The wound healing effect of topical phenytoin has been reported but its effective delivery system is still underresearched. The present work aimed to formulate topical lipid-based gels for effective delivery of phenytoin. Three lipid-based emulsions with different droplet sizes were prepared using coconut kernel oil (CKO) and soybean oil (SBO) blends as an oil phase. Stable lipid-based emulsion with 100% emulsion stability index (ESI) over seven heating/cooling cycles could only be formed when the oil droplet satisfied the nano size criterion, as demonstrated by nano-emulsion. The stability of macro-emulsion and cream could be enhanced by the addition of Aristoflex ammonium acryloyldimethyl-taurate/VP (AVC) copolymer as the gelling agent. These gels, designated as nano-emulgel, macro-emulgel and cream-gel, were subsequently loaded with phenytoin. All gels exhibited non-Newtonian and shear-thinning flow behavior, with high yield stress ranged 18.8 -51.5 Pa. The in vitro drug release profiles of all formulations followed the first-order kinetic model, with R 2 > 0.95. It was found that lipid nano-emulgel demonstrated the highest release rate of phenytoin, with 93.12% drug released in 12 hours, followed by cream-gel with 56.42% and macro-emulgel with 51.51%. CKO/SBO nano-emulgel was identified as the most suitable lipid topical gel formulation for effective delivery of phenytoin.
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