Enhanced skin permeation of 6-methoxy-2-naphthylacetic acid by salt formation

Figures & data

Figure 1. The chemical structure of the 6-MNA (1) and its salts (1a–1e).

Table 1. Physicochemical and spectral data of compounds (1, 1a–1e).

Compound	Physical state	Melting point (°C)	DSC (endotherm °C)	IR (cm^−1)
1	White solid	171–173	171.55	1693, 1416, 1265
1a	White solid	>275	281.12	1707, 1267, 1028
1b	Yellow solid	156–158	157.15	3285, 1704, 1263
1c	White solid	72–74	80.01/117.38	3385, 1706, 1387
1d	White solid	94–97	106.17	3354, 1709, 1227
1e	White solid	136–139	114.84	3389, 1707, 1264

Figure 2. FT-IR spectra of 6-MNA (1) and its salts (1a–1e) from 4000 to 400 cm⁻¹.

Figure 3. DSC thermograms of 6-MNA (1) and its salts (1a–1e) at a scanning rate of 5 K min⁻¹.

Figure 5. Aqueous solubility of 6-MNA (1) and salts (1a–1e) at pH 5.0 and pH 7.4.

Table 2. Aqueous solubility and partition coefficient (log P_app) values of 6-MNA (1) and its salts at pH 5.0 and at pH 7.4.

	Aqueous solubility (mM)		Log Papp
Compound	pH 5.0	pH 7.4	pH 5.0	pH 7.4
1	0.78 ± 0.18	63.34 ± 3.24	1.83 ± 0.18	0.23 ± 0.03
1a	17.01 ± 1.19	24.08 ± 2.27	0.80 ± 0.03	0.704 ± 0.06
1b	34.81 ± 2.24	27.13 ± 2.33	1.49 ± 0.14	1.063 ± 0.08
1c	36.02 ± 2.31	31.09 ± 2.41	0.91 ± 0.08	1.011 ± 0.06
1d	21.92 ± 1.42	25.40 ± 1.72	1.10 ± 0.12	1.061 ± 0.07
1e	08.10 ± 0.79	06.09 ± 0.39	2.31 ± 0.14	2.010 ± 0.11

Figure 6. Partition coefficient (log P_app) values of 6-MNA (1) and its salts (1a–1e).

Figure 7. Steady state flux (J_ss) of 6-MNA (1) and the salts (1a–1e) through excised human cadaver skin in vitro at 37 °C.

Table 3. Steady-state flux (J_ss) and permeability coefficients (K_p) of 6-MNA (1) and the salts (1a–1e) through excised human cadaver skin in vitro at 37 °C.

	Kp × 10^6 (cm/h)		Jss (n mol/cm^2h)
Compound	pH 5.0	pH 7.4	pH 5.0	pH 7.4
1	0.66 ± 0.02	0.02 ± 0.01	0.52 ± 0.06	1.42 ± 0.2
1a	0.13 ± 0.01	0.24 ± 0.02	2.15 ± 0.12	5.64 ± 0.3
1b	0.11 ± 0.01	0.49 ± 0.02	4.03 ± 0.03	13.45 ± 0.6
1c	0.08 ± 0.01	0.26 ± 0.01	3.13 ± 0.15	8.37 ± 0.3
1d	0.07 ± 0.01	0.23 ± 0.01	1.52 ± 0.10	5.89 ± 0.2
1e	0.16 ± 0.02	0.69 ± 0.03	1.29 ± 0.09	4.22 ± 0.3

p < 0.05 compared to 6-MNA (ANOVA).

Figure 8. Permeation profiles (mean ± SEM, n = 3–6) for 6-MNA (1) and its salts (1a–1e).