Abstract
Commercial stereolithography (SLA) 3D printing has been around for over three decades. However, only recently the technology has been employed in pharmaceuticals to 3D print pills and devices for drug delivery, aided in part by the miniaturization of this technology. Compared to other 3D printing technologies based on powder or filament-based feedstock, SLA offers superior surface finish, accuracy, and material versatility. This chapter covers the major advancements in SLA 3D printing of pharmaceuticals and provides insight into the origin of SLA 3D printing and the current subcategories within this technology, the important governing process parameters, various applications in pharmaceuticals from peer-reviewed literature, and challenges that must be addressed to bring the technology closer to the clinic. Using SLA, rigid pills loaded with drugs such as paracetamol, caffeine, naproxen, chloramphenicol, prednisolone, aspirin, and berberine have been successfully 3D printed. In addition, soft devices for drug release have also been 3D printed. However, unexpected reactions have been reported in the literature which emphasize the cautionary aspect of 3D printing pharmaceuticals using SLA and the need for further meticulous research. Additionally, the regulatory hurdles including a general lack of quality control processes need to be addressed to bring this technology into the clinic. The throughput of SLA 3D printing for pharmaceuticals, like other 3D printing technologies, is substantially lower compared to conventional industrial fabrication processes. Further, post-processing steps such as support structure removal and post-curing are needed to achieve the desired end-use characteristics. However, a novel technique of volumetric 3D printing of pharmaceuticals holds promise to address some of these limitations, but the technology is still in the nascent stage and technical challenges such as dimensional accuracy and material compatibility still need to be addressed. SLA 3D printing of pharmaceuticals is a new and active area of research with potential to impact clinical practice in the future as critical roadblocks are addressed.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Alexander AE, Wake N, Chepelev L, Brantner P, Ryan J, Wang KC (2021) A guideline for 3D printing terminology in biomedical research utilizing ISO/ASTM standards. 3D Print Med 7:4–9. https://doi.org/10.1186/s41205-021-00098-5
Awad A, Trenfield SJ, Goyanes A, Gaisford S, Basit AW (2018) Reshaping drug development using 3D printing. Drug Discov Today 23:1547–1555. https://doi.org/10.1016/j.drudis.2018.05.025
Bloomquist CJ, Mecham MB, Paradzinsky MD, Janusziewicz R, Warner SB, Luft JC, Mecham SJ, Wang AZ, DeSimone JM (2018) Controlling release from 3D printed medical devices using CLIP and drug-loaded liquid resins. J Control Release 278:9–23. https://doi.org/10.1016/j.jconrel.2018.03.026
Brambilla CRM, Okafor-muo OL, Hassanin H, Elshaer A (2021) 3dp printing of oral solid formulations: a systematic review. Pharmaceutics 13:1–25. https://doi.org/10.3390/pharmaceutics13030358
Campbell I, Bourell D, Gibson I (2012) Additive manufacturing: rapid prototyping comes of age. Rapid Prototyp J 18:255–258. https://doi.org/10.1108/13552541211231563
Caudill CL, Perry JL, Tian S, Luft JC, DeSimone JM (2018) Spatially controlled coating of continuous liquid Interface production microneedles for transdermal protein delivery. J Control Release 284:122–132. https://doi.org/10.1016/j.jconrel.2018.05.042
CDER (2018) Small Business and Industry Assistance (SBIA), PDUFA VI : a time for change
Curti C, Kirby DJ, Russell CA (2021) Stereolithography apparatus evolution: enhancing throughput and efficiency of pharmaceutical formulation development. Pharmaceutics 13. https://doi.org/10.3390/pharmaceutics13050616
Deshmane S, Kendre P, Mahajan H, Jain S (2021) Stereolithography 3D printing technology in pharmaceuticals: a review. Drug Dev Ind Pharm 0:1–11. https://doi.org/10.1080/03639045.2021.1994990
Di Prima M, Coburn J, Hwang D, Kelly J, Khairuzzaman A, Ricles L (2016) Additively manufactured medical products—the FDA perspective. 3D Print Med 2:4–9. https://doi.org/10.1186/s41205-016-0005-9
Economidou SN, Pere CPP, Reid A, Uddin MJ, Windmill JFC, Lamprou DA, Douroumis D (2019) 3D printed microneedle patches using stereolithography (SLA)for intradermal insulin delivery. Mater Sci Eng C 102:743–755. https://doi.org/10.1016/j.msec.2019.04.063
Elkasabgy NA, Mahmoud AA, Maged A (2020) 3D printing: an appealing route for customized drug delivery systems. Int J Pharm 588:119732. https://doi.org/10.1016/j.ijpharm.2020.119732
Fernández-García R, Prada M, Bolás-Fernández F, Ballesteros MP, Serrano DR (2020) Oral fixed-dose combination pharmaceutical products: industrial manufacturing versus personalized 3D printing. Pharm Res 37:132. https://doi.org/10.1007/s11095-020-02847-3
Healy AV, Fuenmayor E, Doran P, Geever LM, Higginbotham CL, Lyons JG (2019) Additive manufacturing of personalized pharmaceutical dosage forms via stereolithography. Pharmaceutics 11:13–15. https://doi.org/10.3390/pharmaceutics11120645
Huang J, Qin Q, Wang J (2020) A review of stereolithography: processes and systems. PRO 8. https://doi.org/10.3390/PR8091138
Hull CW (1986) Apparatus for production of three-dimensional objects by Stereolithography
Jamróz W, Szafraniec J, Kurek M, Jachowicz R (2018) 3D printing in pharmaceutical and medical applications. Pharm Res 35:1–22. https://doi.org/10.1007/s11095-018-2454-x
Januskaite P, Xu X, Ranmal SR, Gaisford S, Basit AW, Tuleu C, Goyanes A (2020) I spy with my little eye: a paediatric visual preferences survey of 3d printed tablets. Pharmaceutics 12:1–16. https://doi.org/10.3390/pharmaceutics12111100
Johnson AR, Caudill CL, Tumbleston JR, Bloomquist CJ, Moga KA, Ermoshkin A, Shirvanyants D, Mecham SJ, Luft JC, De Simone JM (2016) Single-step fabrication of computationally designed microneedles by continuous liquid interface production. PLoS One 11:1–17. https://doi.org/10.1371/journal.pone.0162518
Kadry H, Wadnap S, Xu C, Ahsan F (2019) Digital light processing (DLP)3D-printing technology and photoreactive polymers in fabrication of modified-release tablets. Eur J Pharm Sci 135:60–67. https://doi.org/10.1016/j.ejps.2019.05.008
Karakurt I, Aydoğdu A, Çıkrıkcı S, Orozco J, Lin L (2020) Stereolithography (SLA) 3D printing of ascorbic acid loaded hydrogels: a controlled release study. Int J Pharm 584:1–9. https://doi.org/10.1016/j.ijpharm.2020.119428
Konasch J, Riess A, Mau R, Teske M, Rekowska N, Eickner T, Grabow N, Seitz H (2019) A novel hybrid additive manufacturing process for drug delivery systems with locally incorporated drug depots. Pharmaceutics 11:1–14. https://doi.org/10.3390/pharmaceutics11120661
Krkobabić M, Medarević D, Cvijić S, Grujić B, Ibrić S (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. https://doi.org/10.1016/j.ijpharm.2019.118790
Lim SH, Ng JY, Kang L (2017) Three-dimensional printing of a microneedle array on personalized curved surfaces for dual-pronged treatment of trigger finger. Biofabrication 9. https://doi.org/10.1088/1758-5090/9/1/015010
Lim SH, Kathuria H, Bin Amir MH, Zhang X, Duong HTT, Ho PCL, Kang L (2021) High resolution photopolymer for 3D printing of personalised microneedle for transdermal delivery of anti-wrinkle small peptide. J Control Release 329:907–918. https://doi.org/10.1016/j.jconrel.2020.10.021
Lu Y, Mantha SN, Crowder DC, Chinchilla S, Shah KN, Yun YH, Wicker RB, Choi JW (2015) Microstereolithography and characterization of poly(propylene fumarate)-based drug-loaded microneedle arrays. Biofabrication 7. https://doi.org/10.1088/1758-5090/7/4/045001
Madzarevic M, Medarevic D, Vulovic A, Sustersic T, Djuris J, Filipovic N, Ibric S (2019) Optimization and prediction of ibuprofen release from 3D DLP printlets using artificial neural networks. Pharmaceutics 11. https://doi.org/10.3390/pharmaceutics11100544
Martinez PR, Goyanes A, Basit AW, Gaisford S (2017) Fabrication of drug-loaded hydrogels with stereolithographic 3D printing. Int J Pharm 532:313–317. https://doi.org/10.1016/j.ijpharm.2017.09.003
Martinez PR, Basit AW, Gaisford S (2018a) The history, developments and opportunities of stereolithography. 3D Print Pharm:55–79. https://doi.org/10.1007/978-3-319-90755-0_4
Martinez PR, Goyanes A, Basit AW, Gaisford S (2018b) Influence of geometry on the drug release profiles of stereolithographic (SLA) 3D-printed tablets. AAPS PharmSciTech 19:3355–3361. https://doi.org/10.1208/s12249-018-1075-3
Mathew E, Pitzanti G, Larrañeta E, Lamprou DA (2020) Three-dimensional printing of pharmaceuticals and drug delivery devices. Pharmaceutics 12:1–9. https://doi.org/10.3390/pharmaceutics12030266
Mitsouras D, Liacouras P, Imanzadeh A, Giannopoulos AA, Cai T, Kumamaru KK, George E, Wake N, Caterson EJ, Pomahac B, Ho VB, Grant GT, Rybicki FJ (2015) Medical 3D printing for the radiologist. Radiographics 35:1965–1988. https://doi.org/10.1148/rg.2015140320
Ożóg P, Elsayed H, Grigolato L, Savio G, Kraxner J, Galusek D, Bernardo E (2022) Engineering of silicone-based blends for the masked stereolithography of biosilicate/carbon composite scaffolds. J Eur Ceram Soc 42:6192–6198. https://doi.org/10.1016/j.jeurceramsoc.2022.06.057
Pagac M, Hajnys J, Ma Q, Jancar L, Jansa J, Stefek P, Mesicek J (2021) A review of vat photopolymerization technology: materials, applications, challenges, and future trends of 3D printing. Polymers 13, 4:598. https://doi.org/10.3390/polym13040598
Pariskar A, Sharma PK, Murty US, Banerjee S (2022) Effect of tartrazine as photoabsorber for improved printing resolution of 3D printed “ghost tablets”: non-erodible inert matrices. J Pharm Sci 000:1020. https://doi.org/10.1016/j.xphs.2022.11.014
Patel PT (2018) Additive manufacturing process investigation for the fabrication of composite scaffolds for soft tissue application. http://forschungsunion.de/pdf/industrie_4_0_umsetzungsempfehlungen.pdf%0Ahttps://www.dfki.de/fileadmin/user_upload/import/9744_171012-KI-Gipfelpapier-online.pdf%0Ahttps://www.bitkom.org/sites/default/files/pdf/Presse/Anhaenge-an-PIs/2018/180607-Bitkom
Patel P, Saini T, Welch T, Ravi P, Shiakolas P (2018) Additive manufacturing of heterogeneous bio-Resorbable constructs for soft tissue applications. In: Proc Mater Sci Technol Conf, pp 1496–1503. https://doi.org/10.7449/2018mst/2018/mst_2018_1496_1503
Patel P, Rane R, Mrinal M, Ganesan V, Taylor R, Jain A (2022) Characterization of the effect of in-process annealing using a novel print head assembly on the ultimate tensile strength & toughness of fused filament fabrication (FFF) parts. Virtual Phys Prototyp 17:989–1005. https://doi.org/10.1080/17452759.2022.2095288
Pere CPP, Economidou SN, Lall G, Ziraud C, Boateng JS, Alexander BD, Lamprou DA, Douroumis D (2018) 3D printed microneedles for insulin skin delivery. Int J Pharm 544:425–432. https://doi.org/10.1016/j.ijpharm.2018.03.031
Ravi P (2020) Understanding the relationship between slicing and measured fill density in material extrusion 3D printing towards precision porosity constructs for biomedical and pharmaceutical applications. 3D Print Med 6:1–10. https://doi.org/10.1186/s41205-020-00063-8
Ravi P, Shiakolas PS (2021) Effects of slicing parameters on measured fill density for 3D printing of precision cylindrical constructs using Slic3r. SN Appl Sci 3. https://doi.org/10.1007/s42452-021-04398-7
Ravi P, Shiakolas PS, Welch TR (2017) Poly- l -lactic acid: pellets to fiber to fused filament fabricated scaffolds, and scaffold weight loss study. Addit Manuf 16:167–176. https://doi.org/10.1016/j.addma.2017.06.002
Ravi P, Wright J, Shiakolas PS, Welch TR (2019) Three-dimensional printing of poly(glycerol sebacate fumarate) gadodiamide-poly(ethylene glycol) diacrylate structures and characterization of mechanical properties for soft tissue applications. J Biomed Mater Res Part B Appl Biomater 107:664–671. https://doi.org/10.1002/jbm.b.34159
Ravi P, Chepelev L, Lawera N, Haque KMA, Chen VCP, Ali A, Rybicki FJ (2021a) A systematic evaluation of medical 3D printing accuracy of multi-pathological anatomical models for surgical planning manufactured in elastic and rigid material using desktop inverted vat photopolymerization. Med Phys 48:3223–3233. https://doi.org/10.1002/mp.14850
Ravi P, Antoline S, Rybicki FJ (2021b) 3D printing of open-source respirators (including N95 respirators), surgical masks, and community mask designs to address COVID-19 shortages, in: 3D Print Med Its role COVID-19 pandemic, Springer, pp 91–106. doi:https://doi.org/10.1007/978-3-030-61993-0
Ravi P, Chepelev LL, Stichweh GV, Jones BS, Rybicki FJ (2022a) Medical 3D printing dimensional accuracy for multi-pathological anatomical models 3D printed using material extrusion. J Digit Imaging 35:613–622. https://doi.org/10.1007/s10278-022-00614-x
Ravi P, Burch MB, Farahani S, Chepelev LL, Yang D, Ali A, Joyce JR, Lawera N, Stringer J, Morris JM, Ballard DH, Wang KC, Mahoney MC, Kondor S, Rybicki FJ, Rabinowitz YA, Shapiro SB, McCormick B, Costea AI, Byrd S, Panza A, Danesi TH, Giglia JS, Chadalavada S, Krishnan DG, Cervenka BP, Phero JA, McLaurin WS, Sidana A, Utz CJ, Grawe B (2022b) Utility and costs during the initial year of 3D printing in an academic hospital. J Am Coll Radiol 20:193. https://doi.org/10.1016/j.jacr.2022.07.001
Robles-Martinez P, Xu X, Trenfield SJ, Awad A, Goyanes A, Telford R, Basit AW, Gaisford S (2019) 3D printing of a multi-layered polypill containing six drugs using a novel stereolithographic method. Pharmaceutics 11. https://doi.org/10.3390/pharmaceutics11060274
Rodríguez-Pombo L, Xu X, Seijo-Rabina A, Ong JJ, Alvarez-Lorenzo C, Rial C, Nieto D, Gaisford S, Basit AW, Goyanes A (2022) Volumetric 3D printing for rapid production of medicines. Addit Manuf 52:102673. https://doi.org/10.1016/j.addma.2022.102673
Seoane-Viaño I, Trenfield SJ, Basit AW, Goyanes A (2021) Translating 3D printed pharmaceuticals: from hype to real-world clinical applications. Adv Drug Deliv Rev 174:553–575. https://doi.org/10.1016/j.addr.2021.05.003
Serbin J, Ovsianikov A, Chichkov B (2004) Fabrication of woodpile structures by two-photon polymerization and investigation of their optical properties. Opt Express 12:5221. https://doi.org/10.1364/opex.12.005221
Sharma PK, Choudhury D, Yadav V, Murty USN, Banerjee S (2022) 3D printing of nanocomposite pills through desktop vat photopolymerization (stereolithography) for drug delivery reasons. 3D Print Med 8:1–10. https://doi.org/10.1186/s41205-022-00130-2
Stanojević G, Medarević D, Adamov I, Pešić N, Kovačević J, Ibrić S (2020) Tailoring atomoxetine release rate from DLP 3D-printed tablets using artificial neural networks: influence of tablet thickness and drug loading. Molecules 26. https://doi.org/10.3390/molecules26010111
Tan EL, Ho PCL (2019) Stereolithographic 3D printing (SLA 3DP) of pharmaceutical tablets. Trans Addit Manuf Meets Med 1:2–3. https://doi.org/10.18416/AMMM.2019.1909S03P13
Tino R, Moore R, Antoline S, Ravi P, Wake N, Ionita CN, Morris JM, Decker SJ, Sheikh A, Rybicki FJ, Chepelev LL (2020) COVID-19 and the role of 3D printing in medicine. 3D Print Med 6:1–8. https://doi.org/10.1186/s41205-020-00064-7
Trenfield SJ, Awad A, Goyanes A, Gaisford S, Basit AW (2018) 3D printing pharmaceuticals: drug development to frontline care. Trends Pharmacol Sci 39:440–451. https://doi.org/10.1016/j.tips.2018.02.006
Trenfield SJ, Awad A, Madla CM, Hatton GB, Firth J, Goyanes A, Gaisford S, Basit AW (2019) Shaping the future: recent advances of 3D printing in drug delivery and healthcare. Expert Opin Drug Deliv 16:1081–1094. https://doi.org/10.1080/17425247.2019.1660318
Tumbleston JR, Shirvanyants D, Ermoshkin N, Janusziewicz R, Johnson AR, Kelly D, Chen K, Pinschmidt R, Rolland JP, Ermoshkin A, Samulski ET, Desimone JM (2015) Continuous liquid interface production of 3D objects. Science (80-.) 347:1349–1352. https://doi.org/10.1126/science.aaa2397
Uddin MJ, Scoutaris N, Economidou SN, Giraud C, Chowdhry BZ, Donnelly RF, Douroumis D (2020) 3D printed microneedles for anticancer therapy of skin tumours. Mater Sci Eng C 107:110248. https://doi.org/10.1016/j.msec.2019.110248
Wang J, Goyanes A, Gaisford S, Basit AW (2016) Stereolithographic (SLA) 3D printing of oral modified-release dosage forms. Int J Pharm 503:207–212. https://doi.org/10.1016/j.ijpharm.2016.03.016
Xenikakis I, Tzimtzimis M, Tsongas K, Andreadis D, Demiri E, Tzetzis D, Fatouros DG (2019) Fabrication and finite element analysis of stereolithographic 3D printed microneedles for transdermal delivery of model dyes across human skin in vitro. Eur J Pharm Sci 137:104976. https://doi.org/10.1016/j.ejps.2019.104976
Xu X, Robles-Martinez P, Madla CM, Joubert F, Goyanes A, Basit AW, Gaisford S (2020) Stereolithography (SLA) 3D printing of an antihypertensive polyprintlet: case study of an unexpected photopolymer-drug reaction. Addit Manuf 33:101071. https://doi.org/10.1016/j.addma.2020.101071
Xu X, Awad A, Robles-Martinez P, Gaisford S, Goyanes A, Basit AW (2021a) Vat photopolymerization 3D printing for advanced drug delivery and medical device applications. J Control Release 329:743–757. https://doi.org/10.1016/j.jconrel.2020.10.008
Xu X, Goyanes A, Trenfield SJ, Diaz-Gomez L, Alvarez-Lorenzo C, Gaisford S, Basit AW (2021b) Stereolithography (SLA) 3D printing of a bladder device for intravesical drug delivery. Mater Sci Eng C 120:111773. https://doi.org/10.1016/j.msec.2020.111773
Xu L, Yang Q, Qiang W, Li H, Zhong W, Pan S, Yang G (2021c) Hydrophilic excipient-independent drug release from SLA-printed pellets. Pharmaceutics 13:1–15. https://doi.org/10.3390/pharmaceutics13101717
Zitelli G, Reichental AN, Tringali L (2022) Methods for photo-curing with displaceable self-lubricating substratum for the formation of three-dimensional objects, US 11,260,579 B2
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2023 The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd.
About this chapter
Cite this chapter
Ravi, P., Patel, P. (2023). Stereolithography (SLA) in Pharmaceuticals. In: Banerjee, S. (eds) Additive Manufacturing in Pharmaceuticals. Springer, Singapore. https://doi.org/10.1007/978-981-99-2404-2_3
Download citation
DOI: https://doi.org/10.1007/978-981-99-2404-2_3
Published:
Publisher Name: Springer, Singapore
Print ISBN: 978-981-99-2403-5
Online ISBN: 978-981-99-2404-2
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)