Abstract
The effect of several pure or mixed solvent systems on the skin permeation of nicardipine hydrochloride (NC), a potential calcium antagonist, was examined. The effect was evaluated by measuring the steady-state permeation rate through the excised hairless rat skin mounted in a 2-chamber diffusion cell and by measuring the solubilities of NC in these solvents at 37 °C. Although the solubility of NC in propylene glycol (PG) was higher than those in water, ethanol (EtOH) and methylethylketone (MEK), the skin permeation rate of NC from PG suspension was as low as that from aqueous suspension and lower than those from EtOH and MEK suspensions. The solubilities of NC in a binary EtOH-water solvent system at various ratios were higher than those in the pure solvents. Such cosolvency was also observed in the ternary EtOH-MEK-water solvent system. The relationship between the logarithm of the calculated maximum flux of NC from the binary and ternary solvent systems and solvent composition was similar to that between the solubility of NC and the solvent composition. The highest permeability was observed from the solvent system which gave the highest solubility. These results suggest that the use of mixed solvents is effective as a vehicle for enhancing the skin permeation of NC.
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