Microfluidic Engineering of Chitosan‐Coated Nanoemulsions for Controlled Release and Stability in Space Pharmaceutics

ABSTRACT Long‐duration exploration missions demand liquid medications that remain safe and effective without frequent resupply. We report a microfluidic‐assisted spontaneous emulsification strategy to produce an injectable, melatonin‐loaded oil‐in‐water nanoemulsion (MNE) and a chitosan‐coated variant (CCMN) engineered for space use. Medium‐chain triglyceride oil with an optimized Tween 80/Span 80 blend (hydrophilic‐lipophilic balance, HLB = 11) and glycerol as co‐surfactant yielded self‐emulsifying regions at low surfactant load, while in‐line chitosan coating of the droplets tuned interfacial mechanics. Formulations were screened by pseudo‐ternary phase diagrams and thermodynamic stress tests, characterized by dynamic Light Scattering (DLS), zeta potential, viscosity, pH and imaged by cryogenic transmission electron microscopy. The 0.25% chitosan coating produced small, narrowly distributed droplets (152 nm; polydispersity (PDI) = 0.16) with moderated surface charge and injection‐compatible viscosity, while uncoated controls were 172 nm. Under accelerated thermal stress (40°C–45°C; 28 d) CCMN limited size growth relative to uncoated nanoemulsions, and on a random positioning machine (0 g gravity‐vector‐average; 28 d) CCMN maintained size and polydispersity with no measurable coalescence; uncoated systems showed non‐destructive fluctuations. In vitro drug release followed the Weibull model for both formulations. CCMN showed sustained profile (∼65% at 12 h) relative to faster release from MNE (∼83% at 12 h).