Abstract: The present study was aimed at the development and evaluation of an Eplerenone liposomal drug delivery system using the thin-film hydration method to enhance drug encapsulation and achieve sustained drug release. Eplerenone liposomes were prepared by the thin-film hydration technique using phosphatidylcholine and cholesterol in different ratios. Eight formulations (F1–F8) were developed by varying the cholesterol concentration while maintaining a constant amount of phosphatidylcholine. The prepared liposomes were evaluated for particle size, zeta potential, surface morphology by scanning electron microscopy (SEM), drug entrapment efficiency, in vitro drug release using a Franz diffusion cell, drug release kinetics, and stability according to ICH guidelines. The prepared liposomes showed vesicle sizes ranging from 284 to 389 nm. SEM analysis confirmed the formation of spherical vesicles with smooth surfaces and minimal aggregation. Drug entrapment efficiency ranged from 86.98% to 95.68%, with formulation F4 exhibiting the highest entrapment efficiency (95.68%). The optimized formulation also demonstrated the highest cumulative drug release (98.35%) over 12 hours, indicating sustained release behavior. Stability studies performed under ICH storage conditions for three months showed no significant changes in drug release or physical characteristics, confirming good formulation stability. The study successfully developed a stable Eplerenone liposomal formulation with high drug entrapment efficiency, nanosized vesicles, and sustained drug release characteristics. The optimized formulation (F4) demonstrated superior physicochemical properties and controlled drug release, indicating that liposomal encapsulation is a promising approach for enhancing the delivery and therapeutic performance of Eplerenone.