Development of Cosmetic Formulations Containing a Multicomponent
System with Ferulic Acid: Characterization and In Vitro Skin Release Tests
Ferulic Acid. Multicomponent System. Antioxidant Activity. Cosmetic Formulation. SPF. In Vitro Skin Release.
Phenolic compounds, such as ferulic acid (FA), are widely used in cosmetics due to their high
antioxidant activity and ability to protect against UV-induced damage, including skin
photoaging. However, their application is limited by low aqueous solubility and a tendency to
undergo rapid oxidation. To overcome these challenges, the multicomponent system
Cicloferulic® (CF) was developed, comprising FA, hydroxypropyl β-cyclodextrin
(HP-β-CD), and polyvinylpyrrolidone K30 (PVP K30). The system was characterized
physicochemically by DSC and TG/DTA, which demonstrated superior thermal stability of
CF compared to isolated FA. FTIR, SEM, and XRD analyses revealed molecular interactions
suggesting system formation and a transition from the crystalline to the amorphous state. In in
vitro cytotoxicity assays, FA exhibited toxicity at 5,000 µg/mL, whereas CF maintained cell
viability above 80% up to 10,000 µg/mL, showing toxicity only at 20,000 µg/mL. The FA
content incorporated into the system was quantified by UPLC, demonstrating high
incorporation efficiency and a yield of 92%. In antioxidant activity assays using a human
keratinocyte (HaCat) cell line, FA and CF showed similar activity at low concentrations, but
at higher concentrations, FA displayed pro-oxidant effects, whereas CF maintained high
antioxidant potential. In DPPH, ABTS, and CAT assays, CF exhibited greater antioxidant
activity than isolated FA; however, in cosmetic gel and emulsion formulations, efficacy was
reduced, possibly due to interactions between the complex and the aqueous vehicle. In in vitro
SPF assessments, formulations containing FA and CF initially showed higher values than
those with only sunscreen agents, but after 30 minutes of irradiation, a significant reduction in
SPF was observed, indicating no photostability effect. In in vitro cutaneous release studies,
formulations with isolated FA showed faster and higher release, while CF enabled slower and
controlled release, suggesting that complexation and formulation modulate FA availability
and flux. Cicloferulic® proved to be a promising strategy to overcome FA limitations,
offering enhanced stability, high antioxidant activity, and the potential for controlled and
sustained release of the active compound.