Design and Characterization of Preservative Free Nepafenac Loaded Polyvinyl Alcohol Nanofiber for the Treatment of Dry Eye Syndrome

Dry eye syndrome (DES) is a chronic ocular disorder associated with tear film instability and inflammation. This study aimed to develop a preservative‐free nanofiber (NF)‐based ophthalmic formulation of nepafenac (NP) using polyvinyl alcohol (PVA) to address the limitations of conventional eye drops. NP‐loaded PVA nanofibers were prepared and optimized using a one‐variable‐at‐a‐time (OVAT) approach. The optimal formulation was obtained with 7% PVA, an applied voltage of 16 kV, and a flow rate of 0.2 μL/s, producing uniform, bead‐free nanofibers with an average diameter of 180 ± 1.45 nm and entrapment efficiency of 85% ± 2.13%. FTIR, DSC, and XRD confirmed no major drug–polymer interactions and indicated amorphization of NP within the nanofiber matrix. In vitro studies showed a 4.39‐fold increase in solubility and sustained release of ~79.87% over 6 h. Ex vivo corneal permeation improved significantly (38.15% ± 2.48%) compared with pure NP (14.26% ± 3.05%). The formulation also reduced inflammatory markers (IL‐1, IL‐6, COX‐2, NO; p < 0.01). Sterility and stability testing confirmed microbial safety and integrity for 6 months. Overall, the nanofiber system enhanced solubility, permeation, and therapeutic potential of NP for DES, warranting further long‐term evaluation.