Development and Optimization of Candesartan Cilexitil-Loaded Ethosomal Gel for Enhanced Delivery: Improving Transdermal Therapeutics Via Box‒Behnken Statistical Design

Purpose: This research investigated the formulation and optimization of a candesartan cilexetil ethosomal gel, with an emphasis on improving patient adherence and medication delivery. This study investigated the transdermal administration of candesartan cilexetil using ethosomes as a colloidal carrier, which can assist in boosting its solubility, potentially increasing bioavailability and minimizing side effects. Methods: Propylene glycol was dissolved in the distilled water used as the aqueous phase, while the drug and soya lecithin dissolved in ethanol used as the organic phase. With a box-Behnken statistical design, the generated formulation was optimized for vesicle size, entrapment efficiency, and zeta potential as the dependent variables and soya lecithin amount and percentages of ethanol, and propylene glycol as the independent variables. A number of characteristics were used to characterize the optimal formulation. The ethosomal gel was created by incorporating an optimized formulation into the gel base. Parameters such as pH, viscosity, drug content, stability studies, in vitro release, ex vivo permeability, skin irritation, and histological investigations were used to characterize the ethosomal gel. Results: The optimized ethosomal dispersion via box-behnken statistical design showed vesicles size of 94.89 ± 1.21 nm, % entrapment efficiency (%EE) of 98.74 ± 1.33% and zeta potential of -15.08 ± 3.14 mV. The ex-vivo study confirmed the enhanced delivery of candesartan cilexitil from ethosomal gel than compare to free drug gel by virtue of better permeation and solubility. Histopathological studies demonstrated the safety of the candesartan cilexitil loaded ethosomal gel for transdermal administration without any allergic dermal reactions. Conclusion: The present study provides insightful insights into the development of improved transdermal drug delivery systems and highlights the significant potential of candesartan cilexetil ethosomal gel in therapeutic contexts.