Inter- and intralaboratory variation of in vitro diffusion cell measurements: An international multicenter study using quasi-standardized methods and materials

In vitro measurements of skin absorption are an increasingly important aspect of regulatory studies, product support claims, and formulation screening. However, such measurements are significantly affected by skin variability. The purpose of this study was to determine inter- and intralaboratory variation in diffusion cell measurements caused by factors other than skin. This was attained through the use of an artificial (silicone rubber) rate-limiting membrane and the provision of materials including a standard penetrant, methyl paraben (MP), and a minimally prescriptive protocol to each of the 18 participating laboratories. Standardized calculations of MP flux were determined from the data submitted by each laboratory by applying a predefined mathematical model. This was deemed necessary to eliminate any interlaboratory variation caused by different methods of flux calculations. Average fluxes of MP calculated and reported by each laboratory (60 +/- 27 mug cm(-2) h(-1), n = 25, range 27-101) were in agreement with the standardized calculations of MP flux (60 +/- 21 mug cm(-2) h(-1), range 19-120). The coefficient of variation between laboratories was approximately 35% and was manifest as a fourfold difference between the lowest and highest average flux values and a sixfold difference between the lowest and highest individual flux values. Intra-laboratory variation was lower, averaging 10% for five individuals using the same equipment within a single laboratory. Further studies should be performed to clarify the exact components responsible for nonskin-related variability in diffusion cell measurements. It is clear that further developments of in vitro methodologies for measuring skin absorption are required. (C) 2005 Wiley-Liss, Inc.

A note on the Balanced method

Recently the Balanced method was introduced as a class of quasi-implicit methods for solving stiff stochastic differential equations. We examine asymptotic and mean-square stability for several implementations of the Balanced method and give a generalized result for the mean-square stability region of any Balanced method. We also investigate the optimal implementation of the Balanced method with respect to strong convergence.

Development of a quasi-chemical viscosity model for fully liquid slags in the Al2O3-CaO-'FeO'-MgO-SiO2 system. Part 3. Summary of the model predictions for the Al2O3-CaO-MgO-SiO2 system and its sub-systems

A structurally-based quasi-chemical viscosity model for fully liquid slags in the Al2O3 CaO-'FeO'-MgOSiO2 system has been developed. The focus of the work described in the present paper is the analysis of the experimental data and viscosity models in the quaternary system Al2O3 CaO-MgO-SiO2 and its subsystems. A review of the experimental data, viscometry methods used and viscosity models available in the Al2O3 CaO-MgO-SiO2 and its sub-systems is reported. The quasi-chemical viscosity model is shown to provide good agreement between experimental data and predictions over the whole compositional range.