Enhancing effect of pyrrolidone derivatives on transdermal drug delivery II. Effect of application concentration and pre-treatment of enhancer

We compared the enhancing effects of 1-methyl- (I), 1-hexyl- (II) and 1-lauryl-2-pyrrolidone (III) on the penetration of phenolsulfonphthalein (Phenol red) as a model for a non-absorbable drug. Using the in vitro penetration technique and excised rat skin, the enhancers were applied at various concentrations. An increase in enhancer concentration was found to increase the flux and skin accumulation, and shorten the lag time for steady-state penetration of Phenol red. The enhancing effects of II and III ceased at 0.1 mmol/ml. Penetration for enhancers was found to increase with their own concentrations. Pre-treatment with enhancer for 5 h shortened the lag time for steady-state penetration of Phenol red. Removal of II from the donor side after pre-treatment decreased its enhancing effect. Enhancer III still showed an effect after removal.