Tocopherols are well-known antioxidant and moisturizing agent. Tocopherol succinate (TS) are widely used in many skin products especially used in anti-aging and skin whitening product formulation. We previously reported the successful synthesis and preliminary characterizations of stable TS ethosomal gels (TSEG) (DOI: 10.1111/jocd.14907). Herein, we develop and further characterize TSEG to enhance the stability of the developed formulation with increased permeation through skin. Cold method technique was used to prepare TS ethosomes. The developed ethosomal vesicle size was 250 nm, which allowed TS to penetrate through the stratum corneum layer and act on melanocytes. For stability study was assessed by thermogravimetric analysis (TGA) by placing TSEG and unloaded/control ethosomal gel (CEG) at various temperature conditions, that is, 8°C, 25°C, 40°C, and 40°C ± 75% RH for 3 months. Organoleptic evaluation was done in terms of color, odor, and phase separation. Transmission electron microscopy (TEM), Fourier Transform infrared spectroscopy (FTIR), x-ray diffraction spectroscopy (XRD), zeta potential (ZP) and particle size (PS) was used for TSEG physical characterizations. Invitro dissolution and ex-vivo permeation studies (using Franz diffusion cell) were performed for both TSEG and CEG formulations. Human women (N = 34) were used to evaluate invivo biophysical parameters including erythema, melanin, moisture content, sebum level, and skin elasticity. Developed formulation was highly thermostable during the 3 months. Erythema, melanin, and sebum level decreased while marked improvement (p < 0.05) in moisture content and elasticity have been observed for the developed TSEG. The developed TSEG formulation was found to be efficient, safe (no adverse effects observed), stable (at least for 3 months), and easy to use for topical application with improved skin complexation and skin integrity.
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