Background: Phenytoin is used commonly as an anticonvulsant agent with potential wound-healing properties. Objective: To formulate and characterize topical creams of phenytoin and investigate the wound-healing effect in the animal model. Methods: Three oil-in-water emulsion-based cream formulas were prepared using white soft paraffin, cetyl alcohol, lanolin, and olive oil blends as an oil phase. The stability was enhanced by the addition of cetostearyl alcohol, Tween 80, and methylparaben. After in vitro characterization, creams were loaded with phenytoin. Full-thickness wounds were created on rabbits that were divided into three groups (six animals each). The test group received 10% phenytoin creams, the positive control received a placebo, and the negative control received no treatment. The wound-healing activity of phenytoin was evaluated by the wound closure rate. Results: All formulations exhibited desirable physicochemical properties, including appearance, texture, and spreadability. The in vitro release results demonstrated that formula 3 sustained the phenytoin release profile, followed by 2 and 1, respectively. Based on physicochemical properties, pH values, and release profiles, formula 2 was selected for animal studies. The wound closure rate in animals treated with phenytoin was 10%, which was significantly higher than that of other groups. These results reveal that the phenytoin promotes faster wound closure and increased reepithelialization. Conclusions: Phenytoin 10% cream could be used as a safe and effective topical wound-healing agent.
