Novel Excipients and Materials Used in FDM 3D Printing of Pharmaceutical Dosage Forms

Ming Lu

Sun Yat-sen University, School of Pharmaceutical Sciences, Department of Pharmaceutics, No. 132, Waihuan Dong Road, Guangzhou, 510006, China

Search for more papers by this author

Ming Lu,

Ming Lu

Sun Yat-sen University, School of Pharmaceutical Sciences, Department of Pharmaceutics, No. 132, Waihuan Dong Road, Guangzhou, 510006, China

Search for more papers by this author

Book Editor(s):Mohammed Maniruzzaman,

Mohammed Maniruzzaman

School of Life Sciences, University of Sussex, Brighton, UK, BN1 9QG

Search for more papers by this author

First published: 14 December 2018

https://doi.org/10.1002/9783527813704.ch9

Citations: 5

Summary

This chapter highlights the polymeric materials and excipients used in pharmaceutical fused deposition modeling (FDM) 3D printing. Polylactic acid (PA) and acrylonitrile butadiene styrene (ABS) are the most widely used materials in a 3D printing technique. Generally, PLA is an ideal polymer material for the fabrication of medical devices with sustained drug release. Polyvinyl alcohol (PVA) is manufactured by the polymerization of vinyl acetate (VA) followed by partial or full hydrolysis. Ethylene vinyl acetate (EVA), a copolymer of ethylene and VA, is one of the most extensively used nondegradable polymers in pharmaceutical implant because of its excellent flexibility and good biocompatability. Hydroxypropyl methylcellulose acetate succinate (HPMCAS) is a polymer candidate to fabricated enteric tablets by FDM 3D printing technology. Polymethacrylates are a group of pH-sensitive polymers. Eudragit RL and Eudragit RS are insoluble but permeable in gastrointestinal tract. Eudragit E could be used in FDM 3D printing as an immediate release matrix former.

References

Maroni, A., Melocchi, A., Parietti, F. et al. (2017). 3D printed multi-compartment capsular devices for two-pulse oral drug delivery. Journal of Controlled Release 268: 10–18.
10.1016/j.jconrel.2017.10.008
CAS PubMed Web of Science® Google Scholar
Long, J., Gholizadeh, H., Lu, J. et al. (2017). Application of fused deposition modelling (FDM) method of 3D printing in drug delivery. Current Pharmaceutical Design 23 (3): 433–439.
10.2174/1381612822666161026162707
CAS PubMed Web of Science® Google Scholar
Norman, J., Madurawe, R.D., Moore, C.M.V. et al. (2017). A new chapter in pharmaceutical manufacturing: 3D-printed drug products. Advanced Drug Delivery Reviews 108: 39–50.
10.1016/j.addr.2016.03.001
CAS PubMed Web of Science® Google Scholar
Goyanes, A., Fernández-Ferreiro, A., Majeed, A. et al. (2018). PET/CT imaging of 3D printed devices in the gastrointestinal tract of rodents. International Journal of Pharmaceutics 536 (1): 158–164.
10.1016/j.ijpharm.2017.11.055
CAS PubMed Web of Science® Google Scholar
Li, Q., Guan, X., Cui, M. et al. (2018). Preparation and investigation of novel gastro-floating tablets with 3D extrusion-based printing. International Journal of Pharmaceutics 535 (1–2): 325–332.
Google Scholar
Yang, Y., Wang, H., Li, H. et al. (2018). 3D printed tablets with internal scaffold structure using ethyl cellulose to achieve sustained ibuprofen release. European Journal of Pharmaceutical Sciences 115: 11–18.
10.1016/j.ejps.2018.01.005
CAS PubMed Web of Science® Google Scholar
Genina, N., Hollander, J., Jukarainen, H. et al. (2016). Ethylene vinyl acetate (EVA) as a new drug carrier for 3D printed medical drug delivery devices. European Journal of Pharmaceutical Sciences 90: 53–63.
10.1016/j.ejps.2015.11.005
CAS PubMed Web of Science® Google Scholar
Melocchi, A., Parietti, F., Loreti, G. et al. (2015). 3D printing by fused deposition modeling (FDM) of a swellable/erodible capsular device for oral pulsatile release of drugs. Journal of Drug Delivery Science and Technology 30 (Part B): 360–367.
10.1016/j.jddst.2015.07.016
CAS Web of Science® Google Scholar
Alhijjaj, M., Belton, P., and Qi, S. (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. European Journal of Pharmaceutics and Biopharmaceutics 108: 111–125.
10.1016/j.ejpb.2016.08.016
CAS PubMed Web of Science® Google Scholar
Goyanes, A., Det-Amornrat, U., Wang, J. et al. (2016). 3D scanning and 3D printing as innovative technologies for fabricating personalized topical drug delivery systems. Journal of Controlled Release 234: 41–48.
10.1016/j.jconrel.2016.05.034
CAS PubMed Web of Science® Google Scholar
Sadia, M., Sosnicka, A., Arafat, B. et al. (2016). Adaptation of pharmaceutical excipients to FDM 3D printing for the fabrication of patient-tailored immediate release tablets. International Journal of Pharmaceutics 513 (1-2): 659–668.
10.1016/j.ijpharm.2016.09.050
CAS PubMed Web of Science® Google Scholar
Zhang, J., Feng, X., Patil, H. et al. (2017). Coupling 3D printing with hot-melt extrusion to produce controlled-release tablets. International Journal of Pharmaceutics 519 (1–2): 186–197.
10.1016/j.ijpharm.2016.12.049
CAS PubMed Web of Science® Google Scholar
Pietrzak, K., Isreb, A., and Alhnan, M.A. (2015). A flexible-dose dispenser for immediate and extended release 3D printed tablets. European Journal of Pharmaceutics and Biopharmaceutics 96: 380–387.
10.1016/j.ejpb.2015.07.027
CAS PubMed Web of Science® Google Scholar
Water, J.J., Bohr, A., Boetker, J. et al. (2015). Three-dimensional printing of drug-eluting implants: preparation of an antimicrobial polylactide feedstock material. Journal of Pharmaceutical Sciences 104 (3): 1099–1107.
10.1002/jps.24305
CAS PubMed Web of Science® Google Scholar
DiNunzio, J.C., Zhang, F., Martin, C., and McGinity, J.W. (2012). Melt extrusion. In: Formulating Poorly Water Soluble Drugs, 1e (ed. R.O. Williams, A.B. Watts and D.A. Miller), 311–362. New York: Springer.
10.1007/978-1-4614-1144-4_9
Web of Science® Google Scholar
Wang, B., Wang, D., Zhao, S. et al. (2017). Evaluate the ability of PVP to inhibit crystallization of amorphous solid dispersions by density functional theory and experimental verify. European Journal of Pharmaceutical Sciences 96: 45–52.
10.1016/j.ejps.2016.08.046
Google Scholar
Kojo, Y., Matsunaga, S., Suzuki, H. et al. (2017). Improved oral absorption profile of itraconazole in hypochlorhydria by self-micellizing solid dispersion approach. European Journal of Pharmaceutical Sciences 97: 55–61.
10.1016/j.ejps.2016.10.032
Google Scholar
Yewale, C., Tandel, H., and Misra, A. (2014). Application of polymers in transdermal drug delivery. In: Applications of Polymers in Drug Delivery (ed. A. Misra and A. Shahiwala). Shawbury, UK: Smithers Rapra Technology Ltd.
Google Scholar
Melocchi, A., Parietti, F., Maroni, A. et al. (2016). Hot-melt extruded filaments based on pharmaceutical grade polymers for 3D printing by fused deposition modeling. International Journal of Pharmaceutics 509 (1–2): 255–263.
10.1016/j.ijpharm.2016.05.036
CAS PubMed Web of Science® Google Scholar
Goyanes, A., Buanz, A.B.M., Hatton, G.B. et al. (2015). 3D printing of modified-release aminosalicylate (4-ASA and 5-ASA) tablets. European Journal of Pharmaceutics and Biopharmaceutics 89: 157–162.
10.1016/j.ejpb.2014.12.003
CAS PubMed Web of Science® Google Scholar
Williams, C.K. and Hillmyer, M.A. (2008). Polymers from renewable resources: a perspective for a special issue of polymer reviews. Polymer Reviews 48 (1): 1–10.
10.1080/15583720701834133
CAS Web of Science® Google Scholar
Sandler, N., Salmela, I., Fallarero, A. et al. (2014). Towards fabrication of 3D printed medical devices to prevent biofilm formation. International Journal of Pharmaceutics 459 (1–2): 62–64.
10.1016/j.ijpharm.2013.11.001
CAS PubMed Web of Science® Google Scholar
Boetker, J., Water, J.J., Aho, J. et al. (2016). Modifying release characteristics from 3D printed drug-eluting products. European Journal of Pharmaceutical Sciences 90: 47–52.
10.1016/j.ejps.2016.03.013
CAS PubMed Web of Science® Google Scholar
Chen, D.R., Chen, H.L., Bei, J.Z., and Wang, S.G. (2000). Morphology and biodegradation of microspheres of polyester-polyether block copolymer based on polycaprolactone/polylactide/poly(ethylene oxide). Polymer International 49 (3): 269–276.
10.1002/(SICI)1097-0126(200003)49:3<269::AID-PI358>3.0.CO;2-Z
CAS Web of Science® Google Scholar
Sivalingam, G., Karthik, R., and Madras, G. (2004). Blends of poly(epsilon-caprolactone) and poly(vinyl acetate): mechanical properties and thermal degradation. Polymer Degradation and Stability 84 (2): 345–351.
Google Scholar
Holländer, J., Genina, N., Jukarainen, H. et al. (2016). Three-dimensional printed PCL-based implantable prototypes of medical devices for controlled drug delivery. Journal of Pharmaceutical Sciences 105 (9): 2665–2676.
10.1016/j.xphs.2015.12.012
CAS PubMed Web of Science® Google Scholar
Park, J.C., Ito, T., Kim, K.O. et al. (2010). Electrospun poly(vinyl alcohol) nanofibers: effects of degree of hydrolysis and enhanced water stability. Polymer Journal 42 (3): 273–276.
10.1038/pj.2009.340
CAS Web of Science® Google Scholar
Goyanes, A., Buanz, A.B.M., Basit, A.W., and Gaisford, S. (2014). Fused-filament 3D printing (3DP) for fabrication of tablets. International Journal of Pharmaceutics 476 (1–2): 88–92.
10.1016/j.ijpharm.2014.09.044
CAS PubMed Web of Science® Google Scholar
Skowyra, J., Pietrzak, K., and Alhnan, M.A. (2015). Fabrication of extended-release patient-tailored prednisolone tablets via fused deposition modelling (FDM) 3D printing. European Journal of Pharmaceutical Sciences 68: 11–17.
10.1016/j.ejps.2014.11.009
CAS PubMed Web of Science® Google Scholar
Goyanes, A., Chang, H., Sedough, D. et al. (2015). Fabrication of controlled-release budesonide tablets via desktop (FDM) 3D printing. International Journal of Pharmaceutis 496 (2): 414–420.
Google Scholar
Goyanes, A., Martinez, P.R., Buanz, A. et al. (2015). Effect of geometry on drug release from 3D printed tablets. International Journal of Pharmaceutics 494 (2): 657–663.
10.1016/j.ijpharm.2015.04.069
CAS PubMed Web of Science® Google Scholar
Goyanes, A., Wang, J., Buanz, A. et al. (2015). 3D printing of medicines: engineering novel oral devices with unique design and drug release characteristics. Molecular Pharmaceutics 12 (11): 4077–4084.
10.1021/acs.molpharmaceut.5b00510
CAS PubMed Web of Science® Google Scholar
Goyanes, A., Kobayashi, M., Martinez-Pacheco, R. et al. (2016). Fused-filament 3D printing of drug products: Microstructure analysis and drug release characteristics of PVA-based caplets. International Journal of Pharmaceutics 514 (1): 290–295.
10.1016/j.ijpharm.2016.06.021
CAS PubMed Web of Science® Google Scholar
Li, Q., Wen, H., Ji, D. et al. (2017). Preparation and investigation of controlled-release glipizide novel oral device with three-dimensional printing. International Journal of Pharmaceutics 525 (1): 5–11.
Google Scholar
K. Kolter, M. Karl, and A. Gryczke (eds.) (2012). Hot-melt Extrusion with BASF Pharma Polymers: Extrusion Compendium. Germany: Ludwigshafen.
Google Scholar
Knopp, M.M., Nguyen, J.H., Becker, C. et al. (2016). Influence of polymer molecular weight on in vitro dissolution behavior and in vivo performance of celecoxib:PVP amorphous solid dispersions. European Journal of Pharmaceutics and Biopharmaceutics 101: 145–151.
10.1016/j.ejpb.2016.02.007
CAS Web of Science® Google Scholar
Okwuosa, T.C., Stefaniak, D., Arafat, B. et al. (2016). A lower temperature FDM 3D printing for the manufacture of patient-specific immediate release tablets. Pharmaceutical Research 33 (11): 2704–2712.
10.1007/s11095-016-1995-0
CAS PubMed Web of Science® Google Scholar
Meena, A., Parikh, T., Gupta, S.S., and Serajuddin, A.T.M. (2014). Investigation of thermal and viscoelastic properties of polymers relevant to hot melt extrusion – II: cellulosic polymers. Journal of Excipients and Food Chemicals 5 (1): 46–55.
Google Scholar
Repka, M.A., Gerding, T.G., Repka, S.L., and McGinity, J.W. (1999). Influence of plasticizers and drugs on the physical-mechanical properties of hydroxypropylcellulose films prepared by hot melt extrusion. Drug Development and Industrial Pharmacy 25 (5): 625–633.
10.1081/DDC-100102218
CAS PubMed Web of Science® Google Scholar
Repka, M.A. and McGinity, J.W. (2001). Bioadhesive properties of hydroxypropylcellulose topical films produced by hot-melt extrusion. Journal of Controlled Release 70 (3): 341–351.
10.1016/S0168-3659(00)00365-5
CAS PubMed Web of Science® Google Scholar
LaFountaine, J.S., McGinity, J.W., and Williams, R.O. (2016). Challenges and strategies in thermal processing of amorphous solid dispersions: a review. AAPS PharmSciTech 17 (1): 43–55.
10.1208/s12249-015-0393-y
CAS PubMed Web of Science® Google Scholar
Jermain, S.V., Brough, C., and Williams, R.O. (2018). Amorphous solid dispersions and nanocrystal technologies for poorly water-soluble drug delivery – an update. International Journal of Pharmaceutics 535 (102): 379–392.
Google Scholar
Zhang, J., Yang, W., Vo, A.Q. et al. (2017). Hydroxypropyl methylcellulose-based controlled release dosage by melt extrusion and 3D printing: Structure and drug release correlation. Carbohydrate Polymers 177 (1): 49–57.
Google Scholar
AquaSolve™ hydroxypropylmethylcellulose acetate succinate – Physical and chemical properties handbook. http://www.ashland.com/file_source/Ashland/Industries/Pharmaceutical/Links/PC-12624.6_AquaSolve_HPMCAS_Physical_Chemical_Properties.pdf (accessed 01 January 2018).
Google Scholar
Goyanes, A., Fina, F., Martorana, A. et al. (2017). Development of modified release 3D printed tablets (printlets) with pharmaceutical excipients using additive manufacturing. International Journal of Pharmaceutics 527 (1–2): 21–30.
10.1016/j.ijpharm.2017.05.021
CAS PubMed Web of Science® Google Scholar
Nollenberger, K. and Albers, J. (2012). Applications of poly(meth)acrylate polymers in melt extrusion. In: Hot-melt Extrusion: Pharmaceutical Applications (ed. D. Douroumis). Chichester, UK: Wiley.
10.1002/9780470711415.ch6
Google Scholar
Okwuosa, T.C., Pereira, B.C., Arafat, B. et al. (2017). Fabricating a shell–core delayed release tablet using dual FDM 3D printing for patient-centred therapy. Pharmaceutical Research 34 (2): 427–437.
10.1007/s11095-016-2073-3
Google Scholar
Khorasani, M., Edinger, M., Raijada, D. et al. (2016). Near-infrared chemical imaging (NIR-CI) of 3D printed pharmaceuticals. International Journal of Pharmaceutics 515 (1–2): 324–330.
CAS PubMed Web of Science® Google Scholar
Solanki, N.G., Tahsin, M., Shah, A.V., and Serajuddin, A.T.M. (2018). Formulation of 3D printed tablet for rapid drug release by fused deposition modeling: screening polymers for drug release, drug-polymer miscibility and printability. Journal of Pharmaceutical Sciences 107 (1): 390–401.
10.1016/j.xphs.2017.10.021
CAS PubMed Web of Science® Google Scholar
Sadia, M., Arafat, B., Ahmed, W. et al. (2018). Channelled tablets: an innovative approach to accelerating drug release from 3D printed tablets. Journal of Controlled Release 269: 355–363.
10.1016/j.jconrel.2017.11.022
CAS PubMed Web of Science® Google Scholar
Riva, A., Zanetti, M., Braglia, M. et al. (2002). Thermal degradation and rheological behaviour of EVA/montmorillonite nanocomposites. Polymer Degradation and Stability 77 (2): 299–304.
10.1016/S0141-3910(02)00065-4
Web of Science® Google Scholar
Hall, M. and Read, M. (2012). Hot-melt extrusion of ethylcellulose, hypromellose and polyethylene oxide. In: Hot-melt Extrusion: Pharmaceutical Applications (ed. D. Douroumis). Chichester, UK: Wiley.
10.1002/9780470711415.ch7
Google Scholar

Citing Literature

3D and 4D Printing in Biomedical Applications: Process Engineering and Additive Manufacturing