Comparative permeation studies of nondiluted and diluted betamethasone-17-valerate semisolid formulations through isolated human stratum corneum and artificial skin construct.
OBJECTIVE
This article deals with a comparative study of the permeation of the halogenated corticosteroid betamethasone-17-valerate (BM-17-V) through isolated human stratum corneum (SC) and artificial skin constructs (ASC) from different semisolid formulations described in the German Pharmacopoeia, i.e. wool fat alcohol ointment (WO), basis cream DAC (German Drug Code) and commercial products containing BM-17-V 0.1% weight such as Celestan-V cream, Celestan-V ointment, and Soderm ointment. In this study, pharmacopoeial ointment and cream were loaded in each case with BM-17-V.


METHODS
In vitropermeation experiments of BM-17-V were carried out in Franz diffusion cells using isolated human SC and ASC. Permeation data from both systems were compared statistically and those data were linearly correlated to each other. The saturation concentrations of BM-17-V within the formulations were calculated based on microscopical examination. The BM-17-V was metabolized via BM-21-V into betamethasone (BM) as its hydrolization product during the permeation experiments across SC. Since ASC has a higher enzymatic activity and less barrier qualities than SC, furthering the course of the permeation experiment, not only BM permeates besides the noncatabolized drug BM-17-V, but also 9alpha-fluoro-prednisolone as another decomposition product. The detection of BM-17-V and its degradation product was performed by high-performance liquid chromatography.


RESULTS
It was observed that the permeation of BM across ASC from all the formulations tested was higher by factors 9.7-27.7 than that from the same formulations permeating through SC, while the permeation sequence of the tested formulations was almost the same for SC and ASC. Afterwards the effect of the dilution of the semisolid formulations containing BM-17-V 0.1% weight on their permeation through SC was examined by mixing them with different ointments and a cream base. The permeation rate of BM from the dilution of Soderm ointment with WO and from WO diluted with different formulations from the German Pharmacopoeia were very similar.
Mitriaikina
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S
Institut fur Pharmazeutische Technologie, Technische Universitat Braunschweig, Braunschweig, Germany.
Muller-Goymann
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CC
D000287:Administration, Topical; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001624:Betamethasone Valerate / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002478:Cells, Cultured; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D066298:In Vitro Techniques; D009824:Ointments; D012869:Skin Absorption / Q000502:physiology*; D017768:Skin, Artificial
D000893:Anti-Inflammatory Agents; D009824:Ointments; D001624:Betamethasone Valerate