Engineered Core-Shell Assemblies for Controlled Release of Gliclazide Using Fused Filament Fabrication (FFF)-3D Printing

In this study, innovative controlled-release core-shell assemblies were developed using hot-melt extrusion (HME) and fused filament fabrication (FFF) 3D printing. Cellulose acetate (CA) plasticized with 25% w/w triethyl citrate (TEC) and was extruded at 195 degrees C to produce filaments, which were then used to print hollow shells with varying orifice diameters on both upper and lower surfaces. Drug-loaded filaments for cores were generated by extruding Soluplus and SmartEx QD 100 (SmartEx) blends at 160 degrees C, incorporating gliclazide as a model drug. The resulting filaments were 3D printed into core structures, which were manually integrated into the pre-printed hollow shells to form complete core-shell assemblies. Comprehensive characterization of the 3D-printed cores via Fourier-transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC), and X-ray diffraction (XRD) confirmed the physical compatibility of the drug with polymers and the successful amorphization of the highly crystalline Biopharmaceutics Classification System (BCS) Class II drug gliclazide. Drug entrapment efficiency in all cores exceeded 80%. Scanning electron microscopy (SEM) was used to visualize the surface morphology of both the cores and shells, highlighting the structural variations with different orifice diameters. In vitro dissolution studies demonstrated that core-shell assemblies released the drug at a significantly slower rate than standalone cores, with varying lag phases attributed to controlled hydration through semi-permeable shell orifices. The ratio of Soluplus to SmartEx modulated the drug release mechanism, transitioning from diffusion in a swollen matrix to erosion-mediated release depending on the orifice size and core composition. Overall, these innovative core-shell systems incorporating multifunctional polymeric blends show promise for personalized therapies, offering controlled, chronotherapeutic, and osmotic drug delivery.