Development of an efficient approach to boost fused deposition modeling (FDM) printing of felodipine-HPMC tablets for enhanced physical stability.

Fused deposition modeling (FDM) is a widely investigated 3D printing technology for pharmaceutical applications because of its advantages, including easy access of equipment and cost-effectiveness. Despite its versatility, the FDM 3D printing process is multi-step, time-consuming and resource intensive, and requires a holistic selection of material and formulation design to achieve successful printing. The aim of this work is to develop an efficient approach to streamline FDM 3D tablet-printing processes, as well as to explore the factors that may influence the physical stability of the tablets produced. For this purpose, the polymer Affinisol™ HPMC HME 15LV and the model drug felodipine were selected for printing process evaluation, and the produced drug-polymer tablets were investigated for printing quality and physical stability. The approach began with a material-based rheological study to predict the processing temperature range for the hot melt extrusion process which was used to produce the required filament feedstock for FDM 3D printing. Flory-Huggins (F-H) theory and phase diagram were applied to guide the expected drug-polymer system physical stability with various ratios under different temperatures, suggesting that the system would be unstable when the weight fraction of felodipine is greater than 0.3. Based on these analyses, FDM 3D printed tablets with varying drug loads, printing temperatures, and infill densities were produced, and the long-term physical stability of the printed tablets under different conditions was monitored using XRD, DSC and polarized light microscopy. The results of the extrusion and printing process, as well as the observed long-term physical stability, were consistent with the findings from the predictions from the rheological study and theoretical evaluations. This suggests that an approach which combines rheological studies, theoretical evaluations and phase diagram construction could be applied as a pre-screen and optimization strategy, removing the need for full material characterization prior to FDM 3D printing of medicine. Such an approach significantly minimizes the amount of drug required, accelerates excipient selection, and optimizes the process for pharmaceutical manufacturing using FDM 3D printing. Furthermore, this methodology holds promise for broader application in other material-based FDM printing processes, offering a versatile framework for optimizing printing quality and stability across diverse systems.