A study of the percutaneous absorption-enhancing effects of cyclodextrin derivatives in rats.
2-Hydroxypropyl-beta-cyclodextrin (HP-beta-CyD) and 2,6-dimethyl-beta-cyclodextrin (D-beta-CyD) were studied for transdermal penetration enhancement of the cytochrome P450 inhibitor liarozole by an in vivo transdermal absorption rat model. The mode of action of penetration enhancement was investigated by differential scanning calorimetry (DSC). In-vivo, HP-beta-CyD, as a 20% aqueous solution, increased the absorption of liarozole approximately threefold and a 20% aqueous solution of D-beta-CyD decreased the percutaneous absorption of liarozole in blood by a factor of 0.6. However, pretreatment with D-beta-CyD (20%, 4 h) enhanced the transdermal absorption 9.4-fold. In the DSC experiments the thermal profile of human stratum corneum was practically unchanged after treatment with HP-beta-CyD, but treatment with D-beta-CyD revealed an interaction of D-beta-CyD with the protein and lipid fraction. Thus the results from DSC and those from the permeability experiments revealed that D-beta-CyD acts as a transdermal absorption enhancer by changing the stratum corneum barrier whereas HP-beta-CyD influences the partitioning behaviour of the drug in the skin.
Vollmer
U
U
Janssen Research Foundation, Germany.
Müller
B W
BW
Peeters
J
J
Mesens
J
J
Wilffert
B
B
Peters
T
T
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000818:Animals; D002151:Calorimetry; D003505:Cyclodextrins / Q000494:pharmacology*; D065607:Cytochrome P-450 Enzyme Inhibitors; D006801:Humans; D007093:Imidazoles / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008954:Models, Biological; D009262:Nails / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012869:Skin Absorption / Q000187:drug effects* / Q000502:physiology; D013696:Temperature; D047392:beta-Cyclodextrins
D003505:Cyclodextrins; D065607:Cytochrome P-450 Enzyme Inhibitors; D007093:Imidazoles; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; C038119:heptakis(2,6-O-dimethyl)beta-cyclodextrin; C061121:liarozole