In-use and long-term physicochemical, rheological and biopharmaceutical stability of 3D-printed inks and/or their...

The implementation of 3D printing technologies in clinical settings depends on formulations that are not only printable and compliant with quality standards but also physicochemical stable and reliable under real-use conditions. This study evaluated the in-use and long-term physicochemical and rheological stability of two hydrogel inks developed for semisolid extrusion (SSE) 3D printing: one containing pimobendan (PBD) and the other a placebo. PBD is a poorly water-soluble drug used to treat canine heart failure, whose formulation challenges highlight the potential of personalised drug delivery. Three batches of each formulation were stored in sterile syringes for 180 days to simulate clinical handling, reuse, and storage. Over time, the inks were assessed for rheology, printability, and reproducibility. Printlets produced from the PBD-loaded ink were also analysed for drug content and dissolution, comprising their physicochemical and biopharmaceutical stability. Despite repeated handling and ambient exposure, the PBD formulation maintained its structure, viscoelasticity, and printability, while the placebo showed a significant decline in viscosity. The drug-loaded ink remained suitable for 3D printing for up to six months, and the resulting printlets also remained stable during storage. These findings confirm the robustness of the PBD formulation and the importance of incorporating both the active pharmaceutical ingredient (API) and excipients directly into the ink. The placebo's instability supports the use of fully preloaded systems as a more reliable alternative. By simulating real-use conditions, this study offers a practical assessment of semisolid 3D printing inks, advancing beyond standard pharmacopeial tests and contributing to the establishment of relevant quality criteria for future clinical implementation. Future studies should focus on evaluating the microbiological stability of the printing inks under different storage conditions, including preservative system challenge tests to determine the most effective approach.