Investigation of drug partition property in artificial sebum

Targeted delivery of a therapeutic agent into the hair and sebaceous follicles greatly depends on the extent of drug partitioning/diffusion in the sebum. The objective of the present research was to develop a method to determine the sebum partition coefficient in order to facilitate the selection of sebum-targeted drug candidates. Partition coefficients of model drugs with different chemical structures and 4-hydroxybenzoate series compounds were measured in artificial sebum/water (Ksebum) and human stratum corneum/water (Ksc) at 37 °C. The relationship was evaluated between log Ksebum, log Ksc and clog P. The results of the partition coefficient studies indicate that the Ksebum of some drugs was significantly higher than the Ksc, whereas some drugs showed lower or similar Ksebum when compared with Ksc. Overall, a relatively poor correlation was observed between log Ksebum, log Ksc and clog P. However, a linear relationship exists between log Ksebum and clog P in the 4-hydroxybenzoate series compounds, indicating that Ksebum depends on the lipophilicity and chemical structure of the compounds. The results of the present study demonstrate that Ksebum is different from Ksc and calculated P and is likely to be a critical parameter reflecting drug delivery into hair and sebaceous follicles.