Comparison of In Vitro and In Vivo Percutaneous Absorption Across Human Skin Using BAY1003803 Formulated as Ointment and Cream.

Direct comparisons between skin absorption data and clinical pharmacokinetic data are rare. Here we use the lipophilic nonsteroidal selective glucocorticoid receptor agonist BAY1003803 to make such a comparison. The objective is to find the extent to which measurements of skin permeation in vitro can be used to predict the corresponding permeation in vivo for human pharmacokinetics of topically applied substances. BAY1003803 was prepared in various formulations: ointment, hydrophilic cream, lipophilic cream, and milk. Its ability to permeate healthy human skin was measured in vitro in static diffusion cells, and percutaneous absorption as well as dermal delivery was measured thereafter, for 2 selected formulations, in vivo in healthy volunteers. Absorption in vivo comparing ointment and lipophilic cream was correlated with expectation based on the dermal delivery obtained in vitro. A 2.17-fold higher systemic exposure to BAY1003803 was achieved by the ointment formulation. This is well in line with the predicted exposure difference of 2.74 based on the in vitro data. In conclusion, in vitro skin absorption studies using human skin are suitable for the prediction of systemic exposure and formulation effects in vivo; they can therefore be applied to guide the design of clinical investigations of dermatological preparations.

Development of industrial catalysts for sustainable chlorine production.

The heterogeneously catalyzed gas-phase oxidation of HCl to Cl(2) offers an energy-efficient and eco- friendly route to recover chlorine from HCl-containing byproduct streams in the chemical industry. This process has attracted renewed interest in the last decade due to an increased chlorine demand and the growing excess of byproduct HCl from chlorination processes. Since its introduction (by Deacon in 1868) and till recent times, the industrialization of this reaction has been hindered by the lack of sufficiently active and durable materials. Recently, RuO(2)-based catalysts with outstanding activity and stability have been designed and they are being implemented for large-scale Cl(2) recycling. Herein, we review the main limiting features of traditional Cu-based catalysts and survey the key steps in the development of the new generation of industrial RuO(2)-based materials. As the expansion of this technology would benefit from cheaper, but comparably robust, alternatives to RuO(2)-based catalysts, a nov el CeO(2)-based catalyst which offers promising perspectives for application in this field has been introduced.

A delafossite-based copper catalyst for sustainable Cl2 production by HCl oxidation.

A copper catalyst based on a delafossite precursor (CuAlO(2)) displays high activity and extraordinary lifetime in the gas-phase oxidation of HCl to Cl(2), representing a cost-effective alternative to RuO(2)-based catalysts for chlorine recycling.

A QCAR-approach to materials modeling.

Little is known about the relationship between the function and structure of materials. Materials (solids with a function) are complex entities and a better knowledge of the parameters that contribute to function is desirable. Here, we present modeling approaches that correlate chemical composition with function of heterogeneous catalysts. The complete composition space of the mixed oxides of Ni-Cr-Mn and of Ni-Co-Mo-Mn (10% spacing) have been measured for the oxidation of propene to acroleine. The data have been collected, visualized and modeled. Different mathematical approaches such as Support Vector Machines, multilevel B-splines approximation and Kriging have been applied to model this relationship. High-throughput screening data of ternary and quaternary composition spreads are approximated to locate catalysts of high activity within the search space. For quaternary systems, slice plots offer a good tool for visualization of the results. Using these approximation techniques, the composition of the most active catalysts can be predicted. The study documents that distinct relationships between chemical composition and catalytic function exist and can be described by mathematical models.