Acacetin-loaded microemulsion for transdermal delivery: preparation, optimization and evaluation

• Published in: Pharmaceutical biology 2023-12, Vol.61 (1), p.790-798
• Main Authors: Wang, Yajing, Chen, Qian, Huang, Xianfeng, Yan, Xiaojing
• Format: Article
• Language: English
• Subjects: Administration, Cutaneous; Animals; Bioavailability; Biological Availability; Drug delivery; Drug development; Emulsions; Flavones; Invasiveness; Mice; Microemulsions; Octanoic acid; permeation enhancers; Pharmacokinetics; Rats; simplex lattice experiment design; Skin; Solubility; Titration; Water
• ISSN: 1388-0209; 1744-5116
• DOI: 10.1080/13880209.2023.2207597

Acacetin 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. The present study prepared and evaluated acacetin-loaded microemulsion (ME) to achieve efficient pharmacokinetics together with no or minimal invasiveness for transdermal delivery. The 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 by ex vivo permeation with Franz diffusion cell and excised mice skin. In vivo pharmacokinetic studies were also performed at 8 mg/kg in rats within 6 h by transdermal administration. The 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 AUC 0-∞ (196.6 ± 11.0 min × μg/mL, p