Ion-pair compounds of diacerein for enhancing skin permeability in vitro: the compatibility–permeability relationship of counter ion and diacerein

Figures & data

Figure 1. The FTIR spectra of (a) organic amine; (b) DCN and its ion-pair compounds.

Table 1. The chemical structure of DCN and counter ion.

Figure 2. Minimum energy of DCN ion-pair compounds forming with A (a) EA, (b) DEA, (c) TEA, (d) ETA, (e) DETA, and (f) TETA.

Table 2. Physicochemical properties of DCN and DCN ion-pair compounds.

	Melt point (°C)	Log P	Equilibrium solubility (μg/mL)
			IPM	PBS (pH 7.4)	Water
DCN	260.84	1.50 ± 0.01	83.59 ± 18.05	1441.87 ± 5.58	8.29 ± 0.27
DCN-ea	243.05	–0.39 ± 0.007	92.80 ± 14.10	12155.69 ± 81.21	6928.52 ± 4.80
DCN-Dea	176.57	–0.32 ± 0.007	410.37 ± 20.56	18473.86 ± 91.09	5453.36 ± 27.84
DCN-Tea	172.47	–0.27 ± 0.006	1385.02 ± 13.68	8187.55 ± 44.36	3232.52 ± 12.61
DCN-eta	148.83	–0.25 ± 0.005	121.56 ± 1.20	6099.91 ± 24.71	3059.63 ± 35.77
DCN-Deta	149.10	–0.22 ± 0.006	115.89 ± 16.60	11105.50 ± 18.51	3998.30 ± 12.50
DCN-Teta	153.92	–0.13 ± 0.005	99.38 ± 12.80	2514.24 ± 10.27	6374.94 ± 14.60

Table 3. Skin permeation data of DCN and its ion-pair compounds with different groups.

Samples	Q24h^a (µg/cm^2)	Jss^b (µg/cm^2⋅h^–1)	Tlag^c (h)
DCN	1.83 ± 0.22	0.06 ± 0.01	2.68 ± 0.78
DCN-ea	2.17 ± 0.30	0.08 ± 0.02	1.79 ± 0.66
DCN-Dea	2.82 ± 0.49	0.10 ± 0.01	4.12 ± 1.14
DCN-Tea	2.85 ± 0.64	0.11 ± 0.04	3.39 ± 0.55
DCN-eta	3.04 ± 0.67	0.09 ± 0.04	1.41 ± 0.56
DCN-Deta	4.03 ± 0.71	0.11 ± 0.02	2.16 ± 0.55
DCN-Teta	7.89 ± 0.38	0.17 ± 0.05	1.52 ± 0.48

^a Q_24h, the cumulative amount of drug permeated per unit area at 24 h.

^b J_ss, the steady-state flux obtained from the slope of the linear portion of the plots.

^c T_lag, the extrapolated value of the linear portion of the permeation curve to the abscissa.

Table 4. Skin permeation data of DCN and its ion-pair compounds with fatty amines.

Samples	Q24h^a (µg/cm^2)	Jss^b (µg/cm^2⋅h^–1)	Tlag^c (h)
DCN	1.83 ± 0.22	0.06 ± 0.01	2.68 ± 0.78
DCN-N6	3.86 ± 0.21	0.10 ± 0.02	1.52 ± 0.36
DCN-N8	4.30 ± 0.63	0.14 ± 0.03	2.15 ± 0.22
DCN-N10	6.41 ± 0.23	0.20 ± 0.03	1.38 ± 0.14
DCN-N12	11.28 ± 0.48	0.34 ± 0.02	2.50 ± 0.18
DCN-N14	7.03 ± 1.56	0.24 ± 0.05	1.31 ± 0.11
DCN-N16	6.44 ± 0.36	0.22 ± 0.01	1.28 ± 0.23
DCN-N18	5.97 ± 1.25	0.20 ± 0.01	1.42 ± 0.52

^a Q_24h, the cumulative amount of drug permeated per unit area at 24 h.

^b J_ss, the steady-state flux obtained from the slope of the linear portion of the plots.

^c T_lag, the extrapolated value of the linear portion of the permeation curve to the abscissa.

Figure 3. The binding energy distributions curves of DCN and (a) organic amines with different functional groups; (b) fatty amines; (c) triethanolamine and lauryl amine.