Development of Kamala-Based, a Thai Traditional Remedy, Nanoemulsion Gel and In Vitro Release Behavior of Phenylbutenoid Markers

Kamala is a traditional Thai herbal knee poultice containing phenylbutenoid compounds with potent anti-inflammatory activity; however, its conventional form is inconvenient to use and exhibits variability in active compound content. This study aimed to develop a Kamala-based nanoemulsion gel to enhance dermal delivery and improve formulation consistency. Oils, surfactants, and co-surfactants were screened for their solubilization efficiency of (E)-1-(3,4-dimethoxyphenyl)butadiene (DMPBD) and (E)-4-(3′,4′-dimethoxyphenyl)but-3-en-1-ol (Compound D) using GC–MS. Pseudo-ternary phase diagrams were constructed to identify isotropic regions, and nanoemulsions with different Smix ratios were prepared by ultrasonication. Droplet size, polydispersity index (PDI), and short-term stability were evaluated. The optimized nanoemulsion was incorporated into a gel, and in vitro release was assessed using Franz diffusion cells. Coconut oil exhibited the highest solubilization capacity for both markers. A Tween 80:n-butanol system (2:1) generated the largest isotropic region (22.88%). The optimized formulation (Kamala extract:coconut oil:Smix:water = 1:2:50:47) showed droplet sizes of 77.92 ± 8.34 nm at 0 h and 130.89 ± 29.16 nm at 72 h, with PDI < 0.20. The nanoemulsion gel prepared with Aristoflex Velvet® (1% w/w) was transparent and physically stable. Franz diffusion studies demonstrated enhanced cumulative release and flux of Compound D in PBS containing 1% Tween 80. These findings indicate that the Kamala nanoemulsion gel is a promising topical delivery system for phenylbutenoid compounds in knee osteoarthritis.