INVESTIGATIONS INTO THE PHARMACODYNAMIC EFFECTS OF DERMALLY ADMINISTERED MICROEMULSIONS CONTAINING BETA-BLOCKERS

Water uptake from the skin changes dermally applied near-saturated solutions of beta-blockers in microemulsion-bases into supersaturated microemulsions. Due to an enhanced thermodynamic activity, high absorption rates are expected from these preparations. The pharmacodynamic effect after dermal administration of such preparations has been evaluated using rabbits as a suitable in-vivo model. The dose dependency, influence of lipophilicity and of the thermodynamic activity of the drug is described. Assessment of dermal doses which were therapeutically equivalent to i.v. doses as, for example, shown with carazolol is possible. Although not all observed pharmacodynamic effects were due to these influences but rather due to the numerous other skin-vehicle-drug interactions which could not be explained with this model, the presented in-vitro model is helpful in evaluation of beta-blockers which were suitable candidates for transdermal administration.