(M1230-07-41) Investigation of the Dermal Delivery of Benzoyl Peroxide from Topically Applied Formulations In Vitro

Purpose: The purpose of the study was to evaluate the in vitro skin penetration of benzoyl peroxide and its metabolite benzoic acid from two formulations with different particle size distributions of the active: CUROXYL^® 42 (Vantage Specialty Chemicals) and Luperox. Human cadaver skin samples were used placed in Franz diffusion cells for the permeation studies. Topically applied benzoyl peroxide, once absorbed by the skin, was converted to benzoic acid in the skin layers and benzoic acid was detected in the receptor solution of the Franz diffusion cells. As a result, both Benzoyl Peroxide (BPO) and Benzoic Acid (BA) were quantified in skin layers and only BA in cell receptor samples using high-performance liquid chromatography (HPLC) techniques.

Methods: Permeation testing was performed using dermatomed human cadaver skin obtained from an accredited U.S. tissue bank (Science Care, Folcroft, PA,19032). Non-occluded vertical glass Franz diffusion cell (FDC) equipment was used with receptor volumes of 5 mls (Logan, NJ). Two formulations with different particle sizes of BPO (CUROXYL^® 42 and Luperox) were tested for the permeation of BPO and BA (n = 5 for each group). A sample of 500 µl of each formulation was applied to each donor compartment (0.64 cm²) of each Franz cell. During the skin permeation study, the skin temperature was maintained at 32˚C. Skin sample integrity was recorded using Trans Epidermal Water Loss (TEWL) measurements before and after the permeation study. At 8 hours, samples were taken of the receptor, and then after 12 hours, the receptor, epidermis, and dermis drug content were quantified using the previously validated HPLC assays for BPO and BA.

Results: The cumulative release of BA in CUROXYL^® 42 and Luperox after 12 hours was found to be 10.43±5.82µg/cm² and 1.63±0.78 µg/cm² respectively and for 8 hours was found to be 0.91±0.42 µg/cm² and 0 µg/cm² for CUROXYL 42  and Luperox respectively. The amount of BPO for CUROXYL^® 42 and Luperox in epidermis was found to be 24.39±6.92 (ug/mg) and 35.44±11.83. In dermis the values were 1.21±0.66(ug/mg) and 1.25±0.52 (ug/mg) respectively. The amount of BA for CUROXYL^® 42 and Luperox in epidermis was found to be 0.33±0.06(ug/mg) and 0.15±0.08 ug/mg). In dermis it was no BA was detected for either formulation.

Conclusion: Cumulative penetration amounts of benzoic acid BA from CUROXYL^® 42 at the end of 12 hours was significantly more than that from Luperox. The amount of BPO in the epidermis was significantly greater than dermis for both formulations. No benzoic acid (BA) was detected in the dermis for both formulations, but the epidermal layer had quantifiable levels of BA.

Schematic illustration of in vitro permeation study of BPO formulations

In vitro permeation study results