Background: Chemical exfoliation efficacy is significantly limited by pH-dependent permeability reduction above the pKa of glycolic acid (3.83), constraining consumer product development.
Objective: To develop and evaluate a biphasic serum utilizing temporary lecithin-glycolate ion-pairing to enhance stratum corneum permeation while maintaining safety at pH 3.9.
Methods: A biphasic formulation containing 10 wt% (weight percent) glycolic acid and 0.1 wt% lecithin was developed. Temporary ion-pairing was characterized by FT-IR spectroscopy. Ex vivo permeation and exfoliation were evaluated using porcine skin models. A 2-week double-blind, split-face clinical study (n = 37) assessed efficacy using instrumental probes (Visioscan, Corneofix, VISIA-CR, and ANTERA 3D) for exfoliation-related parameters and sensitive skin compatibility.
Results: FT-IR analysis confirmed lecithin-glycolate bonding via red-shifted C = O peaks, with spectral comparisons before and after shaking demonstrating the reversible nature of the change. The biphasic serum achieved 4.19-fold higher epidermal glycolic acid delivery compared to conventional formulations with minimal deep penetration. Clinical evaluation demonstrated superior exfoliation (45.52% improvement, p < 0.001), enhanced skin brightness, texture, and hydration. Redness and transepidermal water loss, assessed for sensitive skin suitability, showed significant improvements.
Conclusion: The biphasic system successfully overcomes pH-dependent limitations of glycolic acid through temporary ion-pairing, providing enhanced exfoliation efficacy with a superior safety profile for consumer applications.
Keywords: Stratum corneum permeation; biphasic formulation; chemical exfoliation; glycolic acid; ion‐pairing.
© 2026 The Author(s). Skin Research and Technology published by John Wiley & Sons Ltd.