Effect of thermodynamic activity on skin permeation and skin concentration of triamcinolone acetonide

Effects of thermodynamic activity and the state (solution/suspension) of triamcinolone acetonide (TA) on skin permeation and concentration were physicochemically and kinetically analyzed. Permeation of TA through a silicone membrane, hairless rat skin (full-thickness skin or stripped skin) or a three-dimensional cultured human skin model (LSE-high) was determined and a permeability coefficient (P), partition coefficient (K) , diffusion coefficient (D) and steady-state flux (J) were calculated. The resulting J values proportionally increased with an increase in the TA activity in the drug solution and similar P, K and D values were obtained independent of the TA state (solution/suspension) in all membranes except for full-thickness hairless rat skin. On the other hand, the TA permeation through full-thickness hairless rat skin with the 1000 microg/ml suspension was higher than that expected judging by the thermodynamic acidity of TA. Higher D and P values were also obtained in the skin permeation of TA from the 1000 microg/ml suspension. Morphological observation of the skin surface by scanning electron microscope (SEM) showed the presence of TA solids in the hair follicles after application of the TA suspension. These results suggest that dissolved TA may be permeated predominantly through the stratum corneum, but that solid TA may be passed through the hair follicles to enter the dermis. The present physicochemical and kinetic analysis provides useful information to develop topical steroid formulations.