Effect of 2-hydroxypropyl-beta-cyclodextrin on percutaneous absorption of methyl paraben.
A potential use of 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CyD) to solubilize methyl paraben and to suppress its percutaneous absorption was examined, and compared with nonionic surfactant HCO-60. HP-beta-CyD significantly increased the solubility of methyl paraben in water, where the apparent 1:1 stability constant of the soluble complex was determined to be 2150 M-1. The in-vitro cutaneous permeability of methyl paraben through an isolated skin of hairless mouse was suppressed by HP-beta-CyD, thus promoting the bioconversion of methyl paraben to the less toxic metabolite, p-hydroxybenzoic acid (p-HBA) in the epidermis. These effects of HP-beta-CyD were greater than those of HCO-60. HP-beta-CyD (2% w/v) reduced the in-vivo percutaneous absorption of methyl paraben by 66% 24 h after the topical application of a solution containing [14C]methyl paraben to hairless mouse skin. Additionally, the percutaneous absorption of [14C]HP-beta-CyD was confirmed to be extremely low. These results suggest that HP-beta-CyD is useful in liquid preparations of methyl paraben for topical application.
Tanaka
M
M
Research Center, Shiseido Ltd, Yokohama, Japan.
Iwata
Y
Y
Kouzuki
Y
Y
Taniguchi
K
K
Matsuda
H
H
Arima
H
H
Tsuchiya
S
S
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000818:Animals; D003505:Cyclodextrins / Q000493:pharmacokinetics / Q000494:pharmacology*; D005260:Female; D051379:Mice; D008812:Mice, Hairless; D010226:Parabens / Q000493:pharmacokinetics*; D010539:Permeability; D012869:Skin Absorption / Q000187:drug effects*; D012995:Solubility; D047392:beta-Cyclodextrins
D003505:Cyclodextrins; D010226:Parabens; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; C015358:methylparaben