Evaluation of in-vivo transdermal absorption of cyclosporin with absorption enhancer using intradermal microdialysis in rats.
The purpose of this study was to evaluate the effect of absorption enhancer on in-vivo transdermal absorption of cyclosporin using intradermal microdialysis in rats. Cyclosporin oily solutions (0.5, 2, 8% w/v) were prepared from Sandimmun (10% w/v oily oral preparation of cyclosporin) by diluting with olive oil. 1-[2-(Decylthio)ethyl] azacyclopentan-2-one (HPE-101) and glycerin were added to the cyclosporin formulation as an absorption enhancer at various concentrations between 1 and 20%. These formulations were applied to the shaved abdomen of rats treated with intradermal microdialysis at a flow rate of 2.5 microL min-1 for 6 h. Cyclosporin was immediately detected and attained a plateau in the dermal dialysate after topical application of cyclosporin oily solution alone. Cyclosporin levels in the dialysate increased with increasing cyclosporin concentrations in the formulation from 0.5 to 8% (w/v). HPE-101 did not influence cyclosporin absorption at concentrations less than 6% (w/v). Addition of 10% (w/v) HPE-101 significantly enhanced an apparent absorption rate of cyclosporin by 4.9 times. However, 20% (w/v) HPE-101 did not show the enhancing activity. On the other hand, addition of glycerin at concentrations of 6, 10, and 20% (v/v) significantly enhanced an apparent absorption rate of cyclosporin by 3.0, 6.4, and 6.9 times, respectively. The time lag for cyclosporin absorption was less than 0.21 h in all tested cases. This microdialysis study shows that glycerin is a suitable enhancer for improving the in-vivo cyclosporin absorption from the skin.
Nakashima
M
M
Department of Hospital Pharmacy, Nagasaki University School of Medicine, Japan.
Zhao
M F
MF
Ohya
H
H
Sakurai
M
M
Sasaki
H
H
Matsuyama
K
K
Ichikawa
M
M
D000279:Administration, Cutaneous; D000818:Animals; D016572:Cyclosporine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D017551:Microdialysis / Q000379:methods; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012869:Skin Absorption / Q000187:drug effects*
D004337:Drug Carriers; D007166:Immunosuppressive Agents; D011758:Pyrroles; D016572:Cyclosporine; C075725:1-(2-(decylthio)ethyl)azacyclopentane-2-one