Vol. 7, Issue 2, Part G (2025)

Phenytoin, a widely used anticonvulsant with a narrow therapeutic index, exhibits poor aqueous solubility, variable bioavailability, and dose-dependent adverse effects, limiting its clinical efficacy. This study aimed to develop and characterize phenytoin-loaded nanosponges to enhance solubility, stability, and provide controlled drug release. Nanosponges were prepared using the solvent-emulsion diffusion method with ethyl cellulose as the polymer and polyvinyl alcohol (PVA) as the stabilizer. Preformulation studies confirmed the physicochemical suitability of phenytoin, with solubility being higher in ethanol, methanol, phosphate buffer pH 7.4, and PEG 400, and a partition coefficient of 2.47. UV Spectrophotometric analysis determined λ max at 205 nm, with a linear calibration curve obeying Beer’s law (R² = 0.9996). Drug-excipient compatibility studies via FT-IR revealed no chemical interactions. Nine nanosponge formulations were evaluated for drug content, entrapment efficiency, and in vitro release. Formulation F5, with a 1:4 drug-to-polymer ratio and 1.0% PVA, exhibited the highest drug content (96.05 ± 0.44%) and entrapment efficiency (87.60 ± 0.35%), along with a sustained release profile of 65.11% over 420 min, demonstrating reduced initial burst release. SEM and optical microscopy revealed spherical, porous nanosponges, while DLS and zeta potential analysis indicated a mean particle size of 332 nm and -32.38 mV, confirming colloidal stability. The study concludes that nanosponge encapsulation effectively enhances phenytoin solubility, stability, and controlled release, offering a promising approach to minimize dose-dependent toxicity, improve therapeutic consistency, and extend potential for alternative delivery routes, including topical or localized administration and thereby improving patient compliance and overall clinical outcomes.