Semi-solid extrusion 3D printing for personalized drug delivery: rheology, printability, and pharmaceutical...

Conventional pharmaceutical manufacturing is optimized for standardized fixed-dose products and offers limited flexibility for patients requiring individualized dosing, patient-acceptable dosage forms, or multidrug therapy. Semi-solid extrusion (SSE) 3D printing can process gels, pastes, suspensions, and other viscoelastic formulations under mild thermal conditions to produce dosage forms with digitally controlled dose, geometry, and drug-release behavior. This review summarizes recent advances in pharmaceutical SSE 3D printing from formulation, process, application, and translational perspectives. Key rheological determinants of printability are discussed, including yield-related behavior, shear-thinning behavior, viscoelasticity, and structural recovery, which collectively influence extrudability, filament deposition, shape retention, and structural fidelity. Current printability assessment strategies are also reviewed, with emphasis on linking ink properties and printing parameters to critical quality attributes such as dimensional accuracy, content uniformity, mechanical integrity, dissolution and drug-release performance, and stability. Pharmaceutical applications are discussed in individualized dose adjustment, structure-mediated release modulation, medicines for pediatric and older adult, non-oral and local delivery systems, implantable formulations, and multidrug products. Finally, translational requirements are considered, including validated digital workflows, qualified manufacturing processes, process analytical technologies, appropriate quality monitoring, microbial control, packaging, and auditable regulatory documentation. Overall, SSE 3D printing represents a promising platform with substantial potential for personalized drug delivery, although broader clinical implementation will require stronger clinical, regulatory, and health-economic evidence.