid Dosage Forms Produced by Fused Deposition Modeling (FDM). Pharmaceutics, 11.

Eleftheriadis, 2019, Unidirectional drug release from 3D printed mucoadhesive buccal films using FDM technology: In vitro and ex vivo evaluation, Eur. J. Pharm. Biopharm., 144, 180, 10.1016/j.ejpb.2019.09.018

Viidik, 2019, 3D-printability of aqueous poly(ethylene oxide) gels, Eur. Polym. J., 120, 109206, 10.1016/j.eurpolymj.2019.08.033

Feuerbach, 2018, Development of filaments for fused deposition modeling 3D printing with medical grade poly(lactic-co-glycolic acid) copolymers, Pharm. Dev. Technol., 24, 487, 10.1080/10837450.2018.1514522

Nukala, 2019, Abuse Deterrent Immediate Release Egg-Shaped Tablet (Egglets) Using 3D Printing Technology: Quality by Design to Optimize Drug Release and Extraction, AAPS PharmSciTech, 20, 80, 10.1208/s12249-019-1298-y

Healy, A.V., Fuenmayor, E., Doran, P., Geever, L.M., Higginbotham, C.L., and Lyons, J.G. (2019). Additive Manufacturing of Personalized Pharmaceutical Dosage Forms via Stereolithography. Pharmaceutics, 11.

Martinez, 2018, Influence of Geometry on the Drug Release Profiles of Stereolithographic (SLA) 3D-Printed Tablets, AAPS PharmSciTech, 19, 3355, 10.1208/s12249-018-1075-3

Wang, 2016, Stereolithographic (SLA) 3D printing of oral modified-release dosage forms, Int. J. Pharm., 503, 207, 10.1016/j.ijpharm.2016.03.016

Awad, A., Fina, F., Trenfield, S.J., Patel, P., Goyanes, A., Gaisford, S., and Basit, A.W. (2019). 3D Printed Pellets (Miniprintlets): A Novel, Multi-Drug, Controlled Release Platform Technology. Pharmaceutics, 11.

Fina, 2018, Fabricating 3D printed orally disintegrating printlets using selective laser sintering, Int. J. Pharm., 541, 101, 10.1016/j.ijpharm.2018.02.015

Fina, 2017, Selective laser sintering (SLS) 3D printing of medicines, Int. J. Pharm., 529, 285, 10.1016/j.ijpharm.2017.06.082

Kyobula, 2017, 3D inkjet printing of tablets exploiting bespoke complex geometries for controlled and tuneable drug release, J. Control. Release, 261, 207, 10.1016/j.jconrel.2017.06.025

Clark, 2017, 3D printing of tablets using inkjet with UV photoinitiation, Int. J. Pharm., 529, 523, 10.1016/j.ijpharm.2017.06.085

Cader, 2019, Water-based 3D inkjet printing of an oral pharmaceutical dosage form, Int. J. Pharm., 564, 359, 10.1016/j.ijpharm.2019.04.026

Kadry, 2019, Digital light processing (DLP) 3D-printing technology and photoreactive polymers in fabrication of modified-release tablets, Eur. J. Pharm. Sci., 135, 60, 10.1016/j.ejps.2019.05.008

2019, Hydrophilic excipients in digital light processing (DLP) printing of sustained release tablets: Impact on internal structure and drug dissolution rate, Int. J. Pharm., 572, 118790, 10.1016/j.ijpharm.2019.118790

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

Godwin, 2001, New strategies for polymer development in pharmaceutical science—A short review, J. Pharm. Pharmacol., 53, 1175, 10.1211/0022357011776612

Jones, D.S. (2004). Pharmaceutical Applications of Polymers for Drug Delivery, Rapra Technology Ltd.

Park, 2019, Pharmaceutical applications of 3D printing technology: Current understanding and future perspectives, J. Pharm. Investig., 49, 575

Souto, 2019, 3D printing in the design of pharmaceutical dosage forms, Pharm. Dev. Technol., 24, 1044, 10.1080/10837450.2019.1630426

Araújo, M.R.P., Sa-Barreto, L.L., Gratieri, T., Gelfuso, G.M., and Cunha-Filho, M. (2019). The Digital Pharmacies Era: How 3D Printing Technology Using Fused Deposition Modeling Can Become a Reality. Pharmaceutics, 11.

Mohammed, 2018, Advanced Pharmaceutical Applications of Hot-Melt Extrusion Coupled with Fused Deposition Modelling (FDM) 3D Printing for Personalised Drug Delivery, Pharmaceutics, 10, 203, 10.3390/pharmaceutics10040203

Kjar, A., and Huang, Y. (2019). Application of Micro-Scale 3D Printing in Pharmaceutics. Pharmaceutics, 11.

Gioumouxouzis, 2019, Recent advances in pharmaceutical dosage forms and devices using additive manufacturing technologies, Drug Discov. Today, 24, 636, 10.1016/j.drudis.2018.11.019

Aimar, 2019, The Role of 3D Printing in Medical Applications: A State of the Art, J. Health Eng., 2019, 5340616, 10.1155/2019/5340616

Vithani, 2019, An Overview of 3D Printing Technologies for Soft Materials and Potential Opportunities for Lipid-based Drug Delivery Systems, Pharm. Res., 36, 4, 10.1007/s11095-018-2531-1

Joo, Y., Shin, I., Ham, G., Abuzar, S.M., Hyun, S.-M., and Hwang, S.-J. (2019). The advent of a novel manufacturing technology in pharmaceutics: Superiority of fused deposition modeling 3D printer. J. Pharm. Investig., 1–15.

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

He, 2016, A review of 3D printing via fused deposition modeling in pharmaceutics, Acta Pharm. Sin., 51, 1659

Konta, A.A., García-Piña, M., and Serrano, D.R. (2017). Personalised 3D printed medicines: Which techniques and polymers are more successful?. Bioengineering, 4.

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

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

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

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

Firth, J., Basit, A.W., and Gaisford, S. (2018). The role of semi-solid extrusion printing in clinical practice. 3D Printing of Pharmaceuticals, Springer.

Szafraniec, 2018, 3D Printing in Pharmaceutical and Medical Applications—Recent Achievements and Challenges, Pharm. Res., 35, 1

Ehtezazi, 2018, The Application of 3D Printing in the Formulation of Multilayered Fast Dissolving Oral Films, J. Pharm. Sci., 107, 1076, 10.1016/j.xphs.2017.11.019

Zidan, 2019, Extrudability analysis of drug loaded pastes for 3D printing of modified release tablets, Int. J. Pharm., 554, 292, 10.1016/j.ijpharm.2018.11.025

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

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

Tagami, 2019, Fabrication of Naftopidil-Loaded Tablets Using a Semisolid Extrusion-Type 3D Printer and the Characteristics of the Printed Hydrogel and Resulting Tablets, J. Pharm. Sci., 108, 907, 10.1016/j.xphs.2018.08.026

Capel, 2018, 3D printing for chemical, pharmaceutical and biological applications, Nat. Rev. Chem., 2, 422, 10.1038/s41570-018-0058-y

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

Azad, 2018, A compact, portable, re-configurable, and automated system for on-demand pharmaceutical tablet manufacturing, Int. J. Pharm., 539, 157, 10.1016/j.ijpharm.2018.01.027

Azad, 2019, On-Demand Manufacturing of Direct Compressible Tablets: Can Formulation Be Simplified?, Pharm. Res., 36, 167, 10.1007/s11095-019-2716-2

Maniruzzaman, M. (2019). Pharmaceutical Applications of Hot-Melt Extrusion: Continuous Manufacturing, Twin-Screw Granulations, and 3D Printing. Pharmaceutics, 11.

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

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

Zhang, 2017, Coupling 3D printing with hot-melt extrusion to produce controlled-release tablets, Int. J. Pharm., 519, 186, 10.1016/j.ijpharm.2016.12.049

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

Saviano, 2019, Poly (vinyl alcohol) 3D printed tablets: The effect of polymer particle size on drug loading and process efficiency, Int. J. Pharm., 561, 1, 10.1016/j.ijpharm.2019.02.025

Pereira, 2019, ‘Temporary Plasticiser’: A novel solution to fabricate 3D printed patient-centred cardiovascular ‘Polypill’architectures, Eur. J. Pharm. Biopharm., 135, 94, 10.1016/j.ejpb.2018.12.009

Balogh, 2019, 3D Floating tablets: Appropriate 3d design from the perspective of different in vitro dissolution testing methodologies, Int. J. Pharm., 567, 118433, 10.1016/j.ijpharm.2019.06.024

Khaled, 2015, 3D printing of tablets containing multiple drugs with defined release profiles, In. J. Pharm., 494, 643

Goyanes, 2019, Hydroxypropyl-β-cyclodextrin-based fast dissolving carbamazepine printlets prepared by semisolid extrusion 3D printing, Carbohydr. Polym., 221, 55, 10.1016/j.carbpol.2019.05.084

Corporation, T.L. (2019, December 29). Carbopol® Polymer Products. Available online: https://www.lubrizol.com/Life-Sciences/Products/Carbopol-Polymer-Products.

Corporation, T.L. (2019, December 29). Carbopol® 971P NF Polymer. Available online: https://www.lubrizol.com/en/Life-Sciences/Products/Carbopol-Polymer-Products/Carbopol-971P-NF-Polymer.

Corporation, T.L. (2019, December 29). Carbopol® 974P NF Polymer. Available online: https://www.lubrizol.com/Life-Sciences/Products/Carbopol-Polymer-Products/Carbopol-974P-NF-Polymer.

Cellulosics, D. (2005). ETHOCEL™: Ethylcellulose Polymers Technical Handbook, TDC Company.

Kempin, 2017, Assessment of different polymers and drug loads for fused deposition modeling of drug loaded implants, Eur. J. Pharm. Biopharm., 115, 84, 10.1016/j.ejpb.2017.02.014

Thakral, 2013, Eudragit®: A technology evaluation, Exp. Opin. Drug Deliv., 10, 131, 10.1517/17425247.2013.736962

Evonik (2019, December 22). Eudragit® Setting Benchmarks in Oral Solid Dosage Forms Since 1954. Available online: https://healthcare.evonik.com/sites/lists/NC/DocumentsHC/Evonik-Eudragit_brochure.pdf.

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

2007, Physical mechanical and tablet formation properties of hydroxypropylcellulose: In pure form and in mixtures, AAPS PharmSciTech, 8, 82, 10.1208/pt0804092

Ashland Inc (2019, December 22). Klucel™ Hydroxypropylcellulose—Physical and Chemical Properties. Available online: https://www.ashland.com/file_source/Ashland/Product/Documents/Pharmaceutical/PC_11229_Klucel_HPC.pdf.

Li, 2005, The use of hypromellose in oral drug delivery, J. Pharm. Pharmacol., 57, 533, 10.1211/0022357055957

Siepmann, 2012, Modeling of drug release from delivery systems based on hydroxypropyl methylcellulose (HPMC), Adv. Drug Deliv. Rev., 64, 163, 10.1016/j.addr.2012.09.028

Ethers, M.C. (1997). Technical Handbook, Dow Chemical Company.

Concheiro, 2003, Chemical structure and glass transition temperature of non-ionic cellulose ethers, J. Therm. Anal. Calorim., 73, 587, 10.1023/A:1025434314396

Patlolla, 2010, Solvent-dependent properties of electrospun fibrous composites for bone tissue regeneration, Acta Biomater., 6, 90, 10.1016/j.actbio.2009.07.028

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

Ulery, 2011, Biomedical applications of biodegradable polymers, J. Polym. Sci. Part B, 49, 832, 10.1002/polb.22259

Gunatillake, 2006, Recent developments in biodegradable synthetic polymers, Biotechnol. Annu. Rev., 12, 301, 10.1016/S1387-2656(06)12009-8

Boetker, 2016, Modifying release characteristics from 3D printed drug-eluting products, Eur. J. Pharm. Sci., 90, 47, 10.1016/j.ejps.2016.03.013

Dwivedi, C., Pandey, H., Pandey, A.C., Patil, S., Ramteke, P.W., Laux, P., Luch, A., and Singh, A.V. (2019). In vivo biocompatibility of electrospun biodegradable dual carrier (antibiotic+ growth factor) in a mouse model—Implications for rapid wound healing. Pharmaceutics, 11.

Farah, 2016, Physical and mechanical properties of PLA, and their functions in widespread applications—A comprehensive review, Adv. Drug Deliv. Rev., 107, 367, 10.1016/j.addr.2016.06.012

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

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

Morita, 2000, Development of oral controlled release preparations, a PVA swelling controlled release system (SCRS): I. Design of SCRS and its release controlling factor, J. Control. Release, 63, 297, 10.1016/S0168-3659(99)00203-5

Gupta, 2011, Evolution of PVA gels prepared without crosslinking agents as a cell adhesive surface, J. Mater. Sci. Mater. Med., 22, 1763, 10.1007/s10856-011-4343-2

Poropat, 2019, Design and 3D printing of multi-compartmental PVA capsules for drug delivery, J. Drug Deliv. Sci., 52, 677

Haaf, 1985, Polymers of N-vinylpyrrolidone: Synthesis, characterization and uses, Polym. J., 17, 143, 10.1295/polymj.17.143

Sigma, M. (2019, December 20). Poly(ethylene glycol) and Poly(ethylene oxide). Available online: https://www.sigmaaldrich.com/materials-science/material-science-products.html?TablePage=20204110.

Pelras, T., Glass, S., Scherzer, T., Elsner, C., Schulze, A., and Abel, B. (2017). Transparent low molecular weight poly (ethylene glycol) diacrylate-based hydrogels as film media for photoswitchable drugs. Polymers, 9.

Hardung, 2010, Combining HME & solubilization: Soluplus®—The solid solution, Drug Deliv. Technol., 10, 20

Goyanes, 2015, Fabrication of controlled-release budesonide tablets via desktop (FDM) 3D printing, Int. J. Pharm., 496, 414, 10.1016/j.ijpharm.2015.10.039

Aho, 2015, Rheology as a tool for evaluation of melt processability of innovative dosage forms, Int. J. Pharm., 494, 623, 10.1016/j.ijpharm.2015.02.009

Yang, 2018, 3D printed tablets with internal scaffold structure using ethyl cellulose to achieve sustained ibuprofen release, Eur. J. Pharm. Sci., 115, 11, 10.1016/j.ejps.2018.01.005

Baumgart, 2000, Stiffness-an unknown world of mechanical science?, Injury, 31, 14, 10.1016/S0020-1383(00)80040-6

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

Lewis, 2004, Direct writing in three dimensions, Mater. Today, 7, 32, 10.1016/S1369-7021(04)00344-X

Rattanakit, 2012, Extrusion printed polymer structures: A facile and versatile approach to tailored drug delivery platforms, Int. J. Pharm., 422, 254, 10.1016/j.ijpharm.2011.11.007

Solanki, 2019, Effects of Surfactants on Itraconazole-Hydroxypropyl Methylcellulose Acetate Succinate Solid Dispersion Prepared by Hot Melt Extrusion. II: Rheological Analysis and Extrudability Testing, J. Pharm. Sci., 108, 3063, 10.1016/j.xphs.2019.05.010

Elbadawi, 2019, Rheological and Mechanical Investigation into the Effect of Different Molecular Weight Poly (ethylene glycol) s on Polycaprolactone-Ciprofloxacin Filaments, ACS Omega, 4, 5412, 10.1021/acsomega.8b03057

Polamaplly, 2019, 3D printing and characterization of hydroxypropyl methylcellulose and methylcellulose for biodegradable support structures, Polymer, 173, 119, 10.1016/j.polymer.2019.04.013

Suwardie, 2011, Rheological study of the mixture of acetaminophen and polyethylene oxide for hot-melt extrusion application, Eur. J. Pharm., 78, 506

Rahim, 2019, Recent Developments in Fused Deposition Modeling-Based 3D Printing of Polymers and Their Composites, Polym. Rev., 59, 589, 10.1080/15583724.2019.1597883

Tanner, 1983, Shear fracture in cone-plate rheometry, J. Rheol., 27, 47, 10.1122/1.549698

Cox, 1958, Correlation of dynamic and steady flow viscosities, J. Polym. Sci., 28, 619, 10.1002/pol.1958.1202811812

Cicala, G., Giordano, D., Tosto, C., Filippone, G., Recca, A., and Blanco, I. (2018). Polylactide (PLA) filaments a biobased solution for additive manufacturing: Correlating rheology and thermomechanical properties with printing quality. Materials, 11.

Yang, 2011, Determination of acetaminophen’s solubility in poly (ethylene oxide) by rheological, thermal and microscopic methods, Int. J. Pharm., 403, 83, 10.1016/j.ijpharm.2010.10.026

Hu, 2019, Facile preparation of bioactive nanoparticle/poly(ε-caprolactone) hierarchical porous scaffolds via 3D printing of high internal phase Pickering emulsions, J. Colloid Interface Sci., 545, 104, 10.1016/j.jcis.2019.03.024

Kim, 2019, Enhanced rheological behaviors of alginate hydrogels with carrageenan for extrusion-based bioprinting, J. Mech. Behav. Biomed. Mater., 98, 187, 10.1016/j.jmbbm.2019.06.014

Ibrahim, 2019, 3D Printing of Metformin HCl PVA Tablets by Fused Deposition Modeling: Drug Loading, Tablet Design, and Dissolution Studies, AAPS PharmSciTech, 20, 195, 10.1208/s12249-019-1400-5

Tagami, 2017, 3D printing factors important for the fabrication of polyvinylalcohol filament-based tablets, Biol. Pharm. Bull., 40, 357, 10.1248/bpb.b16-00878

Prasad, 2019, Development of a hot-melt extrusion (HME) process to produce drug loaded Affinisol™ 15LV filaments for fused filament fabrication (FFF) 3D printing, Addit. Manuf., 29, 100776

Zhang, 2019, 3D-Printed Isoniazid Tablets for the Treatment and Prevention of Tuberculosis—Personalized Dosing and Drug Release, AAPS PharmSciTech, 20, 52, 10.1208/s12249-018-1233-7

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

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

Sadia, 2018, From ‘fixed dose combinations’ to ‘a dynamic dose combiner’: 3D printed bi-layer antihypertensive tablets, Eur. J. Pharm. Sci., 123, 484, 10.1016/j.ejps.2018.07.045

Fuenmayor, E., Forde, M., Healy, A., Devine, D., Lyons, J., McConville, C., and Major, I. (2018). Material considerations for fused-filament fabrication of solid dosage forms. Pharmaceutics, 10.

Aho, J., Genina, N., Edinger, M., Botker, J.P., Baldursdottir, S., and Rantanen, J. (June, January 30). Drug-loaded poly (ε-caprolactone) for 3D printing of personalized medicine: A rheological study. Proceedings of the 25th Nordic Rheology Conference, Helsinki, Finland.

Isreb, 2019, 3D printed oral theophylline doses with innovative ‘radiator-like’design: Impact of polyethylene oxide (PEO) molecular weight, Int. J. Pharm., 564, 98, 10.1016/j.ijpharm.2019.04.017

Balogh, 2019, The applicability of pharmaceutical polymeric blends for the fused deposition modelling (FDM) 3D technique: Material considerations–printability–process modulation, with consecutive effects on in vitro release, stability and degradation, Eur. J. Pharm. Sci., 129, 110, 10.1016/j.ejps.2018.12.019

Solanki, 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, 10.1016/j.xphs.2017.10.021

Aho, 2017, The flow properties and presence of crystals in drug-polymer mixtures: Rheological investigation combined with light microscopy, Int. J. Pharm., 528, 383, 10.1016/j.ijpharm.2017.06.012

Zidan, 2019, Development of mechanistic models to identify critical formulation and process variables of pastes for 3D printing of modified release tablets, Int. J. Pharm., 555, 109, 10.1016/j.ijpharm.2018.11.044

Vervaet, 2017, Rheological characterization of molten polymer-drug dispersions as a predictive tool for pharmaceutical hot-melt extrusion processability, Pharm. Res., 34, 2312, 10.1007/s11095-017-2239-7

Gupta, 2016, Investigation of thermal and viscoelastic properties of polymers relevant to hot melt extrusion, IV: Affinisol™ HPMC HME polymers, AAPS PharmSciTech, 17, 148, 10.1208/s12249-015-0426-6

Goyanes, 2019, Direct powder extrusion 3D printing: Fabrication of drug products using a novel single-step process, Int. J. Pharm., 567, 118471, 10.1016/j.ijpharm.2019.118471

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

Smith, 2018, 3D printed capsules for quantitative regional absorption studies in the GI tract, Int. J. Pharm., 550, 418, 10.1016/j.ijpharm.2018.08.055

Huanbutta, 2019, Design and development of zero-order drug release gastroretentive floating tablets fabricated by 3D printing technology, J. Drug Deliv. Sci. Technol., 52, 831, 10.1016/j.jddst.2019.06.004

Kadry, 2018, Multi-purposable filaments of HPMC for 3D printing of medications with tailored drug release and timed-absorption, Int. J. Pharm., 544, 285, 10.1016/j.ijpharm.2018.04.010

Tagami, 2019, 3D printing of unique water-soluble polymer-based suppository shell for controlled drug release, Int. J. Pharm., 568, 118494, 10.1016/j.ijpharm.2019.118494

Breitkreutz, 2019, On-demand manufacturing of immediate release levetiracetam tablets using pressure-assisted microsyringe printing, Eur. J. Pharm. Biopharm., 134, 29, 10.1016/j.ejpb.2018.11.008

Khaled, 2018, 3D extrusion printing of high drug loading immediate release paracetamol tablets, Int. J. Pharm., 538, 223, 10.1016/j.ijpharm.2018.01.024

Li, 2018, Preparation and investigation of novel gastro-floating tablets with 3D extrusion-based printing, Int. J. Pharm., 535, 325, 10.1016/j.ijpharm.2017.10.037

Li, 2019, Flexibility of 3D Extruded Printing for a Novel Controlled-Release Puerarin Gastric Floating Tablet: Design of Internal Structure, AAPS PharmSciTech, 20, 1, 10.1208/s12249-019-1455-3

Siyawamwaya, 2019, 3D printed, controlled release, tritherapeutic tablet matrix for advanced anti-HIV-1 drug delivery, Eur. J. Pharm. Biopharm., 138, 99, 10.1016/j.ejpb.2018.04.007

Heidemann, 2019, Cold plasma treatment to improve the adhesion of cassava starch films onto PCL and PLA surface, Colloids Surfaces A, 580, 123739, 10.1016/j.colsurfa.2019.123739

Jawaid, M., Thariq, M., and Saba, N. (2019). 4-Dimensional stability of natural fiber-based and hybrid composites. Mechanical and Physical Testing of Biocomposites, Fibre-Reinforced Composites and Hybrid Composites, Woodhead Publishing.

Awaja, 2009, Adhesion of polymers, Prog. Polym. Sci., 34, 948, 10.1016/j.progpolymsci.2009.04.007

Messimer, S.L., Patterson, A.E., Muna, N., Deshpande, A.P., and Rocha Pereira, T. (2018). Characterization and Processing Behavior of Heated Aluminum-Polycarbonate Composite Build Plates for the FDM Additive Manufacturing Process. J. Manuf. Mater. Process., 2.

Santagata, 2016, Enhancement of interfacial adhesion between starch and grafted poly(ε-caprolactone), Carbohydr. Polym., 147, 16, 10.1016/j.carbpol.2016.03.070

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

Vakili, 2015, Hyperspectral imaging in quality control of inkjet printed personalised dosage forms, Int. J. Pharm., 483, 244, 10.1016/j.ijpharm.2014.12.034

Alomari, 2015, Personalised dosing: Printing a dose of one’s own medicine, Int. J. Pharm., 494, 568, 10.1016/j.ijpharm.2014.12.006

Cheah, 2002, Characterization of microfeatures in selective laser sintered drug delivery devices, Proc. Inst. Mech. Eng. Part H J. Eng. Med., 216, 369, 10.1243/095441102321032166

Amza, C., Zapciu, A., and Popescu, D. (2017). Paste Extruder—Hardware Add-On for Desktop 3D Printers. Technologies, 5.

Neches, 2016, On the intrinsic sterility of 3D printing, PeerJ., 4, e2661, 10.7717/peerj.2661

Campbell, 2017, Pharma to table: 3-D printing and the regulatory future of home remedies, Conn. L. Rev. CONNtemplations, 49, 1

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

Cheng, 1999, Studies of Hydroxypropyl Methylcellulose Donut-Shaped Tablets, Drug Dev. Ind. Pharm., 25, 1067, 10.1081/DDC-100102271

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

Food, U., and Administration, D. (2019, December 15). Facts about the Current Good Manufacturing Practices (CGMPs), Available online: https://www.fda.gov/drugs/pharmaceutical-quality-resources/facts-about-current-good-manufacturing-practices-cgmps.

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

Sanderson, 2015, 3D printing: The future of manufacturing medicine, Pharm. J., 294, 598

FDA (2019, December 16). Are You Taking Medication as Prescribed?, Available online: https://www.fda.gov/consumers/consumer-updates/are-you-taking-medication-prescribed.

Florence, 2011, Personalised medicines: More tailored drugs, more tailored delivery, Int. J. Pharm., 415, 29, 10.1016/j.ijpharm.2011.04.047

Schiele, 2013, Difficulties swallowing solid oral dosage forms in a general practice population: Prevalence, causes, and relationship to dosage forms, Eur. J. Clinical Pharmacol., 69, 937, 10.1007/s00228-012-1417-0

Spence, 2008, Polypill: For Pollyanna, Int. J. Stroke, 3, 92, 10.1111/j.1747-4949.2008.00169.x

Pharmaceuticals, C. (2019, December 16). About PolycapTM. Available online: http://www.polycap.org/.

Urquhart, 2009, The indian polycap study (TIPS), Lancet, 374, 781, 10.1016/S0140-6736(09)61586-5

Wu, 2009, A programmed release multi-drug implant fabricated by three-dimensional printing technology for bone tuberculosis therapy, Biomed. Mater., 4, 065005, 10.1088/1748-6041/4/6/065005

Acosta-Vélez, G., Linsley, C., Zhu, T., Wu, W., and Wu, B. (2018). Photocurable Bioinks for the 3D Pharming of Combination Therapies. Polymers, 10.

Haring, 2018, Programming of multicomponent temporal release profiles in 3D printed polypills via core–shell, multilayer, and gradient concentration profiles, Adv. Healthc. Mater., 7, 1800213, 10.1002/adhm.201800213

Genina, 2019, Perceptions, preferences and acceptability of patient designed 3D printed medicine by polypharmacy patients: A pilot study, Int. J. Clin. Pharm., 41, 1290, 10.1007/s11096-019-00892-6

Robles-Martinez, P., Xu, X., Trenfield, S.J., Awad, A., Goyanes, A., Telford, R., Basit, A.W., and Gaisford, S. (2019). 3D Printing of a Multi-Layered Polypill Containing Six Drugs Using a Novel Stereolithographic Method. Pharmaceutics, 11.

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