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Effect of sebum and ointment rubbing was evaluated on the permeation of a model steroidal drug, triamcinolone acetonide (TA), from white petrolatum ointment through excised hairless rat skin. Two kinds of white petrolatum ointment containing TA at a concentration of 1.0% were made using a "pre-applied ointment," which was made by applying and recovering white petrolatum on and from the rat skin, respectively, and the "original ointment." Solubility and skin permeation of TA in and from both the ointments were measured and compared. TA solubility in the pre-applied ointment was about twice to that of the original ointment. Full-thickness skin and stripped skin permeabilities of TA from pre-applied ointment were about 2.3- and 1.5-times higher than those from the original ointment. In addition, the calculated partition coefficient of TA from pre-applied ointment to full-thickness skin was 2.7-times that of the original ointment. Next, the ointment-rubbing effect was determined. Skin permeation of TA from 1.0% TA original ointment with a 30 s-rubbing was 9-times higher than that after drug-free ointment-rubbing and application of 1.0% TA original ointment. The increase in solubility and skin permeation of TA due to pre-applied ointment is probably due to dissolution of TA by skin lipids extracted from the skin surface. Ointment rubbing increases the transient decrease in skin impedance and enhanced delivery of ointment base to the skin. These results are useful for development of ointment formulations and skin penetration mechanisms from an ointment base.

Effect of Sebum and Ointment Rubbing on the Skin Permeation of Triamcinolone Acetonide from White Petrolatum Ointment