Rheology-Driven Optimization of Semi-Solid Extrusion 3D Printing for High-Precision Personalized Dosage Forms

Semi-solid extrusion (SSE) three-dimensional printing has emerged as a transformative platform for personalized pharmaceutical manufacturing, particularly for thermolabile and dose-flexible formulations. Despite its growing clinical and industrial relevance, systematic rheology-driven optimization frameworks remain underdeveloped. This study establishes predictive rheological parameters governing print fidelity, dose precision, and structural integrity in SSE-fabricated dosage forms. Comprehensive rheological profiling, including viscosity, yield stress, shear-thinning behavior, and viscoelastic moduli, was correlated with extrudability, dimensional accuracy, drug content uniformity, and dissolution performance. Mathematical modeling based on the Herschel–Bulkley and power-law equations was employed to predict flow behavior under printing conditions. Structural stability was assessed using oscillatory rheometry and compression testing, while dissolution kinetics were modeled using Higuchi and Korsmeyer–Peppa’s equations. Results demonstrate that optimal print fidelity is achieved within a defined rheological window characterized by moderate yield stress, pronounced shear-thinning behavior, and rapid structural recovery post-extrusion. Drug uniformity was strongly influenced by polymer–drug interaction mechanisms and microstructural homogeneity. Compared with fused deposition modeling (FDM), SSE exhibited superior suitability for moisture-sensitive and low-dose drugs, although challenges in rheological standardization persist. The proposed predictive framework provides a mechanistic basis for standardizing SSE fabrication, thereby advancing regulatory alignment and clinical translation of personalized dosage forms.