SYNERGISTIC OPTIMIZATION OF EUCALYPTUS OIL NANOEMULSIONS: PHYSICOCHEMICAL STABILITY AND CHEMICAL DEGRADATION PROFILES UNDER ACCELERATED STRESS
DOI:
https://doi.org/10.22159/ijap.2026v18i3.58299Keywords:
Eucalyptus oil nanoemulsion, Eucalyptol, Quality by design, Accelerated stability, Chemical degradationAbstract
Objective: To rationally design and optimize a eucalyptus oil nanoemulsion through a Quality by Design (QbD) framework while establishing an integrated dual-stability strategy that simultaneously interrogates physicochemical robustness and chemical integrity of eucalyptol under accelerated stress conditions.
Methods: Formulation optimization was performed using a full factorial experimental design (2⁴) to investigate the effects of surfactant proportion, cosurfactant proportion, surfactant type, and cosurfactant type on critical quality attributes (CQAs), including percent transmittance and viscosity. Statistical analysis was conducted using analysis of variance (ANOVA), followed by desirability function optimization. Physicochemical stability was evaluated through droplet size, polydispersity index (PDI), pH, viscosity, and visual observation, while chemical stability of eucalyptol was monitored using GC–MS during accelerated storage at 40±2 °C/75±5% RH for three months.
Results: The optimized nanoemulsion achieved high optical clarity (92.41%), low viscosity (27.59 cPs), and a desirability value of 0.972, with a statistically significant predictive model for transmittance (R² = 0.9987). The formulation maintained nanoscale droplet size (≈22–25 nm), low PDI (<0.30), stable pH, and absence of phase separation throughout storage. However, GC–MS analysis revealed a time-dependent decline in eucalyptol content despite preserved physicochemical stability, indicating a dissociation between droplet integrity and molecular retention.
Conclusion: The proposed integrated dual-stability framework advances current nanoemulsion development paradigms by demonstrating that physicochemical stability alone is insufficient for volatile therapeutic agents. Early incorporation of chemical stability evaluation is essential to achieve formulation reliability and translational relevance.
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