Sara Farahmand

Measuring transepidermal water loss: a comparative in vivo study of condenser‐chamber, unventilated‐chamber and open‐chamber systems

Background/aims: Two main systems have been utilized for measuring transepidermal water loss (TEWL): open chamber and closed chamber. Yet, further validation and standardization studies may be necessary to reveal the sensitivity, precision, and robustness of these instruments.

Transdermal drug pharmacokinetics in man: Interindividual variability and partial prediction

A database of human dermatopharmacokinetic parameters of 12 transdermal patches is established. The effect of system design, application site, and metabolism on pharmacokinetic data is discussed, and interindividual variability of data and its possible sources evaluated. Using multiple regression analysis, two equations based on drugs physicochemical characteristics are suggested for partial prediction of peak plasma concentration (C(max)) after patch application. Patch application presumably decreases variance as rub-off, wash and exfoliation steps are diminished. The results showed that interindividual variation, in terms of coefficient of variation (CV) of C(max), is inversely correlated with drugs molecular weight and lipophilicity in the range of 200<MW<400 and 1.6<logK(oct)<4.3. Multiple regression analysis of C(max) against physichochemical parameters demonstrated the prominent contribution of hydrogen bonding acceptability of the molecules on their maximal plasma concentration after patch administration. The findings suggest that the serum concentration profile for transdermal therapeutic systems (TTS) is a net result of the system performance, drug absorption and elimination. Thus, the variability in serum concentration is a function of variability of each process involved. This should be noted in explanation of effect of molecular features of drugs on their plasma concentration profile.

Estimating skin permeability from physicochemical characteristics of drugs: A comparison between conventional models and an in vivo-based approach

This study evaluates the correlation of some widely used skin permeability predictive models with a recently proposed empirical model based on human in vivo dermatopharmacokinetic data. Drug fluxes through the skin have been calculated using in vitro- and in vivo-based models, and observed in vivo data, and the values compared. Most in vitro-based models underestimate the in vivo data by 1-100-fold. The discrepancy between observed data and prediction reaches the maximum (1000-10,000-fold underestimation) for nicotine (with the smallest molecular weight and logK(oct)), nitroglycerin (with the largest number of hydrogen bond acceptor groups), and for oxybutynin (with the largest molecular weight and logK(oct)) where there was a 1000-fold flux overestimation. However, most models correlated well with the in vivo data and the in vivo-based model (p<0.05). The vehicle effect and using non-steady state in vivo data in the flux calculations partly account for the observed discrepancies between predicted and observed values. Nevertheless, these results reveal the need for further refinement of skin permeability predictive equations, using the steady state in vivo data, and consideration of formulation effect.

Cutaneous bioengineering instrumentation standardization: the Tissue Viability Imager

Background: Tissue Viability Imaging (TiVi) is a new bioengineering technology intended for remote two‐dimensional mapping of skin red blood cell concentration (RBCconc). Before use in the laboratory, work‐site and dermatology clinic, critical performance parameters of this emerging technology require careful evaluation.

Comparison of tissue viability imaging and colorimetry: skin blanching.

Background: Operator‐independent assessment of skin blanching is important in the development and evaluation of topically applied steroids. Spectroscopic instruments based on hand‐held probes, however, include elements of operator dependence such as difference in applied pressure and probe misalignment, while laser Doppler‐based methods are better suited for demonstration of skin vasodilatation than for vasoconstriction.

Tissue viability imaging: mapping skin erythema.

Background: Tissue Viability Imaging (TiVi) is an emerging bioengineering technology intended for two‐dimensional mapping of skin erythema and blanching. Before TiVi can be effectively used in studies of diseased or damaged skin, the variability in normal skin red blood cell concentration (RBCconc) requires evaluation.

Correlating percutaneous absorption with physicochemical parameters in vivo in man: agricultural, steroid, and other organic compounds

In vitro data are currently used to predict cutaneous chemical exposure based on physicochemical parameters. However, this in vitro data may not sufficiently account for what occurs in vivo. Previously, we modeled (via multivariate analysis) percutaneous absorption with physicochemical parameters using in vivo human transdermal patch‐based data. In our current study, we correlated absorption data from three human in vivo data sets to physicochemical parameters. Most univariate and multivariate analyses did not provide satisfactory fits, and only steroids demonstrated significant relationships, where: (1) total percentge absorption inversely correlated with molecular weight and number of hydrogen bond acceptor groups on the molecule; and (2) maximal absorption rate inversely correlated with molecular weight, and number of hydrogen bond donor and acceptor groups on the molecule. For the most part, however, disparities exist between our previous results with transdermal patches and our current results with acetone as the solvent. Reasons for this discordance may include: drug–vehicle interactions, compound variability and endpoint differences. With such variability between in vivo human data, current in vitro predictive models should be critically scrutinized. Copyright

Measuring human skin buffering capacity: an in vitro model

Background/purpose: It has been thought that skin possesses buffering capacity. This study measured the skin buffering capacity against two model solutions of acid and base at three concentrations with an in vitro system.