Low-temperature FDM 3D printing of immediate-release glipizide tablets: formulation optimization, solid-state...

Glipizide (GPZ), a biopharmaceutics classification system Class II antidiabetic drug with low aqueous solubility and a high melting point, presents challenges for fused deposition modeling (FDM) 3D printing due to the elevated processing temperatures commonly required. This study investigated low-temperature hot-melt extrusion (HME) and FDM 3D printing for the fabrication of personalized immediate-release GPZ tablets using vinylpyrrolidone-vinyl acetate copolymer (KVA64)-based filaments. GPZ-loaded filaments containing KVA64, mannitol (MAN), and triethyl citrate (TEC) were successfully prepared at 60 °C and printed at 90 °C. Among six formulations investigated, the filament composed of 12% w/w GPZ, 69% w/w KVA64, 10% w/w MAN, and 9% w/w TEC exhibited suitable flexibility, feedability, and moisture resistance. DSC, PXRD, and TGA findings were consistent with a partially amorphous GPZ dispersion containing residual crystalline domains, with no detectable thermal degradation under the processing conditions. A mixed-level factorial design was used to investigate the effects of infill pattern, number of shells, and layer thickness on GPZ release at 10 min. After Bonferroni adjustment for multiple comparisons, infill pattern, number of shells, and the infill pattern × layer thickness interaction remained statistically significant, whereas the main effect of layer thickness did not. Grid infill and fewer shells generally promoted faster drug release, while the effect of layer thickness depended on the infill architecture. Dose-adjusted tablets containing 5, 7.5, 10, and 15 mg GPZ were produced by modifying tablet thickness while maintaining a constant diameter. Thinner tablets exhibited faster dissolution because of their higher surface area-to-volume ratios. However, the 15 mg tablet did not meet the immediate-release dissolution criterion at 30 min, indicating that height-based scaling alone is insufficient for maintaining immediate-release performance at higher doses. These findings demonstrate the potential of low-temperature HME-FDM printing for personalized GPZ tablets while emphasizing the need to optimize both tablet geometry and internal architecture across the intended dose range.