Combination of penetration enhancers for transdermal drug delivery - Studies with imipramine hydrochloride

The objective of this investigation was to test the effectiveness of a novel combination strategy to increase transdermal permeation of imipramine hydrochloride (IMH, CAS 113-52-0) across rat skin and reduction of skin irritation caused by penetration enhancers. Ex vivo permeation parameters and skin damage in terms of total irritation score (TIS) were determined in presence of both menthol as well as oleic acid at 1, 2.5 and 5 % w/v and their combination at 2.5 % w/v in vehicle. While IMH flux increased from 150 to similar to700 mug. cm(-2) . h(-)1 with increase in menthol concentration from 1 to 5 % w/v, no significant difference (p > 0.05) in IMH flux was observed at the three concentrations studied with oleic acid. On the other hand, combination of menthol and oleic acid at 2.5 % achieved a flux that is comparable to those of individual enhancers at 5 % w/v in vehicle. Further, this combination caused less skin damage measured in terms of TIS. These results suggest that combination of penetration enhancers that belong to different chemical classes are useful to achieve a given permeation enhancement with low skin irritation potential.