Abstract
The application of machine learning and deep learning in additive manufacturing, also called 3D printing, is expected in industrial fields to be an effective method to optimize the manufacturing process, to control the quality of 3D printed objects, to detect defects in the objects, and to predict material properties. In the pharmaceutical field, 3D printed medicine has been approved by the United States Food and Drug Administration, and since then, 3D printing technology has been attracting attention, even creating a new model of tailored medicine. The 3D printing of pharmaceutical products needs a trial-and-error process due to the complex printing parameters as well as the physical properties of the printer ink, which is the drug formulation in this case. Machine learning may hold promise in solving the complex problems of drug manufacturing using 3D printers. This review introduces recent articles about 3D printed medicine and the application of machine learning. We also include recent articles about 3D printed medicine that use statistical approaches in the experimental methods. Finally, we discuss a possible future where “artificial intelligence pharmacists” will regularly use 3D printers in a clinical setting.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Aita IE, Rahman J, Breitkreutz J, Quodbach J (2020) 3D-printing with precise layer-wise dose adjustments for paediatric use via pressure-assisted microsyringe printing. Eur J Pharm Biopharm 157:59–65. https://doi.org/10.1016/j.ejpb.2020.09.012
Alayoubi A, Zidan A, Asfari S, Ashraf M, Sau L, Kopcha M (2022) Mechanistic understanding of the performance of personalized 3D-printed cardiovascular polypills: a case study of patient-centered therapy. Int J Pharm 617:121599. https://doi.org/10.1016/j.ijpharm.2022.121599
Anderspuk H, Viidik L, Olado K, Kogermann K, Juppo A, Heinämäki J, Laidmäe I (2021) Effects of crosslinking on the physical solid-state and dissolution properties of 3D-printed theophylline tablets. Ann 3D Print Med 4:100031. https://doi.org/10.1016/j.stlm.2021.100031
Arafat B, Qinna N, Cieszynska M, Forbes RT, Alhnan MA (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 128:282–289. https://doi.org/10.1016/j.ejpb.2018.04.010
Araújo MRP, Sa-Barreto LL, Gratieri T, Gelfuso GM, Cunha-Filho M (2019) The digital pharmacies era: how 3D printing technology using fused deposition modeling can become a reality. Pharmaceutics 11:128. https://doi.org/10.3390/pharmaceutics11030128
Ayyoubi S, Cerda JR, Fernández-García R, Knief P, Lalatsa A, Healy AM, Serrano DR (2021) 3D printed spherical mini-tablets: geometry versus composition effects in controlling dissolution from personalised solid dosage forms. Int J Pharm 597:120336. https://doi.org/10.1016/j.ijpharm.2021.120336
Batson S, Mitchell SA, Lau D, Canobbio M, de Goede A, Singh I, Loesch U (2020) Automated compounding technology and workflow solutions for the preparation of chemotherapy: a systematic review. Eur J Hosp Pharm 27:27. https://doi.org/10.1136/ejhpharm-2019-001948
Butler KT, Davies DW, Cartwright H, Isayev O, Walsh A (2018) Machine learning for molecular and materials science. Nature 559:547–555. https://doi.org/10.1038/s41586-018-0337-2
Castro BM, Elbadawi M, Ong JJ, Pollard T, Song Z, Gaisford S, Pérez G, Basit AW, Cabalar P, Goyanes A (2021) Machine learning predicts 3D printing performance of over 900 drug delivery systems. J Control Release 337:530–545. https://doi.org/10.1016/j.jconrel.2021.07.046
Cerda JR, Arifi T, Ayyoubi S, Knief P, Ballesteros MP, Keeble W, Barbu E, Healy AM, Lalatsa A, Serrano DR (2020) Personalised 3D printed medicines: optimising material properties for successful passive diffusion loading of filaments for fused deposition modelling of solid dosage forms. Pharmaceutics 12:345. https://doi.org/10.3390/pharmaceutics12040345
Char DS, Shah NH, Magnus D (2018) Implementing machine learning in health care -addressing ethical challenges. N Engl J Med 378:981–983. https://doi.org/10.1056/NEJMp1714229
Chen IY, Pierson E, Rose S, Joshi S, Ferryman K, Ghassemi M (2021) Ethical machine learning in healthcare. Annu Rev Biomed 4:123–144. https://doi.org/10.1146/annurev-biodatasci-092820-114757
Crișan AG, Iurian S, Porfire A, Rus LM, Bogdan C, Casian T, Lucacel RC, Turza A, Porav S, Tomuță I (2022) QbD guided development of immediate release FDM-3D printed tablets with customizable API doses. Int J Pharm 613:121411. https://doi.org/10.1016/j.ijpharm.2021.121411
Das S, Dey R, Nayak AK (2021) Artificial intelligence in pharmacy. Indian J Pharm Educ Res 55:304–318. https://doi.org/10.5530/ijper.55.2.68
Davenport T, Kalakota R (2019) The potential for artificial intelligence in healthcare. Future Healthc J 6:94–98. https://doi.org/10.7861/futurehosp.6-2-94
Delli U, Chang S (2018) Automated process monitoring in 3D printing using supervised machine learning. Procedia Manuf 26:865–870. https://doi.org/10.1016/j.promfg.2018.07.111
Dos Santos J, Deon M, da Silva GS, Beck RCR (2021) Multiple variable effects in the customization of fused deposition modelling 3D-printed medicine: a design of experiment (DoE) approach. Inf J Pharm 597:120331. https://doi.org/10.1016/j.ijpharm.2021.120331
Elbadawi M, Muñiz Castro B, Gavins FKH, Ong JJ, Gaisford S, Pérez G, Basit AW, Cabalar P, Goyanes A (2020a) M3DISEEN: a novel machine learning approach for predicting the 3D printability of medicines. Int J Pharm 590:119837. https://doi.org/10.1016/j.ijpharm.2020.119837
Elbadawi M, Gustaffson T, Gaisford S, Basit AW (2020b) 3D printing tablets: predicting printability and drug dissolution from rheological data. Int J Pharm 590:119868. https://doi.org/10.1016/j.ijpharm.2020.119868
Galande AD, Khurana NA, Mutalik S (2020) Pediatric dosage forms—challenges and recent developments: a critical review. J Appl Pharm Sci 10:155–166. https://doi.org/10.7324/JAPS.2020.10718
Goyanes A, Madla CM, Umerji A, Piñeiro GD, Montero JMG, Diaz MJL, Miguel Barcia G, Taherali F, Sánchez-Pintos P, Couce ML, Gaisford S, Basit AW (2019) Automated therapy preparation of isoleucine formulations using 3D printing for the treatment of MSUD: first single-Centre, prospective, crossover study in patients. Int J Pharm 567:118497. https://doi.org/10.1016/j.ijpharm.2019.118497
Hamed R, Mohamed EM, Rahman Z, Khan MA (2021) 3D-printing of lopinavir printlets by selective laser sintering and quantification of crystalline fraction by XRPD-chemometric models. Int J Pharm 592:120059. https://doi.org/10.1016/j.ijpharm.2020.120059
Han X, Kang D, Liu B, Zhang H, Wang Z, Gao X, Zheng A (2022) Feasibility of developing hospital preparation by semisolid extrusion 3D printing: personalized amlodipine besylate chewable tablets. Pharm Dev Technol 27:164–174. https://doi.org/10.1080/10837450.2022.2027965
Henry S, Vadder LD, Decorte M, Francia S, Steenkiste MV, Saevels J, Vanhoorne V, Vervaet C (2021) Development of a 3D-printed dosing platform to aid in zolpidem withdrawal therapy. Pharmaceutics 13:1684. https://doi.org/10.3390/pharmaceutics13101684
Herrada-Manchón H, Rodríguez-González D, Fernández MA, Suñé-Pou M, Pérez-Lozano P, García-Montoya E (2020) Enrique Aguilar 53D printed gummies: personalized drug dosage in a safe and appealing way. Int J Pharm 587:119687. https://doi.org/10.1016/j.ijpharm.2020.119687
Ilyas RA, Sapuan SM, Harussani MM, Hakimi MYAY, Haziq MZM, Atikah MSN, Asyraf MRM, Ishak MR, Razman MR, Nurazzi NM, Norrrahim MNF, Abral H, Asrofi M (2021) Polylactic acid (PLA) biocomposite: processing, additive manufacturing and advanced applications. Polymers 13:1326. https://doi.org/10.3390/polym13081326
Jamróz W, Szafraniec J, Kurek M, Jachowicz R (2018) 3D printing in pharmaceutical and medical applications—recent achievements and challenges. Pharm Res 35:176. https://link.springer.com/article/10.1007/s11095-018-2454-x
Jin Z, Zhang Z, Gu GX (2019) Autonomous in-situ correction of fused deposition modeling printers using computer vision and deep learning. Manuf Lett 22:11–15. https://doi.org/10.1016/j.mfglet.2019.09.005
Khaled SA, Burley JC, Alexander MR, Yang J, Roberts CJ (2015) 3D printing of five-in-one dose combination polypill with defined immediate and sustained release profiles. J Control Release 217:308–314. https://doi.org/10.1016/j.jconrel.2015.09.028
Khorasani M, Edinger M, Raijada D, Bøtker J, Aho J, Rantanen J (2016) Near-infrared chemical imaging (NIR-CI) of 3D printed pharmaceuticals. Int J Pharm 515:324–330. https://doi.org/10.1016/j.ijpharm.2016.09.075
Kreft K, Lavrič Z, Stanić T, Perhavec P, Dreu R (2022) Influence of the binder jetting process parameters and binder liquid composition on the relevant attributes of 3D-printed tablets. Pharmaceutics 14:1568. https://doi.org/10.3390/pharmaceutics14081568
Li Z, Zhang Z, Shi J, Wu D (2019) Prediction of surface roughness in extrusion-based additive manufacturing with machine learning. Robot Comput Integr Manuf 57:488–495. https://doi.org/10.1016/j.rcim.2019.01.004
Macedo J, da Costa NF, Vanhoorne V, Vervaet C, Pinto JF (2022) The precision and accuracy of 3D printing of tablets by fused deposition modelling. J Pharm Sci 111:2814–2826. https://doi.org/10.1016/j.xphs.2022.05.006
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 11:544. https://doi.org/10.3390/pharmaceutics11100544
Mahesh B (2020) Machine learning algorithms—a review. Int J Sci Res 9:381–386. https://www.ijsr.net/get_abstract.php?paper_id=ART20203995
Martinez PR, Goyanes A, Basit AW, Gaisford S (2018) Influence of geometry on the drug release profiles of stereolithographic (SLA) 3D-printed tablets. AAPS PharmSciTech 19:3355–3361. https://link.springer.com/article/10.1208/s12249-018-1075-3
Melocchi A, Uboldi M, Maroni A, Foppoli A, Palugan L, Zema L, Gazzaniga A (2020) 3D printing by fused deposition modeling of single- and multi-compartment hollow systems for oral delivery—a review. Int J Pharm 579:119155. https://doi.org/10.1016/j.ijpharm.2020.119155
Meng L, McWilliams B, Jarosinski W, Park HY, Jung YG, Lee J, Zhang J (2020) Machine learning in additive manufacturing: a review. JOM 72:2363–2377. https://doi.org/10.1007/s11837-020-04155-y
Nasereddin JM, Wellner N, Alhijjaj M, Belton P, Qi S (2018) Development of a simple mechanical screening method for predicting the feedability of a pharmaceutical FDM 3D printing filament. Pharm Res 35:151. https://link.springer.com/article/10.1007/s11095-018-2432-3#Sec1
Norman J, Madurawe RD, Moore CM, Khan MA, Khairuzzaman A (2017) A new chapter in pharmaceutical manufacturing: 3D-printed drug products. Adv Drug Deliv Rev 108:39–50. https://doi.org/10.1016/j.addr.2016.03.001
Öblom H, Sjöholm E, Rautamo M, Sandler N (2019) Towards printed pediatric medicines in hospital pharmacies: comparison of 2D and 3D-printed orodispersible warfarin films with conventional oral powders in unit dose sachets. Pharmaceutics 11:334. https://doi.org/10.3390/pharmaceutics11070334
Ong JJ, Castro BM, Gaisford S, Cabalar P, Basit AW, Pérez G, Goyanes A (2022) Accelerating 3D printing of pharmaceutical products using machine learning. Int J Pharm X 4:100120. https://doi.org/10.1016/j.ijpx.2022.100120
Palekar S, Nukala PK, Mishra SM, Kipping T, Patel K (2019) Application of 3D printing technology and quality by design approach for development of age-appropriate pediatric formulation of baclofen. Int J Pharm 556:106–116. https://doi.org/10.1016/j.ijpharm.2018.11.062
Pereira BC, Isreb A, Forbes RT, Dores F, Habashy R, Petit JB, Alhnan MA, Oga EF (2019) ‘Temporary Plasticiser’: a novel solution to fabricate 3D printed patient-centred cardiovascular ‘Polypill’ architectures. Eur J Pharm Biopharm 135:94–103. https://doi.org/10.1016/j.ejpb.2018.12.009
Pietrzak K, Isreb A, Alhnan MA (2015) A flexible-dose dispenser for immediate and extended release 3D printed tablets. Eur J Pharm Biopharm 96:380–387. https://doi.org/10.1016/j.ejpb.2015.07.027
Pires FQ, Alves-Silva I, Pinho LAG, Chaker JA, Sa-Barreto LL, Gelfuso GM, Gratieri T, Cunha-Filho M (2020) Predictive models of FDM 3D printing using experimental design based on pharmaceutical requirements for tablet production. Int J Pharm 588:119728. https://doi.org/10.1016/j.ijpharm.2020.119728
Qi X, Chen G, Li Y, Cheng X, Li C (2019) Applying neural-network-based machine learning to additive manufacturing: current applications, challenges, and future perspectives. Engineering 5:721–729. https://doi.org/10.1016/j.eng.2019.04.012
Rycerz K, Stepien KA, Czapiewska M, Arafat BT, Habashy R, Isreb A, Peak A, Alhnan MA (2019) Embedded 3D printing of novel bespoke soft dosage form concept for pediatrics. Pharmaceutics 11:630. https://doi.org/10.3390/pharmaceutics11120630
Sadia M, Arafat B, Ahmed W, Forbes RT, Alhnan MA (2018) Channelled tablets: an innovative approach to accelerating drug release from 3D printed tablets. J Control Release 269:355–363. https://doi.org/10.1016/j.jconrel.2017.11.022
Samaro A, Shaqour B, Goudarzi NM, Ghijs M, Cardon L, Boone MN, Verleije B, Beyers K, Vanhoorne V, Cos P, Vervaet C (2021) Can filaments, pellets and powder be used as feedstock to produce highly drug-loaded ethylene-vinyl acetate 3D printed tablets using extrusion-based additive manufacturing? Int J Pharm 6-7:120922. https://doi.org/10.1016/j.ijpharm.2021.120922
Sarabi MR, Alseed MM, Karagoz AA, Tasoglu S (2022) Machine learning-enabled prediction of 3D-printed microneedle features. Biosensors 12:491. https://doi.org/10.3390/bios12070491
Scoutaris N, Ross SA, Douroumis D (2018) D Printed “starmix” drug loaded dosage forms for paediatric applications. Pharm Res 35:34. https://link.springer.com/article/10.1007/s11095-017-2284-2
Stanojević G, Medarević D, Adamov I, Pešić N, Kovačević J, Ibrić S (2021) Tailoring atomoxetine release rate from DLP 3D-printed tablets using artificial neural networks: influence of tablet thickness and drug loading. Molecules 26:111. https://doi.org/10.3390/molecules26010111
Tabriz AG, Scoutaris N, Gong Y, Hui HW, Kumar S, Douroumis D (2021) Investigation on hot melt extrusion and prediction on 3D printability of pharmaceutical grade polymers. Int J Pharm 604:120755. https://doi.org/10.1016/j.ijpharm.2021.120755
Tagami T, Kuwata E, Sakai N, Ozeki T (2019) Drug incorporation into polymer filament using simple soaking method for tablet preparation using fused deposition modeling. Biol Pharm Bull 42:1753–1760. https://doi.org/10.1248/bpb.b19-00482
Tagami T, Ito E, Kida R, Hirose K, Noda T, Ozeki T (2021a) 3D printing of gummy drug formulations composed of gelatin and an HPMC-based hydrogel for pediatric use. Int J Pharm 594:120118. https://doi.org/10.1016/j.ijpharm.2020.120118
Tagami T, Morimura C, Ozeki T (2021b) Effective and simple prediction model of drug release from “ghost tablets” fabricated using a digital light projection-type 3D printer. Int J Pharm 604:120721. https://doi.org/10.1016/j.ijpharm.2021.120721
Trenfield SJ, Goyanes A, Telford R, Wilsdon D, Rowland M, Gaisford S, Basit AD (2018) 3D printed drug products: non-destructive dose verification using a rapid point-and-shoot approach. Int J Pharm 549:283–292. https://doi.org/10.1016/j.ijpharm.2018.08.002
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
Trenfield SJ, Tan HX, Goyanes A, Wilsdon D, Rowland M, Gaisford S, Basit AW (2020) Non-destructive dose verification of two drugs within 3D printed polyprintlets. Int J Pharm 577:119066. https://doi.org/10.1016/j.ijpharm.2020.119066
Vamathevan J, Clark D, Czodrowski P, Dunham I, Ferran E, Lee G, Li B, Madabhushi A, Shah P, Spitzer M, Zhao S (2019) Applications of machine learning in drug discovery and development. Nat Rev Drug Discov 18:463–477. https://doi.org/10.1038/s41573-019-0024-5
Vo AQ, Zhang J, Nyavanandi D, Bandari S, Repka MA (2020) Hot melt extrusion paired fused deposition modeling 3D printing to develop hydroxypropyl cellulose based floating tablets of cinnarizine. Carbohydr Polym 246:116519. https://doi.org/10.1016/j.carbpol.2020.116519
Walsh D, Serrano DR, Worku ZA, Norris BA, Healy AM (2018) Production of cocrystals in an excipient matrix by spray drying. Int J Pharm 536:467–477. https://doi.org/10.1016/j.ijpharm.2017.12.020
Wang Z, Li J, Hong X, Han X, Liu B, Li X, Zhang H, Gao J, Liu N, Gao X, Zheng A (2021) Taste masking study based on an electronic tongue: the formulation design of 3D printed levetiracetam instant-dissolving tablets. Pharm Res 38:831–842. https://link.springer.com/article/10.1007/s11095-021-03041-9
Zhu C, Tian Y, Zhang E, Gao X, Zhang H, Liu N, Han X, Sun Y, Wang Z, Zheng A (2022) Semisolid extrusion 3D printing of propranolol hydrochloride gummy chewable tablets: an innovative approach to prepare personalized medicine for pediatrics. AAPS PharmSciTech 23:166. https://link.springer.com/article/10.1208/s12249-022-02304-x
Zidan A, Alayoubi A, Coburn J, Asfari S, Ghammraoui B, Cruz CN, Ashraf M (2019a) Extrudability analysis of drug loaded pastes for 3D printing of modified release tablets. Int J Pharm 554:292–301. https://doi.org/10.1016/j.ijpharm.2018.11.025
Zidan A, Alayoubi A, Asfari S, Coburn J, Ghammraoui B, Aqueel S, Cruz CN, Ashraf M (2019b) Development of mechanistic models to identify critical formulation and process variables of pastes for 3D printing of modified release tablets. Int J Pharm 555:109–123. https://doi.org/10.1016/j.ijpharm.2018.11.044
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
Tagami, T., Ogawa, K., Ozeki, T. (2023). Machine Learning in Additive Manufacturing of Pharmaceuticals. In: Banerjee, S. (eds) Additive Manufacturing in Pharmaceuticals. Springer, Singapore. https://doi.org/10.1007/978-981-99-2404-2_11
Download citation
DOI: https://doi.org/10.1007/978-981-99-2404-2_11
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)