Formulate and evaluate microemulgel for skin pigmentation, containing a combination of Nigella sativa oil and Berberry extract. Nigella sativa oil is rich in thymoquinone, and berberry extract contains berberine. The solubility studies of nigella oil and berberry extract were conducted to select surfactants and cosurfactant. The pseudo ternary phase diagram was constructed based on the chosen oil and combination of surfactant and co-surfactant (Tween80 and propyleneglycol 400) at different ratios (1:1, 2:1, 3:1, 4:1, 5:1, 6:1). The microemulsion was assessed for globule size, zeta potential, pH value. The microemulsion was incorporated into a 1% carbopol 934 gel base and evaluated for spreadability, viscosity, drug release, drug content, and tyrosinase activity. The stability study of the optimized formulation was carried out as per ICH guidelines. A zero-order drug release mechanism was exhibited by microemulgel. The optimized microemulgel showed good stability for three months at accelerated conditions. The average globule size was 185.5 nm, the zeta potential was 0.4 mV, and drug permeation was 90.22% and 88.62% for berberine and thymoquinone, respectively, within 24 h. The tyrosinase activity results showed that a combination of berberry extract and Nigella sativa oil act as a tyrosinase accelerator. The optimized microemulgel formulation containing Nigella sativa oil and berberry extract is a stable and promising skin darkening agent.
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