US EPA

4929250 

Journal Article 

Rational vehicle design ensures targeted cutaneous steroid delivery 

Kircik, L; Okumu, F; Kandavilli, S; Sugarman, J 

2017 

1 

The Journal of Clinical and Aesthetic Dermatology
ISSN: 1941-2789 

10 

2 

12-19 

English 

28367258 

Objective: To design a topical vehicle that provided the optimal balance of betamethasone dipropionate penetration and retention in the skin, with minimal systemic absorption. Design: Six test formulations of betamethasone dipropionate 0.05% in vehicles contained the following penetration enhancers: elaidyl alcohol (Formulation-1), hexanol (Formulation-2), dodecanol (Formulation-3), octadecanol (Formulation-4), docosanol (Formulation-5), or oleyl alcohol (Formulation-6). Test agents were applied to human cadaver skin in static Franz-cell chambers containing receptor fluid. Measurements: Betamethasone absorption into the receptor fluid was measured over 24 hours. The distribution of betamethasone and its metabolites in the stratum corneum, epidermis, and dermis was analyzed using LC-MS/MS. The formulation with the optimal balance of penetration, permeation, retention, and minimal absorption was selected for a similar study comparing its penetration and absorption versus several commercially available betamethasone formulations. Results: Formulation-3 resulted in the highest retention of betamethasone in the skin as well as the highest steroid levels in the receptor fluid at 12 and 24 hours. Formulation-6 had the second highest retention of betamethasone in total skin, with relatively low absorption into the receptor fluid. All other variants had both lower steroid retention in the skin and lower absorption into the receptor fluid, with the exception of Formulation-2 which had higher absorption at 24 hours. Formulation-6/DFD-01 was selected for further development. Comparison of Formulation-6/DFD-01 with commercially available formulations of betamethasone dipropionate showed it had the highest steroid levels in the epidermis and dermis combined, with relatively low levels in the receptor fluid. Conclusion: Formulation-6/DFD-01 had the optimal balance of betamethasone retention in the skin, with low systemic absorption. This designed vehicle ensured retention of the corticosteroid in skin layers to maximize local efficacy while minimizing potential for hypothalamic-pituitary-adrenal suppression.