title: Investigation of drug partition property in artificial sebum.
abstract: 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 (K(sebum)) and human stratum corneum/water (K(sc)) at 37 degrees C. The relationship was evaluated between logK(sebum), logK(sc) and clogP. The results of the partition coefficient studies indicate that the K(sebum) of some drugs was significantly higher than the K(sc), whereas some drugs showed lower or similar K(sebum) when compared with K(sc). Overall, a relatively poor correlation was observed between logK(sebum), logK(sc) and clog P. However, a linear relationship exists between logK(sebum) and clog P in the 4-hydroxybenzoate series compounds, indicating that K(sebum) depends on the lipophilicity and chemical structure of the compounds. The results of the present study demonstrate that K(sebum) is different from K(sc) and calculated P and is likely to be a critical parameter reflecting drug delivery into hair and sebaceous follicles.
authors.affiliation: Research Formulations, Pfizer Global Research and Development, Ann Arbor, MI 48105, USA.
authors.forename: Satyanarayana
authors.initials: S
authors.lastname: Valiveti
authors.forename: James
authors.initials: J
authors.lastname: Wesley
authors.forename: Guang Wei
authors.initials: GW
authors.lastname: Lu
mesh_terms: D020003:1-Octanol / Q000737:chemistry; D002152:Calorimetry, Differential Scanning; D018859:Hair Follicle / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D004364:Pharmaceutical Preparations / Q000737:chemistry / Q000378:metabolism*; D012629:Sebum / Q000737:chemistry / Q000378:metabolism*; D012869:Skin Absorption; D014867:Water / Q000737:chemistry
chemical_list: D004364:Pharmaceutical Preparations; D014867:Water; D020003:1-Octanol