International Journal of Drug Delivery Technology
Volume 14, Issue 2

A Novel Process for Improving the Drug Loading of Highly Water- Soluble High-Dose Drug in FDM 3D Printed Tablets

Adarsh Malgave1, Rajkumar Malayandi1*, Anumol Joseph1, Sideequl Akbar1, Vinod Gaikwad1, Subramanian Natesan2, Ravichandiran V1,2

1Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research Hajipur, Export Promotion Industrial Park, Hajipur, Bihar, India.

2Advanced Formulation Laboratory, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research Kolkata, Kolkata, India. 

Received: 28th April, 2024; Revised: 19th May, 2024; Accepted: 21st May, 2024; Available Online: 25th June, 2024 

ABSTRACT

Background: 3D printing technologies, also known as additive manufacturing technologies, are gaining importance in pharmaceutical research and manufacturing. These technologies are widely used in automobile, plastic, and material fabrication industries. In the recent past, pharmaceutical industries are actively working to increase the applicability of these technologies in commercial manufacturing. On the other hand, clinics and hospitals are ready to adopt these technologies due to their versatility such as flexibility, individual customization, and low-cost investment. FDM 3D printing technology is one of the widely used technologies for the manufacturing of finished products. However, this technology has limitations such as drug loading, scale-up issues, and regulatory requirements. The present study focused on developing a suitable solvent system along with a drug-loading method to increase the industrial applicability of this technology.

Methods: Metformin, a high-dose, highly soluble drug, was selected as a model. Solvents such as water, ethanol, and methanol and their combinations were explored. Saturation solubility and drug loading in both PVA filaments and printed tablets were tested for drug loading. The solvent ratio of ethanol/methanol/water (8:1:1) was selected. The different infills of 10, 25, 50, 75, and 100% were printed using PVA filaments and were subjected to drug loading using soaking and solvent curing methods.

Results: The soaking method has resulted in poor drug loading as well as layer separation and swelling of the polymer. The solvent curing method has a maximum drug loading of 91.9% w/w without physical deformities of the tablets. Moreover, the solvent curing method is a scalable process with less process time, and hence this method could be useful for both large-scale commercial manufacturing as well as customized formulations for personalized therapies.

Conclusion: This method could be used for manufacturing thermoliable drug products and moderate-dose drug substances. Based on the research outcomes, we propose a novel, scalable, and rapid solvent-curing method for drug loading in the FDM 3D printing technique.

Keywords: Metformin, 3D printing, Drug loading, Tablet, Immediate release. International Journal of Drug Delivery Technology (2024); DOI: 10.25258/ijddt.14.2.22

How to cite this article: Malgave A, Malayandi R, Joseph A, Akbar S, Gaikwad V, Natesan S, Ravichandiran V. A Novel Process for Improving the Drug Loading of Highly Water-Soluble High-Dose Drug in FDM 3D Printed Tablets. International Journal of Drug Delivery Technology. 2024;14(2):737-743.

REFERENCES

  1. Rouf S, Malik A, Singh N, et al. Additive manufacturing technologies: Industrial and medical applications. Sustain Oper Comput. 2022;3:258-274. doi:10.1016/J.SUSOC.2022.05.001
  2. Vaz VM, Kumar L. 3D Printing as a Promising Tool in Personalized Medicine. AAPS PharmSciTech. 2021;22(1):1-20. doi:10.1208/S12249-020-01905-8/TABLES/3
  3. Kruk ME, Gage AD, Arsenault C, et al. High-quality health systems in the Sustainable Development Goals era: time for a Lancet Glob Heal. 2018;6(11):e1196. doi:10.1016/ S2214-109X(18)30386-3
  4. Marín-Peñalver JJ, Martín-Timón I, Sevillano-Collantes C, Cañizo-Gómez FJ Update on the treatment of type 2 diabetes mellitus. World J Diabetes. 2016;7(17):354. doi:10.4239/WJD. V7.I17.354
  5. Brown MT, Bussell Medication Adherence: WHO Cares
  6. Mayo Clin Proc. 2011;86(4):304. doi:10.4065/MCP.2010.0575
  7. Jamróz W, Szafraniec J, Kurek M, Jachowicz R. 3D Printing in Pharmaceutical and Medical Applications – Recent Achievements and Challenges. Pharm Res. 2018;35(9). doi:10.1007/S11095-018- 2454-X
  8. Ser rano DR , Kara A, Yuste I , et 3D Pr i nt i ng Technologies in Personalized Medicine, Nanomedicines, and Biopharmaceuticals. Pharmaceutics. 2023;15(2). doi:10.3390/ PHARMACEUTICS15020313
  9. Javaid M, Haleem A, Singh RP, Suman 3D printing applications for healthcare research and development. Glob HeaJ. 2022;6(4):217-226. doi:10.1016/J.GLOHJ.2022.11.001
  10. FDA’s Regulatory Framework for 3D Printing of Medical Devices at the Point of Care Needs More Clarity. Accessed November 3, 2023. https://www.pewtrusts.org/en/research-and- analysis/issue-briefs/2022/07/fdas-regulatory-framework-for-3d- printing-of-medical-devices-needs-more-clarity
  11. Cano-Vicent A, Tambuwala MM, Hassan SS, et al. Fused deposition modelling: Current status, methodology, applications and future Addit Manuf. 2021;47:102378. doi:10.1016/J. ADDMA.2021.102378
  12. Tagami T, Kuwata E, Sakai N, Ozeki T. Drug incorporation into polymer filament using simple soaking method for tablet preparation using fused deposition modeling. Biol Pharm Bull. 2019;42(10):1753-1760. doi:10.1248/bpb.b19-00482
  13. Goyanes A, Buanz ABM, Hatton GB, Gaisford S, Basit 3D printing of modified-release aminosalicylate (4-ASA and 5-ASA) tablets. Eur J Pharm Biopharm. 2015;89:157-162. doi:10.1016/j. ejpb.2014.12.003
  14. Li Chew S, de Mohac LM, Raimi-Abraham 3D-Printed Solid Dispersion Drug Products. Pharmaceutics. 2019;11(12):1-12. doi:10.3390/pharmaceutics11120672
  15. Qamar N, Abbas N, Irfan M, et al. Personalized 3D printed ciprofloxacin impregnated meshes for the management of hernia. J Drug Deliv Sci Technol. 2019;53(June):101164. doi:10.1016/j. 2019.101164
  16. Malayandi R, Malgave A, Gaikwad V, Peraman R, Aishwarya D, Ravichandiran V. Understanding the influence of thermal cycles on the stability of metformin HCl in presence of Sitagliptin phosphate monohydrate and polyvinyl alcohol. J Therm Anal Calorim 2023. Published online November 15, 2023:1-15. doi:10.1007/S10973-023-12639-7
  17. International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use Impurities: Guideline for Residual SolventsQ3C(R8).
  18. Reginster JY, Neuprez A, Lecart MP, Sarlet N, Bruyere Role of glucosamine in the treatment for osteoarthritis. Rheumatol Int. 2012;32(10):2959. doi:10.1007/S00296-012-2416-2
  19. Ibrahim M, Barnes M, McMillin R, et al. 3D Printing of Metformin HCl PVA Tablets by Fused Deposition Modeling: Drug Loading, Tablet Design, and Dissolution Studies. AAPS PharmSciTech. 2019;20(5):3-13. doi:10.1208/s12249-019-1400-5
  20. Gioumouxouzis CI, Baklavaridis A, Katsamenis OL, et al. A 3D printed bilayer oral solid dosage form combining metformin for prolonged and glimepiride for immediate drug Eur J Pharm Sci. 2018;120:40-52. doi:10.1016/J.EJPS.2018.04.020
  21. Comparison of FDA and WHO Definitions (Continued). Published online 2011. Accessed November 17, 2023. http://www. gov/cder/guidance/3618fnl.htm,
  22. Ono A, Kurihara R, Terada K, Suganod K. Bioequivalence Dissolution Test Criteria for Formulation Development of High Solubility-Low Permeability Chem Pharm Bull (Tokyo). 2023;71(3):213-219. doi:10.1248/CPB.C22-00685