Glipizide (GPZ) is a BCS Class II antidiabetic drug with low aqueous solubility and a high melting point, which complicates conventional fused deposition modeling (FDM) 3D printing because of high processing temperatures. This study implemented a low-temperature hot-melt extrusion (HME) approach coupled with FDM to fabricate personalized immediate-release GPZ tablets.
Filaments were prepared at 60 °C and printed at 90 °C to minimize thermal exposure of the drug while maintaining filament feedability. The polymeric matrix employed was vinylpyrrolidone-vinyl acetate copolymer (KVA64) with mannitol (MAN) as an excipient and triethyl citrate (TEC) as a plasticizer. The overall aim was to generate filaments with acceptable mechanical properties and moisture resistance suitable for low-temperature FDM printing.
Six formulations were prepared and evaluated for extrusion and printability. The formulation identified as most suitable comprised 12% w/w GPZ, 69% w/w KVA64, 10% w/w MAN, and 9% w/w TEC. This filament demonstrated adequate flexibility, reliable feedability in the printer, and resistance to moisture, making it the lead composition for subsequent printing and characterization.
The low processing temperatures (60 °C for HME, 90 °C for printing) were explicitly chosen to avoid thermal degradation and to enable processing of a high-melting drug such as GPZ. The study reports successful filament production and printing at these temperatures for the selected formulation.
Differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and thermogravimetric analysis (TGA) were used to examine the physical state of GPZ within the printed matrices and to assess thermal stability under processing conditions.
Results from DSC and PXRD were consistent with a partially amorphous dispersion of GPZ in the KVA64-based filament and printed tablets, with residual crystalline domains detectable. TGA indicated no detectable thermal degradation of the drug or excipient system under the employed low-temperature HME and printing conditions. Together, these analyses support that the low-temperature process produced an amorphous-dominant but not fully amorphous drug distribution while maintaining thermal integrity.
A mixed-level factorial design was applied to investigate how FDM printing parameters influence early drug release, specifically GPZ release at 10 minutes. The factors tested were infill pattern, number of shells, and layer thickness. Statistical analysis included Bonferroni adjustment for multiple comparisons.
After correction, the following remained statistically significant predictors of release at 10 minutes: infill pattern, number of shells, and the interaction between infill pattern × layer thickness. The main effect of layer thickness alone was not significant after adjustment.
Empirical observations from the design indicated that a grid infill pattern and a lower shell count generally promoted faster drug release. However, the influence of layer thickness on dissolution rate was dependent on the chosen infill architecture; in some infill configurations, thinner or thicker layers changed porosity and pathway geometry in ways that either accelerated or slowed release.
These findings emphasize that internal architecture created by FDM — not just external geometry — substantially affects immediate-release performance and must be considered when designing printed tablets.
Dose-adjusted tablets containing 5, 7.5, 10, and 15 mg of GPZ were produced by varying tablet thickness while keeping tablet diameter constant. This height-based scaling method was intended to allow straightforward dose customization using the same printing parameters and filament composition.
Thinner tablets showed faster dissolution, which the authors attributed to higher surface area-to-volume ratios leading to increased exposure of the formulation to dissolution media. Despite this trend, the 15 mg tablet did not meet the defined immediate-release dissolution criterion at 30 minutes, demonstrating that simply increasing tablet height to achieve higher dose compromises the intended release profile.
This outcome indicates that height-based, diameter-constant scaling alone is insufficient to guarantee immediate-release behavior across a broad dose range. Adjustments to internal architecture (infill pattern, shell count, layer thickness), formulation composition, or other geometric parameters are necessary when targeting higher doses while preserving immediate-release performance.
The study demonstrates the feasibility of producing personalized immediate-release glipizide tablets using low-temperature HME followed by low-temperature FDM printing. The selected filament composition (12% GPZ, 69% KVA64, 10% MAN, 9% TEC) printed at 90 °C showed suitable mechanical and handling properties, and solid-state analyses indicated a partially amorphous drug dispersion without thermal degradation.
Crucially, tablet internal architecture — notably infill pattern and shell count — strongly influenced early drug release, and interactions between architecture and printing parameters affected release behavior. Simple height-based dose scaling failed for the highest dose tested (15 mg), underscoring the need to optimize both tablet geometry and internal print architecture across the intended dose range to maintain immediate-release performance.
Overall, low-temperature HME-FDM printing holds promise for personalized GPZ tablets, but successful translation will require integrated optimization of formulation, printer settings, and tablet design for each target dose.