Details

Autor(en) / Beteiligte

• KOYAMA, Y
• BANDO, H
• YAMASHITA, F
• TAKAKURA, Y
• SEZAKI, H
• HASHIDA, M

Titel

Comparative analysis of percutaneous absorption enhancement by d-limonene and oleic acid based on a skin diffusion model

Ist Teil von

• Pharmaceutical research, 1994-03, Vol.11 (3), p.377-383

Ort / Verlag

New York, NY: Springer

Erscheinungsjahr

1994

Quelle

SpringerLINK Contemporary (Konsortium Baden-Württemberg)

Beschreibungen/Notizen

• Percutaneous absorption-enhancing effects of d-limonene and oleic acid were investigated using three model drugs with different lipophilicities in in vitro diffusion experiments with guinea pig skin. Pretreatment of the skin with d-limonene resulted in a large penetration enhancement for the lipophilic butylparaben (BP) and amphiphilic 6-mercaptopurine (6-MP) but had little effect on the hydrophilic mannitol (MT). Oleic acid caused a large effect only on 6-MP penetration. The penetration profiles were analyzed with a two-layer skin diffusion model consisting of stratum corneum with polar and nonpolar routes and viable epidermis plus dermis. Through curve-fitting, six parameters corresponding to drug diffusivity and partitioning in these three regions of the skin were obtained, and the mechanisms of enhancers were assessed in comparison with those of 1-geranylazacycloheptan-2-one (GACH) reported previously. Increased penetration was caused mainly by modification of the barrier property of the nonpolar route in the stratum corneum in all cases. In the nonpolar route, d-limonene increased mainly drug diffusivity, while GACH enhanced predominantly drug partitioning. On the other hand, oleic acid moderately increased both parameters.