Failure modes in semi-solid extrusion 3D printing for pharmaceuticals: from ink preparation to post-printing

Semi-solid extrusion (SSE) 3D printing, a type of syringe-based direct-ink writing, is increasingly being investigated for pharmaceutical dosage forms because of the possibility of low-temperature processing, multi-material architectures, and patient-specific designs. However, beyond feasibility, translation is limited by high process sensitivity; small changes in ink history, extrusion dynamics, deposition kinematics, and post-print solidification can cause defects that propagate to critical quality attributes (CQAs) such as mass and content uniformity (CU), mechanical integrity, disintegration, dissolution, and stability. Here, we organized pharmaceutical SSE failures in an end-to-end framework, from ink preparation, extrusion, deposition/build, and solidification/post-processing, and linked each failure family to dominant physical mechanisms (yield-stress fluid behavior, thixotropic recovery, nozzle-scale jamming/skin formation, pressure lag and compliance, and drying-driven stress and migration). A pragmatic diagnostics toolbox was synthesized, focusing on quick, discriminating signals that are achievable in small-batch settings (pressure/force traces, vision-based line-width proxies, gravimetric drift, and moisture/drying profiles). Finally, the failure taxonomy was converted into a failure mode and effects analysis (FMEA)-to-control plan template and a reproducibility checklist to enable cross-laboratory comparability and a clearer path towards controlled, audit-ready pharmaceutical SSE manufacturing.