AbstractContextAcacetin is reported as a potential drug candidate for the treatment of atrial fibrillation. However, clinical applications are limited by poor water solubility, limited ethanol solubility, and extremely low oral bioavailability.ObjectiveThe present study prepared and evaluated acacetin-loaded microemulsion (ME) to achieve efficient pharmacokinetics together with no or minimal invasiveness for transdermal delivery.Materials and methodsThe formulation of ME was determined by the water titration method based on solubility results. The optimized formulation was achieved by the simplex lattice experiment design. The optimized ME formulations FA, FB and FC (FA with 10% and 50% DMSO as enhancers, respectively) were evaluated byex vivopermeation with Franz diffusion cell and excised mice skin.In vivopharmacokinetic studies were also performed at 8 mg/kg in rats within 6 h by transdermal administration.ResultsThe optimal ME (FA) was comprised of 12.2% caprylic acid decanoate monoditriglyceride (MCF-NF), 39.8% Smix (RH40: Trans = 2:1 w/w) and 48% water, respectively. Acacetin-loaded FA with particle size 36.0 ± 3.6 nm and drug solubility 803.7 ± 32.1 mg/g was prepared. FB had significantly higher cumulative amounts and higher AUC0-∞(196.6 ± 11.0 min × μg/mL,p< 0.05) than that FA alone (121.4 ± 33.1 min × μg/mL).Discussion and conclusionsThe formulation of ME combined with the penetration enhancer can effectively improve the solubility and percutaneous absorption efficiency of acacetin, providing a new option for the non-invasive delivery of acacetin.