Design and Evaluation of Transdermal Patch with Pharmacological Screening and Anti-Anxiety Effect of Etifoxine

Anxiety disorders are prevalent psychiatric conditions often limited by the side effects and bioavailability issues of conventional oral anxiolytics. This study aimed to develop and evaluate Etifoxine-loaded transdermal patches as a non-invasive, sustained-release therapeutic alternative. Patches were prepared using a solvent casting method and optimized via a 3² factorial design varying polymer (HPMC:EC) and plasticizer (PEG 400) concentrations. The optimized formulation (Batch F2) exhibited uniform thickness (0.22±0.02 mm), adequate tensile strength (4.1±0.2 kg/cm²), high folding endurance (168±4), low moisture content (2.1±0.1%), suitable surface pH (6.5), and excellent drug content uniformity (97.3±0.6%). In-vitro release studies showed controlled drug release (88.2±1.4% at 8 h), while ex-vivo permeation across goat ear skin demonstrated efficient delivery (97.4±1.6% cumulative permeation at 24 h) with diffusion-controlled kinetics. In-silico docking revealed favourable binding of Etifoxine to the GABA-A receptor, and non-animal pharmacological screening using SH-SY5Y neuroblastoma cells confirmed concentration-dependent enhancement of GABAergic activity, with significant antioxidant effects observed in FRAP and DPPH assays, the optimized Etifoxine transdermal patch represents a promising, patient-friendly system for sustained anxiolytic therapy with potential neuroprotective benefits.