Quality by Design driven Development of Resveratrol Loaded Ethosomal hydrogel for Improved Dermatological Benefits via Enhanced Skin Permeation and Retention

Abstract Resveratrol is a potent anti oxidant agent and can be used for the effective management of different skin conditions like extrinsic skin ageing, psoriasis, etc. The objective of this research was to develop a dermal delivery system of resveratrol for its improved dermatological benefits for achieving its enhanced skin deposition profile with limited systemic exposure. Resveratrol loaded ethosomal hydrogel was developed and optimized using systematic Quality by Design approach. Firstly, the quality target product profile (QTPP) of ethosomal formulation was defined and critical quality attributes (CQAs) and critical material attributes (CMAs) were screened through risk assessment studies based on fish bone diagram. 32 full factorial design using Design Expert software was employed to optimize the selected CMAs. Concentration of phospholipid (X1) and concentration of ethanol (X2) were selected as independent CMAs. Vesicle size (Y1), entrapment efficiency (Y2), permeation flux (Y3) and drug deposition in dermal layer (Y4) were evaluated as dependant CQAs. Optimized formulation was then evaluated for physicochemical and skin permeation properties. Ethosomal hydrogel was able to significantly enhance the skin permeation parameters and skin deposition of resveratrol in comparison to the conventional cream. The results were highly ratified by CLSM studies in which ethosomal hydrogel was found to be vastly scattered in the deeper skin layers. Thus, there is evidence that systemically developed ethosomal gel can deliver enhanced amounts of bioactives into the skin and it is expected that a number of products for dermal/ transdermal applications will be developed in the future based on it.