Biopartitioning micellar chromatography to predict skin permeability

Abstract

Dermal absorption of chemicals is an area of increasing interest to the pharmaceutical and cosmetic industries, as well as in dermal exposure and risk assessment processes. In this paper the capability of biopartitioning micellar chromatography (BMC) as an in vitro technique to describe compound percutaneous absorption is evaluated. A multivariate study (principal component analysis, partial least squares) is performed in order to evaluate the importance of some physicochemical variables on the skin permeability constant values. From these results, a quantitative retention-activity relationship model for predicting the skin permeability constants that uses the BMC retention data and melting point as descriptor variables was obtained from a heterogeneous set of 43 compounds. The main advantage of the proposed methodology is that it allows the obtention of permeability constants of ionic compound and it can be very useful to predict the effect of pH of vehicle on the skin permeability of xenobiotics.

Linear combination methods for prediction and interpretation of drug skin permeation

“…For this reason, many in-vitro models, mimicking the composition and the structure of human stratum corneum, have been investigated so far in order to mathematically describe the process of skin permeation [7][8][9][10][11]. Likewise, different methods have been studied to analyse the raw data obtained in such experimental setups.…”

Avaliação do perfil de absorção da vivenina-2 e desenvolvimento de extrato seco padronizado de 'Lychnophora ericoides' com máxima extração deste flavonóide

“…First of all, a comparison between retention in BMC using standard, Kromasil C 18 (5 µm, 4.6 × 150 mm i.d.) (23,24), and capillary columns, Kromasil C 18 (5 µm, 0.5 × 150 mm i.d. ), was made in order to use the previously reported BMC-QRAR models obtained from retention data in a standard column.…”

“…Table 2 summarizes previously developed and validated QRAR models based on BMC retention in standard analytical columns to estimate passive transport of xenobiotics through different biological barriers: the gastrointestinal tract, blood-brain barrier, and skin (21)(22)(23)(24). From the BMC experimental retention data of polyphenolic compounds at different pH values in the capillary column (Table 3), their BMC retentions in a standard column were calculated using eq 4 and used to estimate the permeability profile of unaltered products ( Table 3).…”

“…In this field, our research group has proposed biopartitioning micellar chromatography (BMC), which uses C 18 stationary phases and polyoxyethylene (23) lauryl ether (Brij35) micellar mobile phases at near physiological conditions. The retention factor (k or log k) of drugs obtained in BMC has been successfully applied to construct QRAR models for describing and predicting the drug pharmacokinetic and pharmacodynamic properties of therapeutic families (18,19) and also to obtain general models to evaluate the xenobiotic permeability profile through different biological barriers such as the intestinal tract, skin, ocular tissue, and blood-brain barrier (20)(21)(22)(23)(24)(25). The success of BMC for these estimations can be attributed to similarities between the chromatographic system and biological barriers-extracellular fluid (19).…”

“…Martínez-Pla et al (23,24) developed a QRAR model based on BMC retention using a 0.04 mol L -1 Brij35 at pH 5.5 mobile phase to describe and predict skin permeability ( Table 2). In this model the retention of compounds in BMC expressed as log k BMC and melting point (MP), a physicochemical property strongly dependent on molecular weight and hydrogen bonding, was used as a predictive variable.…”