Development of a reservoir-type transdermal delivery system containing eucalyptus oil for tetramethylpyrazine

Figures & data

Table 1.   Transdermal reservoir formulations of TMP containing different penetration enhancers.

(%, W/W)	1	2	3	4	5	6
TMP	15.6	15.6	15.6	15.6	15.6	15.6
Carbopol 934P	2.5	2.5	2.5	2.5	2.5	2.5
Ethanol	5.0	5.0	5.0	5.0	5.0	5.0
Eucalyptus oil				2.5	5.0	7.5
Azone			2.5
Menthol		2.5
Tween 80	2.0	2.0	2.0	2.0	2.0	2.0
Glycerin	10.0	10.0	10.0	10.0	10.0	10.0
Water added	100.0	100.0	100.0	100.0	100.0	100.0

Figure 1.  Mean ± SD amount of TMP permeated from the reservoir-type TDS containing different penetration enhancers across excised rat skin. The bars represent the SD (n = 3 or 4).

Table 2.   Permeation parameters of TMP in a reservoir-type TDS across excised rat skin or human epidermis containing different penetration enhancers.

Penetration enhancer	Jss (μg/cm^2/h)	ER	Tlag (h)	Q24 (mg/cm^2/24 h)
Control	121.5 ± 10.9	1.00	0.87 ± 0.18	2.8 ± 0.2
2.5% Menthol	237.1 ± 25.0*	1.95	2.45 ± 0.48	5.1 ± 0.5*
2.5% Azone	327.8 ± 13.6*	2.70	2.00 ± 0.73	7.2 ± 0.5*
2.5% Eucalyptus oil	410.6 ± 46.5*	3.38	1.65 ± 0.36	8.8 ± 0.9*
5.0% Eucalyptus oil	542.6 ± 49.7*	4.47	0.08 ± 0.07	13.1 ± 0.9*
7.5% Eucalyptus oil	563.5 ± 45.1*	4.64	0.00 ± 0.00	13.6 ± 1.8*
5.0% Eucalyptus oil  across human epidermis	346.0 ± 27.7	–	0.00 ± 0.00	7.9 ± 0.5

Each value is the mean ± SD of three or four determinations.

*Significantly different from the control group (p < 0.05).

Figure 2.  Mean ± SD amount of TMP permeated from the reservoir-type TDS containing 5% eucalyptus oil across excised human epidermis (n = 4).

Figure 3.  Mean ± SD plasma concentration of TMP following the oral administration of an immediate release tablet (108 mg) or the application of a TMP TDS patch (250 mg) in rabbits (n = 6).

Table 3.   Pharmacokinetic parameters of TMP following the oral administration of an immediate release tablet (dose 108 mg) or the application of a TMP transdermal delivery system (TDS) patch (250 mg).

	Oral tablet	Transdermal patch
Tmax (h)	0.50 ± 0.25	3.50 ± 1.52
Cmax (µg/mL)	3.88 ± 0.98	1.13 ± 0.28
MRT (h)	2.05 ± 0.65	10.02 ± 0.84
AUC0–t(µg/mL/h)	6.47 ± 1.83	15.93 ± 0.83
Css (µg/mL)	0.73 ± 0.12	0.66 ± 0.03
F (%)		106.29%

Each value is the mean ± SD (n = 6).