Stability of Medicinal Nanoemulsions to Spaceflight: Insights From the StarMed Experiment.

Space missions require liquid drug formulations that remain physically stable and exhibit predictable release under launch, microgravity, and handling stresses. This study examined melatonin‑loaded nanoemulsions flown on the MAPHEUS‑15 sounding rocket, comparing an uncoated nanoemulsion (MN) with a chitosan‑coated nanoemulsion (CCN). Droplet size, polydispersity index (PDI), and zeta potential were measured at Day 0 and after spaceflight, ground vibration testing, matched ground controls, and laboratory storage. Melatonin release was quantified by dynamic dialysis and interpreted using a compartmental mass-transfer model. Melatonin‑loaded nanoemulsion (MN) showed a modest, systematic increase in droplet size under all post‑experiment conditions, with unchanged PDI and zeta potential, consistent with time‑dependent coalescence and Ostwald ripening rather than a specific microgravity effect. CCN maintained essentially unchanged droplet size, PDI, and zeta potential, indicating interfacial steric stabilization by chitosan. For MN, ageing and sounding‑rocket exposure increased the apparent fraction of melatonin available to the aqueous phase, but normalized release profiles overlapped when scaled to the fitted maximum releasable fraction, suggesting unchanged intrinsic release kinetics. In CCN, both the accessible fraction and the release profile were preserved. Overall, chitosan coating enhanced dimensional and release stability, supporting interfacial polymer coatings as a strategy for robust liquid pharmaceutical formulations for future space medicine.