<![CDATA[The long-term use of topical non-steroidal anti-inflammatory drugs (NSAIDs) is associated with local irritation and disruption of the skin barrier, highlighting the need for safer plant-based alternatives with adequate formulation stability. Calotropis gigantea leaves contain flavonoids with reported anti-inflammatory activity; however, their topical performance is limited by poor solubility and instability. This study aimed to evaluate the effect of emulsifier balance on the physical stability and anti-inflammatory efficacy of a Calotropis gigantea leaf extract emulgel. Three emulgel formulations were prepared using different ratios of nonionic surfactants Tween 80 and Span 80 (2:8, 5:5, and 8:2) based on hydrophilic–lipophilic balance (HLB) principles. The formulations were evaluated for physicochemical characteristics, accelerated physical stability using a cycling test, and in vivo anti-inflammatory activity using a carrageenan-induced paw edema model in rats. The formulation containing a balanced emulsifier ratio (5:5) exhibited the smallest deviations in viscosity, spreadability, and pH after cycling tests and demonstrated the highest edema inhibition (68.98 ± 1.64%). These results indicate that emulsifier balance plays a critical role in maintaining emulgel stability and directly influences its biological performance. Although chemical stability and dermal safety were not evaluated, this study provides evidence that rational emulsifier selection is essential for improving the effectiveness of herbal topical formulations.]]>
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