Influence of cyclodextrin complexation on the in vitro permeation and skin metabolism of dexamethasone.
The influence of complexation of a model drug, dexamethasone acetate (DMA), with beta-cyclodextrin (beta-CyD) and hydroxypropyl-beta-cyclodextrin (HP-beta-CyD) on the in vitro permeation through hairless mouse skin and on skin metabolism have been investigated. Complexation with CyDs increased the amount of DMA permeated in the order of 2.0 and 3.0 times for beta-CyD and HP-beta-CyD, respectively. The partition coefficient, between stratum corneum and buffer (K(SC/buffer)), for DMA decreased when the drug was an inclusion complex, being greatest for DMA/HP-beta-CyD complex. Complexation protected the drug against skin metabolism. The increase of skin permeation and stability of the model drug in the skin suggest that the complexation with beta-CyD and HP-beta-CyD is a rational way to improve the physical-chemical properties of drugs for use in transdermal delivery systems.
Lopez
R F
RF
Faculty of Pharmaceutical Sciences at Ribeirão Preto, University of Sáo Paulo, Brazil.
Collett
J H
JH
Bentley
M V
MV
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002021:Buffers; D002851:Chromatography, High Pressure Liquid; D003505:Cyclodextrins; D003907:Dexamethasone / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005079:Excipients; D066298:In Vitro Techniques; D051379:Mice; D008812:Mice, Hairless; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption; D047392:beta-Cyclodextrins
D000893:Anti-Inflammatory Agents; D002021:Buffers; D003505:Cyclodextrins; D005079:Excipients; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D003907:Dexamethasone; C031215:betadex