Transdermal permeation modulation by cyclodextrins: a mechanistic study.
The purpose of this study was to investigate permeation modulation by beta- and 2-hydroxypropyl-beta-cyclodextrins (beta-CD and HP-beta-CD, respectively) alone and complexed with penetration enhancers for the test drugs 5-fluorouracil and estradiol through human skin, and to probe the value of the CDs in a barrier cream against toluene exposure. Methods include phase solubility studies, permeation experiments, and thermal analysis of stratum corneum; inclusion complexes were characterized by Karl Fischer titrimetry, infrared spectroscopy, and thermal analysis. Results show that complexes of terpenes or toluene with beta-CD were insoluble, whereas those with HP-beta-CD were soluble. The CDs did not enhance flux of either the polar or lipophilic drugs through skin; estradiol permeation was reduced following membrane pretreatment with either CD. Complexation of the lipophilic terpenes with the CDs reduced enhancer efficacy. When formulated into a barrier ointment both CDs, but particularly beta-CD, retarded toluene permeation through the skin and delayed the onset of maximum flux. It is concluded that the CDs themselves are not penetration enhancers for 5-fluorouracil or estradiol in human skin, and that they may be usefully incorporated into a barrier formulation to reduce percutaneous absorption of toxic materials on occupational exposure.
Williams
A C
AC
School of Pharmacy, University of Bradford, West Yorkshire, UK. A.C.Williams@bradford.ac.uk
Shatri
S R
SR
Barry
B W
BW
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000368:Aged; D003505:Cyclodextrins / Q000494:pharmacology*; D004817:Epidermis / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D012869:Skin Absorption / Q000187:drug effects*; D012995:Solubility; D014050:Toluene / Q000493:pharmacokinetics; D047392:beta-Cyclodextrins
D003505:Cyclodextrins; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D014050:Toluene; C031215:betadex