Penetration-enhancing effect of ethanol-water solvent system and ethanolic solution of carvone on transdermal permeability of nimodipine from HPMC gel across rat abdominal skin.

The aim of this investigation was to find the effect of the ethanol-water solvent system and the ethanolic solution of carvone on the permeation of nimodipine across rat abdominal skin in order to select a suitable solvent system and optimal concentration of carvone for the development of membrane-moderated transdermal therapeutic system of nimodipine. The solubility of nimodipine in water, ethanol, and ethanol-water cosolvent systems, or the selected concentration of carvone [2% (w/w) to 12% (w/w)] in 60:40 (v/v) ethanol-water were determined. The effect of these solvents or cosolvent systems on the transdermal permeation of nimodipine was also studied using in vitro permeability studies across the rat abdominal skin. The co-solvent system containing 60:40 (v/v) of ethanol-water showed highest permeability across the rat abdominal skin. Further, the effect of ethanolic solution [60% (v/v) ethanol-water] of carvone [2% (w/w) to 12% (w/w)] on the in vitro permeation of nimodipine across the rat abdominal skin from 2% (w/w) hydroxypropyl methylcellulose (HPMC) gel was also investigated. The transdermal permeability of nimodipine across rat abdominal skin was enhanced further by the addition of carvone to HPMC gel prepared with 60% (v/v) of ethanol. There was a steady effect on the flux of nimodipine (161.02 +/- 4.14 microg/cm2/hr) with an enhancement ratio of 4.56 when carvone was incorporated at a concentration of 10% (w/w) in HPMC gels prepared with 60% (v/v) ethanol. The Fourier transform infrared data indicated that ethanolic solution of carvone increased the transdermal permeability of nimodipine across the rat abdominal skin by partial extraction of lipids in the stratum corneum. The results suggest that 10% (w/w) of carvone in 60% (v/v) ethanol-water, along with HPMC as antinucleating agent may be useful for enhancing the skin permeability of nimodipine from the membrane-moderated transdermal therapeutic system.