Comparative Permeation Studies of Nondiluted and Diluted Betamethasone-17-Valerate Semisolid Formulations through Isolated Human Stratum Corneum and Artificial Skin Construct

Abstract

Purpose of the Study: 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 9α-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.

Model of in vitro Healing to Test the Influence of Dedifferentiated <i>Crithmum maritimum</i> Cells on Dermal Repair and Epidermal Regeneration

“…In addition, the free amino acids that constitute the 'natural moisturizing factor' involved in keeping the skin hydrated have their origin in the cleavage of profilaggrin into filaggrin [19,20] . However, our model does not allow studying skin permeability as described by Henning et al [21] , Mitriaikina et al [22] and Nicoli et al [23] , but testing activity and the tolerance of actives [24,25] .…”

Drug Release and Skin Penetration from Solid Lipid Nanoparticles and a Base Cream: A Systematic Approach from a Comparison of Three Glucocorticoids

“…To unravel the mechanism of SLN enhanced uptake in more detail, we studied the skin penetration of glucocorticoids (GCs): prednisolone 17-ethylcarbonate 21-propionate (prednicarbate, PC) and betamethasone 17-valerate (BMV) -which are frequently used in the treatment of inflammatory skin diseases [9,20] -as well as prednisolone (PD). The 3 GCs are close in molecular weight and molecular volume but vary in lipophilicity (octanol-water partition coefficient) and structure ( table 1 ).…”

State-of-the-art of 3D cultures (organs-on-a-chip) in safety testing and pathophysiology

“…this is often linked to the activation of a compound by biotransformation in keratinocytes and dendritic cells. Comprehensive investigations on the expression and functionality of enzymes involved in cutaneous biotransformation of xenobiotics in human skin ex vivo, RHe and RHS (Oesch et al, 2007;Harris et al, 2002;luu-the et al, 2009;Götz et al, 2012;Jäckh et al, 2012;Mitriaikina and Müller-Goymann, 2009;Bätz et al, 2013) are ongoing and the knowledge is currently improving. Biotransformation-competent RHe or RHS may be used for the study of penetration and biotransformation in a single step and RHe/RHS may be suitable to study genotoxicity and sensitization (Mehling et al, 2012) of compounds in the skin.…”