Formulation and In Vitro Evaluation of Ethosomal Hydrogel as a Carrier System for Enhancing the Transdermal Delivery...

Puerarin (PUE) is categorized as a Class IV compound according to the Biopharmaceutics Classification System (BCS), characterized by both low solubility and poor permeability. Ethosomes, as transdermal drug delivery systems, can effectively penetrate the stratum corneum barrier and exhibit significantly higher transdermal flux. However, their application is hindered by inherent drawbacks, such as ethanol volatility and potential disruption of skin barrier integrity. To address these limitations and improve both loading and transdermal delivery efficiency of PUE, a PUE-loaded ethosomal hydrogel was developed by incorporating PUE-loaded ethosomes (PUE Es) into a hydrogel matrix. The optimized PUE Es formulation was achieved with a lecithin-to-drug ratio of 12.912:1, ethanol concentration of 37.107%, and hydration temperature of 33.073 °C, yielding a vesicle size of 160.03 ± 0.68 nm and encapsulation efficiency of 81.65 ± 1.55%. These ethosomes were subsequently incorporated into a Carbopol-based hydrogel to formulate the PUE ethosomal hydrogel, which exhibited favorable physicochemical characteristics and desirable rheological behavior. In vitro studies confirmed that the PUE ethosomal hydrogel significantly enhanced drug permeation and enabled sustained release of PUE compared with control formulations, and was well-fitted to the Weibull diffusion model. Collectively, these results indicate that the developed PUE ethosomal hydrogel holds considerable promise as a potential transdermal delivery system for PUE.