Optimized Low‐Temperature Ultrasonicated MK ‐7 Nanoemulsion: Characterization, Stability, and Bioavailability Potential

Menaquinone‐7 (MK‐7), a vital yet poorly bioavailable form of vitamin K 2 , requires advanced delivery systems to overcome its lipophilicity and instability. This study developed an optimized oil‐in‐water nanoemulsion (NE) for MK‐7 using a low‐temperature ultrasonication method. The formulation incorporated medium‐chain triglyceride (MCT) oil, a surfactant blend (Kolliphor RH 40 and Tween 20, 3:1), and tocopherol. A pseudo‐ternary phase diagram and Box–Behnken Design (BBD) were employed for systematic optimization. The optimized NE exhibited nanoscale droplets (21.1–27.3 nm by TEM), a low polydispersity index (PDI), and negative zeta potential. Comprehensive characterization via FT‐IR, DSC, XRD, and TEM/SEM confirmed successful MK‐7 encapsulation without chemical interaction, a reduction in crystallinity, and spherical droplet morphology. Stability studies over 86 days revealed excellent physical stability, but significant MK‐7 degradation occurred during ambient storage, decreasing from 52.46 μg/mL (100%) to ~47%–44% by days 35–50, then sharply to 6.2% by day 86, following zero‐order kinetics. The NE demonstrated promising in vitro pH‐dependent release, and in a rat model, altered pharmacokinetics of the MK‐7 NE showed lower C max and AUC with delayed T max at a low dose but higher C max and earlier T max at higher doses, indicating dose‐dependent absorption and exposure. This work presents a strategically designed NE that effectively addresses the physicochemical and absorption challenges of MK‐7, with oxidative stability identified as the pivotal hurdle for its translational development.