Effects of co-application of betamethasone 17-valerate, from different formulations, with tacrolimus ointment on in vitro skin permeation

Abstract

Topical corticosteroids, such as betamethasone 17-valerate (BMV), are the primary therapy for atopic dermatitis. Tacrolimus is an alternative treatment and can potentially be used concomitantly with BMV on patients for atopic dermatitis. Studies have investigated pharmacological changes caused by these two drugs, but little is known about the penetration profile of these two drugs when used in combination. Objective: To examine the skin permeation and drug distribution of BMV, from foam or ointment vehicle, when co-applied with tacrolimus ointment. Methods: In vitro permeation through split-thickness human skin (∼0.25mm) was measured using flow-through diffusion cells. BMV 0.12% (foam and ointment) and tacrolimus ointment 0.1% were applied sequentially at a 5-minute interval (both orders of application were tested). Each drug was applied alone to serve as its own control. The formulations were tested on three to four replicate sections from each of three human donors. Receptor fluid was collected at 4-hour intervals. At 24 hours after application, the skin was washed and split into epidermis and dermis to measure drug content within these layers. The drug content in samples was measured by HPLC. Results: The co-application of BMV foam and tacrolimus ointment showed an increased permeation of BMV compared to BMV foam alone. The co-application of BMV ointment and tacrolimus ointment showed no improved permeation of BMV. These results held regardless of the order of application. The co-application of BMV foam and tacrolimus ointment also showed an increased amount of BMV in the dermis compared to the foam alone. However, there were no differences in the dermal content of BMV when BMV ointment was combined with tacrolimus ointment. Conclusions: These data indicate that co-application of BMV foam and tacrolimus ointment on the same skin site may result in enhanced permeation of BMV and may increase the amount of BMV in the dermis.