Abstract
Purpose: To study the in vitro penetration and in vivo pharmacokinetics of ferulic acid (FA), and the correlation between them after dermal administration.
 Methods: Franz diffusion cell was used to study in vitro penetration of FA. The concentration of FA in the Franz receiver solution was assessed by high performance liquid chromatography (HPLC). Prior to in vivo pharmacokinetics experiments, probe recovery was validated with respect to influencing factors such as flow rate, FA concentration, within-day stability and reproducibility of the probes. In in vivo pharmacokinetic experiment, six male CD-1 hairless mice were used. The micro-dialysis (MD) probe was implanted in the dermis of the rat skin, and dialysates from probe outlet were quantified directly by HPLC. In in vivo studies, deconvolution methods were used to determine the relationship between in vitro and in vivo data, and the correlation coefficient of linear equations.
 Results: There was significant effect of pH (5 ~ 8) on the penetration of FA. Increase in pH caused commensurate decrease in permeability. The Cmax of FA was 300.74 ± 31.86 ng/mL while Tmax was 138.00 ± 22.80 min after dermal administration of 1 mg/mL FA dissolved in phosphate buffered saline (PBS). The correlation coefficient (r) between in vitro and in vivo data was 0.9905.
 Conclusion: Both in vivo and in vitro experiments demonstrate that FA permeates the stratum corneum of skin rapidly. The unionized form of FA shows better penetration than the ionic form. In addition, results from correlation analysis indicate that the in vitro penetration characteristics of FA can be applied to predict its in vivo pharmacokinetics.
Highlights
Ferulic acid (FA) is one of the most abundant phenolic compounds in plants, especially Ligusticum wallichii, Angelica sinensis and Rhizoma cimicifugae, which are used extensively in Chinese Traditional Medicine [1]
These results indicate that the pH of the donor solution had a significant effect on FA
The experiment lasted for 6 h, because the FA concentration was below the LQD at 6 h, which corresponded to mean residence time (MRT) of 301.87 ± 64.50 min
Summary
Ferulic acid (FA) is one of the most abundant phenolic compounds in plants, especially Ligusticum wallichii, Angelica sinensis and Rhizoma cimicifugae, which are used extensively in Chinese Traditional Medicine [1]. Franz diffusion cell experiment and microdialysis (MD) technology were carried out to investigate the in vitro and in vivo penetration of FA. To learn more about the relationship between in vitro penetration and in vivo pharmacokinetics of FA, a correlation analysis between them was performed. Phosphate buffered saline (PBS) was prepared by mixing 0.04 mol/L of NaH2PO4 and aqueous solution of Na2HPO4, using NaCl to modify the osmotic pressure. Solutions of PBS of different pH were prepared by adding different amounts of aqueous 0.1% phosphoric acid, and adjusting their pH with FE20 pH meter [Mettler-Toledo Instruments (Shanghai) Co., Ltd, China]. Solutions for dermal application (1 mg/mL) were prepared by dissolving FA in PBS of different pH. The receiver solution used in in vitro study, and perfusate used in in vivo study were pure PBS. Water used in all experiments was passed through a Milli-Q water purification system
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