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

Abstract

Context

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.

Objective

The present study prepared and evaluated acacetin-loaded microemulsion (ME) to achieve efficient pharmacokinetics together with no or minimal invasiveness for transdermal delivery.

Materials and methods

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.

Results

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 < 0.05) than that FA alone (121.4 ± 33.1 min × μg/mL).

Discussion and conclusions

The 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.

Keywords:

• Emulsions
• solubility
• simplex lattice experiment design
• permeation enhancers
• pharmacokinetics

Acknowledgements

This study is in part financially supported by the National Natural Sciences Foundation of China (No. 82074016, No. 81603296); Program of Jiangsu Administration of Traditional Chinese Medicine (No. 2020ZX18).

Disclosure statement

The authors declare that they have no conflict of interest to disclose.