Unexpected clobetasol propionate profile in human stratum corneum after topical application in vitro.
OBJECTIVE
The validity of using drug amount-depth profiles in stratum corneum to predict uptake of clobetasol propionate into stratum corneum and its transport into deeper skin layers was investigated.


METHODS
In vitro diffusion experiments through human epidermis were carried out using Franz-type glass diffusion cells. A saturated solution of clobetasol propionate in 20% (V/V) aqueous propylene glycol was topically applied for 48 h. Steady state flux was calculated from the cumulative amount of drug permeated vs. time profile. Epidermal partitioning was conducted by applying a saturated drug solution to both sides of the epidermis and allowing time to equilibrate. The tape stripping technique was used to define drug concentration-depth profiles in stratum corneum for both the diffusion and equilibrium experiments.


RESULTS
The concentration-depth profile of clobetasol propionate in stratum corneum for the diffusion experiment is biphasic. A logarithmic decline of the drug concentration over the first four to five tape strips flattens to a relatively constant low concentration level in deeper layers. The drug concentration-depth profile for the equilibrium studies displays a similar shape.


CONCLUSIONS
The shape of the concentration-depth profile of clobetasol propionate is mainly because of the variable partitioning coefficient in different stratum corneum layers.
Mueller
Beat
B
Department of Medicine, University of Queensland, Princess Alexandra Hospital, Woolloongabba, Australia.
Anissimov
Yuri G
YG
Roberts
Michael S
MS
D000287:Administration, Topical; D000328:Adult; D002990:Clobetasol / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D015194:Diffusion Chambers, Culture / Q000379:methods; D004817:Epidermis / Q000187:drug effects* / Q000378:metabolism*; D005260:Female; D006801:Humans; D008875:Middle Aged; D010539:Permeability
D002990:Clobetasol