SOLUBILITY AND IN-VITRO TRANSDERMAL PERMEATION OF NIFEDIPINE

The solubilities of a hydrophobic drug, nifedipine, in a diverse panel of solvent and cosolvent systems were determined experimentally at ro om temperature. The observed solubilities were examined for deviations from regular solution solubilities as calculated by the Hildebrand an d Scott Equation. When presented graphically, the observed solubilitie s showed a pattern of positive deviations from ideality. The influence of solubilities in a cosolvent system on nifedipine permeation throug h hairless mouse skin was evaluated in the four binary cosolvent syste ms. The solubility of nifedipine was measured in four dimethyl isosorb ide (DMI)-based cosolvent mixtures and the theoretical skin:vehicle pa rtition coefficients were calculated. The amounts of nifedipine permea ted at 24 h post application from the representative donor systems adm inistered as suspensions were measured across hairless mouse skin in v itro. For the systems studied, it was concluded that: (1) nifedipine s olubility was enhanced in moderately polar cosolvent systems; (2) ther e was no correlation between the steady-state flux and drug solubility ; and (3) nifedipine permeation was higher from systems that contain s olvents known to readily pass rhs skin. (C) 1997 Elsevier Science B.V.