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European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V (1)
Journal of controlled release : official journal of the Controlled Release Society (1)
Delgado-Charro, M. Begoña (2)
Carrupt, Pierre-Alain (1)
Guy, Richard H. (1)
Mudry, Blaise (1)
Russell, Lisa M. (1)
Wiedersberg, Sandra (1)
Year of Publication
The determination of stratum corneum thickness – an alternative approach
Russell, Lisa M.
European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V
The individual thickness of the stratum corneum is required to normalize drug permeation profiles in dermatopharmacokinetic studies. The thickness is often estimated using tape-striping combined with transepidermal water loss measurements. A linear transformation of Fick’s first law is used to relate the progressively thinner barrier with the corresponding increase in transepidermal water loss and to estimate the thickness by linear regression. However, the data from an important subset of subjects are poorly fitted to this linear model. This is typically due to the removal of loose outer layers of stratum corneum, which do not contribute significantly to barrier function. This work proposes two alternative non-linear models. All three models were used to fit data from 31 in vivo tape-striping experiments and their outcomes and goodness-of-fit compared. The results suggest that the linear model may overestimate the stratum corneum thickness and is open to subjectivity regarding the selection of data points to be fitted. The non-linear models satisfactorily fitted all the data, including all data points. No significant differences were found between the thicknesses derived from the two non-linear models. However, the analysis of the goodness-of-fit of the models to the data suggests a preference for a baseline-corrected approach.
Tape stripping; Transepidermal water loss (TEWL); stratum corneum; thickness; dermatopharmacokinetics
Quantitative structure-permeation relationship for iontophoretic transport across the skin
Guy, Richard H.
Journal of controlled release : official journal of the Controlled Release Society
The objective was to relate the efficiency of a charged drug to carry current across the skin during iontophoresis to its structural and/or physicochemical properties. The corollary was the establishment of a predictive relationship useful to predict the feasibility of iontophoretic drug delivery, and for the selection and optimization of drug candidates for this route of administration. A dataset of 16 cations, for which iontophoretic fluxes have been measured under identical conditions, with no competition from exogenous co-ions, was compiled. Maximum transport numbers correlated with ion mobilities and decreased with ionic size, the dependence indicating that the electromigration mechanism of iontophoresis would become negligible for drugs of hydrodynamic radius greater than about 8Å. Validation of the model was demonstrated by successfully predicting the transport numbers of three structurally distinct dipeptides, the iontophoretic data for which had been determined under distinctly different experimental conditions. Finally, for the “training” set of cations, a strong linear dependence between their transport numbers in skin and those in aqueous solution was demonstrated; the former were larger by approximately a factor of 1.4 consistent with skin’s cation permselectivity. In conclusion, this research offers a practical contribution to the development of a predictive structure-transport model of iontophoresis.
iontophoresis; skin; transport number; conductivity; structure-transport relationship
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