DESIGNING FIXED DOSE COMBINATION OF GLIPIZIDE AND FELODIPINE USING FUSED DEPOSITION MODELING 3D PRINTING

Abstract

Poor medication adherence in chronic diseases such as hypertension and diabetes affects approximately 50% of patients, primarily due to complex dosing regimens. This research investigated fused deposition modeling (FDM) 3D printing technology to develop personalized pharmaceutical dosage forms with controlled release profiles, comprising three studies: (i) controlled-release felodipine tablets with varying internal geometries, (ii) immediate-release glipizide tablets using low-temperature printing, and (iii) fixed-dose combination tablets incorporating both drugs. Drug-loaded filaments were prepared via hot-melt extrusion; felodipine filaments (5% w/w in PVA) were extruded at 185°C, while glipizide filaments (12% w/w with Kollidon® VA64, mannitol, triethyl citrate) required low-temperature processing at 60°C to preserve drug stability. 3D printing was performed using a dual-nozzle Flashforge Creator Pro at 195°C for felodipine and 90°C for glipizide. Characterization techniques included DSC, TGA, PXRD, SEM, and SRXTM analysis, and drug release was evaluated using followed USP dissolution methods with mathematical modeling. The first study revealed controlled-release felodipine tablets with constant volume but varying geometries (round, square, hexagonal, triangular) exhibited drug release governed by the surface area-to-volume (SA/V) ratios rather than surface area alone. Round geometry (SA/V=0.55) showed the fastest release, while triangular (SA/V=0.41) had the slowest. Peppas-Sahlin modeling confirmed swelling-controlled mechanisms, with polymer relaxation dominating (65-75%) over Fickian diffusion. Tablets with similar SA/V ratios demonstrated comparable dissolution profiles (f₂>50). The second study developed immediate-release glipizide tablets through factorial design optimization. Grid infill pattern, single shell, and 0.3 mm layer thickness provided optimal rapid release by maximizing porosity and surface contact. A mathematical model predicted tablet thickness for 5-15 mg dosages. All formulations achieved >80% release within 30 min, meeting USP criteria with ± 5% content uniformity. The third study produced fixed-dose combinations using three designs: stacked-layer, core-shell (felodipine core/glipizide shell), and inverted core-shell. All achieved dual-release profiles with immediate glipizide release (>80% at 30 min) and controlled felodipine release over 24 h. The stacked-layer showed the fastest felodipine release due to enhanced hydration, the core-shell demonstrated the slowest release following Hopfenberg erosion model, and the inverted core-shell produced glipizide profiles similar to commercial tablets (f₂=60.06). Key innovations include establishing predictive geometry-release relationships, achieving successful low-temperature processing for thermolabile drugs, and creating sophisticated dual-release polypills. This research demonstrates FDM 3D printing's potential for personalized medicine, enabling customized dosage forms tailared to individual patient needs, with precise control over drug release through geometric design and process optimization, and offers the potential to revolutionize pharmaceutical manufacturing via point-of-care production to improve patient compliance in chronic disease management.

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