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

Abstract

ABSTRACTBackground: 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.