Comparative Design, Development, and Multifaceted Evaluation of Hyaluronic Acid and Niacinamide Cosmetic Serum Formulations Using a Quality-by-Design Approach

ABSTRACT Background: Hyaluronic acid (HA) and niacinamide are validated cosmetic actives with distinct mechanisms, yet comprehensive comparisons of their optimized serum formulations are limited. Aims: To design, develop, and comparatively evaluate two serum formulations containing 1% HA (HA-S) and 5% niacinamide (N-S) using Quality-by-Design (QbD) principles. Methods: Pre-formulation screening used a 3×4 factorial design. Optimized formulations underwent physicochemical analysis, in vitro porcine skin permeation (Franz cells), hydration assessment via Corneometer® (n=12 human volunteers), sensory evaluation (n=20 trained panelists), accelerated stability (40°C/75% RH, 6 months), and Preservative Efficacy Testing (USP ). Results: Formulations showed target pH (5.8-6.0) but differed significantly in viscosity (HA-S: 200±15 cP; N-S: 75±10 cP; p