title: Analysis of in vitro skin permeation of 22-oxacalcitriol from ointments based on a two- or three-layer diffusion model considering diffusivity in a vehicle.
abstract: In the present study, in vitro rat skin permeation of 22-oxacalcitriol (OCT) from ointments having differing compositions was determined and discussed based on a diffusion model. Diffusion coefficients of OCT in two ointments, one containing 3% (w/w) medium chain triglyceride (MCT) (3MO) and the other 30% (w/w) MCT (30MO), were determined using a modified membraneless method resulting in values of 0.89x10(-4) and 1.87x10(-4) cm2/h, respectively. At 24 h after application with 3MO, 7% of the applied OCT dose permeated through full-thickness skin and 22% remained in the ointment, whereas with 30MO, 2% of the applied dose permeated through full-thickness skin and 65% remained in the ointment. The diffusion coefficient of OCT in 3MO was lower than 30MO but the cumulative amount of OCT permeated was higher. From analysis of skin permeation of OCT based on a diffusion model considering diffusivity in an ointment, the partition coefficient of OCT from the ointment to stratum corneum (K(SC/V)) was calculated to be five-fold higher with 3MO than with 30MO. Our simulation study based on a diffusion model suggests that the diffusion coefficients of OCT in both ointments were high enough to have no affect on the skin permeation of OCT in the present case and that the difference in the skin permeations of the ointments was mainly caused by a difference in K(SC/V).
authors.affiliation: Fuji Gotemba Research Laboratories, Chugai Pharmaceutical Co. Ltd., 1-135 Komakado, Gotemba, Shizuoka 412-8513, Japan. yamaguchikuj@chugai-pharm.co.jp
authors.forename: Koji
authors.initials: K
authors.lastname: Yamaguchi
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Mitsui
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Aso
authors.forename: Kenji
authors.initials: K
authors.lastname: Sugibayashi
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D003879:Dermatologic Agents / Q000493:pharmacokinetics*; D004058:Diffusion; D008297:Male; D008954:Models, Biological; D009823:Ointment Bases; D009824:Ointments; D010539:Permeability; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000378:metabolism; D012869:Skin Absorption; D014280:Triglycerides / Q000737:chemistry*
chemical_list: D003879:Dermatologic Agents; D009823:Ointment Bases; D009824:Ointments; D014280:Triglycerides; D002117:Calcitriol; C051883:maxacalcitol