Abstract

Tocotrienol-rich fraction (TRF) is a potent antioxidant capable of counteracting skin aging-related changes. However, TRF poses challenges for effective skin delivery. This study aimed to optimize the concentration of terpenes in a proniosomal gel (PNG) for TRF delivery and evaluate its physical properties, antioxidant activity, and topical release kinetics. The PNGs were prepared using the coacervation-phase separation technique. Various concentrations of d-limonene and squalene, as well as combinations of both, were tested to determine their effects on the formulation. The antioxidant activities of the sample were analyzed using 2,2-diphenyl-1-picrylhydrazyl radical scavenging assay and the in vitro release of TRF was studied through a Franz diffusion cell. All formulations displayed particle size ranging from 271.60 to 416.40 nm. The optimized PNG (M5), which is composed of 2.5% d-limonene and 2.5% squalene in the PNG, exhibited the highest entrapment efficiency (98.530% ± 0.048%) and antioxidant activity (2.951 ± 0.028 mg TE/g sample). A high flow point and shear-thinning flow characteristics were found by rheological characterization. Its predominant elastic nature in both amplitude and frequency sweeps demonstrated that the M5 rheological and stability characteristics were satisfactory. The release profile of M5 showed sustained and controlled TRF release by non-Fickian diffusion, while the control formulations showed an immediate release of TRF. The study successfully determined the optimal concentration of terpenes in the PNGs with the greatest physical and antioxidant properties while outperforming control samples for the TRF release.

Key words: Tocotrienol-rich fraction, Proniosomal gel, Niosomes, D-limonene, Squalene