Objective: This research aims to establish an efficient methodology for selecting nanoemulsion components to synthesize eplerenone nanoemulsion for gel-based transdermal applications. Methods: The chemical compatibility study of eplerenone was investigated by FTIR, DSC, and solubility in oils, surfactants, and co-surfactants as the criteria for choice. We used visual appraisal and grading to assess the effectiveness of emulsification. Various excipients were tested depending on solubility. The final appearance, dispersibility, and ease of emulsification were used to visually assess the degree of self-emulsification of oil and emulsifier in a 1:3 mass ratio. Co-surfactants were assessed by mixing particular emulsifiers in a 2:1 (w/w) ratio with co-surfactants, and the oily component was added at a 1:3 (w/w) ratio to evaluate Smix's emulsification potential. A central composite design synthesized, evaluated, and optimized eplerenone nanoemulsions. Optimized nanoemulsions were characterized after a thermodynamic stability study for droplet size, ζ potential, viscosity, refractive index, pH measurements, and TEM. All the selected formulations were found to be stable, and the droplet size was found to be<110 nm. Results: Eplerenone was chemically compatible, and its maximum solubility was 171.3±0.92 and 169.3±2.22 in Kollicream®OA and Paceol, respectively. The evidence impressively found that Tween 20 and Kolliphor®EL were discovered as active emulsifiers, and Transcutol®P was revealed to be a co-surfactant. Outcomes showed that the emulsification efficacy of Kolliphor®EL (3% w/w) was able to emulsify Kollicream®OA (1% w/w), and Paceol failed. As well, Smix [Kolliphor®EL (2% w/w) and Transcutol®P (1% w/w)] were able to emulsify Kollicream®OA (1% w/w). Conclusion: The main conclusion from this work is the application of a visual appraisal and grading system to assess the final appearance, dispersibility, and ease of emulsification to eradicate the toxicity and irritation that nanoemulsions can cause. Optimised nanoemulsions can further formulate eplerenone's nanoemulsion gel for transdermal application.
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