<![CDATA[Background: Niacinamide is a widely used topical active ingredient, while the physical characteristics of gel formulations are strongly influenced by the type and proportion of gelling agents. The combination of Carbomer 940 and hydroxypropyl methylcellulose (HPMC) may provide complementary effects on viscosity, spreadability, and adhesiveness. However, the optimal proportion of these polymers in a 4% niacinamide gel has not been specifically established using a mixture-design approach. Methods: An experimental formulation study was conducted using a constrained mixture design with a total gelling-agent concentration of 2%. Carbomer 940 and HPMC were varied within the predetermined formulation constraints to generate eight experimental formulations. Each formulation was evaluated for organoleptic characteristics, homogeneity, pH, spreadability, adhesiveness, viscosity, and niacinamide content. The effects of polymer proportions were analyzed using Design-Expert software, and the optimum formulation was determined using a desirability approach. The optimum formulation was independently prepared for verification and subjected to a preliminary physical stability evaluation using three cycles of temperature cycling. Results: The optimum formulation consisted of 1.12% Carbomer 940 and 0.88% HPMC, with a desirability value of 0.98. Verification produced a pH of 5.75 ± 0.01, spreadability of 5.80 ± 0.02 cm, adhesiveness of 11.38 ± 0.08 s, viscosity of 10,017 ± 35 cP, and niacinamide content of 99.38 ± 0.08%. No significant differences were observed in the evaluated quantitative parameters after three temperature cycles (p > 0.05). Conclusion: The constrained mixture design identified 1.12% Carbomer 940 and 0.88% HPMC as the optimum proportion for the 4% niacinamide gel within the investigated formulation range. The optimum formulation showed balanced physical characteristics and no significant changes in the evaluated parameters after the preliminary temperature-cycling test. Further accelerated and long-term stability studies are required to confirm formulation stability.]]>
