Controlled In Vivo Release of Nicorandil from a Carvone-Based Transdermal Therapeutic System in Human Volunteers

Figures & data

FIG. 1 Mean (± S.D.) amount of nicorandil permeated from carvone-based HPMC gel drug reservoir across rat abdominal skin, EVA 2825 membrane, adhesive-coated EVA 2825, and adhesive-coated EVA 2825-rat skin composite (n=3).

TABLE 1 Mean (±S.D.) in vitro permeation parameters of nicorandil from carvone-based HPMC gel drug reservoir across rat abdominal skin, EVA 2825 membrane, adhesive-coated EVA 2825 membrane, and a composite of adhesive-coated EVA 2825 membrane and rat abdominal skin

Membrane/skin	J (μ g/cm^2 · h)	kp (cm/h × 10^3)^a	Amount (μ g/cm^2) of drug permeated at the end of 24 hr (Q24)
Rat abdominal skin (control)	365.6 ± 8.7	9.16 ± 0.23	8262.6 ± 264.4
EVA 2825	219.1 ± 6.2**	5.48 ± 0.15**	5182.8 ± 199.1**
Adhesive-coated EVA 2825	85.3 ± 3.9^a	4.63 ± 0.10^a	4402.0 ± 84.7^a
Adhesive-coated EVA 2825/ rat abdominal skin composite	151.8± 5.6^b	3.79 ± 0.1^b	3614.8 ± 135.6^b

*Mean of three experiments.

**Significant at p < 0.001 when compared with control.

^aSignificant at p < 0.001 when compared with EVA 2825.

^bSignificant at p < 0.001 when compared with adhesive-coated EVA 2825.

FIG. 2 Mean (± S.D.) plasma concentration of nicorandil following the oral administration of immediate release tablet (dose 5 mg) or application of carvone-based TTS (dose 80 mg) in human volunteers (n=6).

TABLE 2 Mean (±S.D.) pharmacokinetic parameters of nicorandil following oral administration of immediate-release tablet (5 mg) or dermal application of a carvone-based TTS (dose 80 mg) in human volunteers (n=6)

Pharmacokinetic parameter	Immediate-release tablet	Carvone-based TTS
Cmax (ng/ml)	89.0 ± 5.3	24.6 ± 0.7
Tmax (h)	0.6 ± 0.1	9.8 ± 0.4
AUC0-∞ (ng/ml·h)	260.4 ± 18.9	1025.9 ± 94.4
Relative bioavailability (%)	—	24.7 ± 2.3

*Significant at p<0.001 when compared with immediate-release tablet.