The application of anethole, menthone, and eugenol in transdermal penetration of valsartan: Enhancement and mechanistic investigation

Figures & data

Table 1. Some important physical parameters of investigated terpenes.

Terpenes	Structure	Molecular formula	Molecular weight (Da)	Type	Log P	Boiling point (°C)
Anethole		C10H12O	148.20	Monoterpene	3.39	234–237
Menthone		C10H18O	154.25	Monoterpene	2.63	207–210
Eugenol		C10H12O2	164.20	Monoterpene	2.30	254

Figure 1. Permeation profile of valsartan across rat skin in the absence and presence of various terpenes at (a) 1% w/v, (b) 3% w/v, and (c) 5% w/v in vehicle (mean ± SD).

Table 2. Effect of different terpenes on permeation of valsartan across rat skin (mean ± SD).

Terpenes (% w/v)	Flux (μg/cm^2/h) ±SD	Lag time (tL) (h) ± S.D	Kp × 10^−3 (cm/h) ±SD	ER ± SD
Control	39.3 ± 2.2	3.9 ± 0.6	7.9 ± 1.3	–
Anethole
1	174.3 ± 23.9	1.8 ± 0.2	34.9 ± 5.6	4.4 ± 1.7
3	155.4 ± 21.6	2.0 ± 0.2	31.1 ± 4.1	3.9 ± 1.6
5	141.9 ± 18.9	1.2 ± 0.2	28.4 ± 3.6	3.6 ± 1.1
Menthone
1	158.1 ± 23.7	0.56 ± 0.6	31.7 ± 3.1	4.0 ± 1.1
3	116.5 ± 11.3	1.2 ± 0.6	23.3 ± 2.3	2.9 ± 0.8
5	73.6 ± 11.0	4.2 ± 0.05	14.7 ± 2.1	1.8 ± 0.5
Eugenol
1	118.7 ± 39.3	0.6 ± 0.6	23.7 ± 4.1	3.0 ± 0.6
3	84.7 ± 28.2	1.7 ± 0.5	16.9 ± 3.5	2.1 ± 0.8
5	75.7 ± 25.5	2.8 ± 0.15	15.1 ± 1.3	1.9 ± 0.4

ER, enhancement ratio; Kp, permeability coefficient.

Figure 2. DSC thermograms of control skin and treated with 1% w/v terpenes for 24 h.

Figure 4. FTIR spectra of rat skin. Change in amide I (1640 cm⁻¹) and amide II (1550 cm⁻¹) vibrations after 24 h treatment with (a) control, (b) anethole, (c) menthone, and (d) eugenol.

Figure 3. FTIR spectra of rat skin. Change in lipid C–H stretching (2920 cm⁻¹) vibrations after 24 h treatment with (a) control, (b) anethole, (c) menthone, and (d) eugenol.

Table 3. Peak height of asymmetric CH and symmetric CH stretching absorbance before and after treatment of rat stratum corneum with control or 1% terpenes solutions for 24 h and their percentage decrease.

Treatment	Asymmetric CH stretching		Symmetric CH stretching
	Peak height	Decrease in peak height^a (%)	Peak height	Decrease in peak height^a (%)
	Control	0.391 ± 0.02	-	0.321 ± 0.01	-
Anethole	0.215 ± 0.01	45.0 ± 0.68	0.155 ± 0.001	51.7 ± 1.32
Menthone	0.242 ± 0.01	38.1 ± 0.45	0.177 ± 0.001	44.9 ± 0.79
Eugenol	0.293 ± 0.02	25.1 ± 0.32	0.225 ± 0.003	29.9 ± 0.46

^aPercentage decrease in peak height = [(peak height of control − peak height after treatment)/(peak height of control) *100].