Transdermal delivery of paeonol using cubic gel and microemulsion gel

Figures & data

Figure 1 Structure of paeonol.

Table 1 Compositions of various topical formulations for paeonol delivery

Components	Formulations
	A	B	C	D	E	F	Cubic gel	MG
Ethyl oleate						7
Isopropyl myristate	4	4	4	7	10			4
Crel:PEG400 = 1:1	28	39	50	28	28	28		28
Water	67	56	45	64	61	64	30	65
Carbomer 940								1
Triethanolamine								1
GMO							67
Paeonol	1	1	1	1	1	1	3	1

Abbreviations: Crel, Cremophor^® EL; PEG 400, polyethylene glycol; GMO, glyceryl monooleate; MG, microemulsion gel.

Figure 2 Pseudoternary phase diagrams of microemulsion composed of isopropyl myristate, surfactant (Crel), cosurfactant (PEG400) and water.

Note: Black area represents o/w microemulsion region; K_m = S/Cos.

Abbreviations: CEL, Cremophor EL^®, polyoxyethylated castor oil; Crel, Cremophor EL; IPM, isopropyl myristate; o/w, oil in water; PEG 400, polyethylene glycol.

Figure 3 Transmission electron microphotography of paeonol microemulsion.

Table 2 Permeability coefficient and enhancement ratio of paeonol through excised rat skin from different vehicles

Vehicle	Kp (cm/hour) × 10^−3	Enhancement ratio
Control	3.06 ± 0.10
A	6.53 ± 1.09*	2.13
MG	5.88 ± 0.28*	1.92
Cubic gel	8.34 ± 0.49**	2.73

* Notes: P < 0.05,

** P < 0.01, compared with control; each value represents means ± standard deviation of at least three experiments.

Abbreviation: MG, microemulsion gel.

Figure 4 The cumulative amount of paeonol from cubic gel (-●-) and microemulsion gel (-▴-) and control solution (-♦-).

Note: Results are expressed as means ± standard deviation of at least three experiments.

Table 3 Pharmacokinetic parameters obtained after oral and transdermal administration of paeonol in rats

Parameter	Transdermal administration		Oral administration
	Cubic gel	MG
Cmax (μg/mL)	0.68 ± 0.10*	0.72 ± 0.15*	1.64 ± 0.14
Tmax (hours)	3.00 ± 0.16**	2.00 ± 0.32**	0.25 ± 0.06
T1/2 (hours)	2.58 ± 0.13	3.45 ± 0.49**	1.54 ± 0.29
AUC (μg/mL/hour)	4.60 ± 0.54*	3.89 ± 1.01 (ns)	3.04 ± 0.42
MRT (hours)	5.63 ± 1.32*	5.62 ± 1.11*	1.64 ± 0.33

Notes: Data are expressed as the means ± standard deviation for six rats;

* P < 0.05, compared with oral administration;

** P < 0.01, compared with oral administration.

Abbreviations: AUC, area under the concentration–time curve; MG, microemulsion gel; C_max, maximum concentration; ns, not significant; T_max, time to reach maximum concentration; T_1/2, elimination half-life; MRT, mean residence time.

Figure 5 Plasma concentration of paeonol following oral and transdermal administration to rats.

Notes: Means ± standard deviation; n = 6; -▴-, oral administration; -●-, microemulsion gel transdermal administration; -■-, cubic gel transdermal administration.