Ali Abbas Abd Ali, Roswanira Abdul Wahab, Angham Tariq Ali, Evi Susanti, Ni Made Suaniti
Hyperpigmentation disorders such as melasma significantly impair quality of life, yet conventional treatments like hydroquinone pose considerable safety concerns that limit long-term use. To address this therapeutic challenge, we developed a safer alternative: a kinetically stable water-in-oil-in-water (W/O/W) double emulsion (DE) specifically engineered to enhance the topical delivery of kojic acid (KA), a depigmenting agent whose clinical efficacy is hindered by poor skin permeability. The optimized system comprised KA (1.0 w/w%), medium-chain triglyceride (18.0 w/w%), water (58.0 w/w%), and a Span 80:Tween 20 surfactant blend (16.6:83.4, HLB 14.6). Physicochemical characterization revealed a mean droplet size of 372 ± 9 nm and a polydispersity index of 0.21 ± 0.009, indicating a monodisperse population, while transmission electron microscopy revealed a spherical, nanosized morphology. Zeta potential measurements (−18.67 mV) suggested that steric, rather than electrostatic, mechanisms predominantly govern stability, attributable to the nonionic surfactant blend and xanthan gum. Our formulation demonstrated sustained, diffusion-dependent release following Higuchi kinetics (R2= 0.989–0.999), with 56–64% of KA released over 6 h under skin-relevant pH conditions (4.0–6.0). Rigorous stability testing, including centrifugation, freeze-thaw cycling, and 30-day storage at 4–35 °C, confirmed robustness against coalescence and Ostwald ripening. Conductivity (0.37 mS/cm) was consistent with an aqueous external phase and, when considered alongside the sustained-release profile and HLB-optimized two-step emulsification, supported the intended W/O/W architecture. Density functional theory calculations provided complementary molecular-level insights, revealing spontaneous, exothermic interactions between KA and Span 80 (binding energies: −7.009 to −13.036 kcal/mol) that are consistent with the favorable encapsulation and stability observed experimentally. Collectively, we successfully engineered a stable KA-loaded W/O/W DE system with sustained, diffusion-dependent release characteristics. The formulation’s physicochemical properties and stability profile support its potential as a topical delivery platform, warranting further investigation of skin permeation and clinical efficacy. © 2026 Taylor & Francis Group, LLC.
Department of Chemistry, Faculty of Science, Universiti Teknologi Malaysia, UTM Johor Bahru, Johor, Malaysia; Dhi Qar Health Department, Mohammed Al-Mousawi Children’s Hospital, Ministry of Health, Nasiriya Governorate, Iraq; Investigative and Forensic Sciences Research Group, Faculty of Science, Universiti Teknologi Malaysia, UTM Johor Bahru, Johor, Malaysia; Open Education College, Dhi Qar Branch, Iraqi Ministry of Education, Nasiriya Governorate, Iraq; Biotechnology Program, Department of Applied Science, Faculty of Mathematics and Natural Sciences, Universitas Negeri Malang, Indonesia; Department of Chemistry, Faculty of Mathematics and Natural Sciences, University of Udayana, Badung, Bali, Indonesia