Objective: N-acetylcysteine is an antioxidant with thiol/sulfhydryl groups and is currently being developed as an active ingredient in anti-agingcreams. The study’s aim was to compare the stability and antioxidant activity of N-acetylcysteine in anti-aging creams formulated with and withouta transfersome carrier system.Methods: Stability was assessed by performing cycling, centrifugal, and accelerated stability tests. In addition, antioxidant activity was measuredby the DPPH method, and in vitro penetration was measured using Franz diffusion cells. The analysis of N-acetylcysteine was performed using highperformanceliquid chromatography with ultraviolet–visible detection at a wavelength of 214 nm and a flow rate of 1.0 mL/min, injection volume of5 μL, and a mobile phase of phosphate buffer pH 3.0.Results: The N-acetylcysteine transfersome and non-transfersome cream preparations did not change color or show phase separation during thecycling and centrifugal tests. The N-acetylcysteine in the transfersome and non-transfersome cream preparations had strong antioxidant activity,with half-maximal inhibitory concentrations of 26.90 μg/mL and 38.63 μg/mL, respectively. The in vitro penetration test using Franz diffusion cellsshowed that the cumulative amount of penetrated N-acetylcysteine was 7355.13 μg/cm2 (flux of 845.67 μg/cm2∙h) in the transfersome cream and4677.61 μg/cm2 (flux of 533.33 μg/cm2∙h) in the non-transfersome cream.Conclusion: The in vitro penetration test results showed that the transfersome formulations in creams were able to increase the cumulative amountand flux of penetrated N-acetylcysteine in anti-aging cream preparations relative to those not formulated with transfersome.
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