Kinetics‐By‐Design: On‐Demand Fabrication of Personalized Drug‐Release Profiles Using Multi‐Material 3D Printing

ABSTRACT Controlling the release of highly water‐soluble narrow therapeutic index (NTI) drugs remains a fundamental challenge, as intrinsic solubility dominates dissolution and limits kinetic programmability. Conventional dosage forms and current 3D‐printed systems cannot overcome this barrier due to pH sensitivity, ionization, hydrodynamics, and drying‐induced geometric defects. We used 4‐aminopyridine as a model NTI drug to establish a three‐tier “kinetics‐by‐design” framework that encodes release through architecture rather than composition. First, a buffered, non‐eroding drug‐loaded structure (DLS) eliminated pH dependence, corrected the drying‐induced frustum effect, and achieved highly reproducible fabrication (drug uniformity RSD = 0.81%; weight RSD across 80 tablets = 1.42%). This isotropic platform further enabled personalized release within 4 h by tuning surface‐area/volume ratios. Second, barrier‐guided printlets (BGPs) imposed anisotropic diffusion, converting path length and release area into programmable variables and achieving predictable sustained release over 8–20 h, accurately described by a universal model (R 2 = 0.992). Third, path‐modulated printlets (PMPs) introduced internal “kinetic gates” that enabled lag time adjustment and acceleration‐deceleration phases, achieving dynamic, full‐profile control. This architecture‐driven approach redefines drug release as a designable parameter, offering a scalable method for individualizing NTI drug therapy, chronic disease management, and the broader challenge of highly soluble compounds.