) was measured and correlated with the physicochemical properties of the esters, including their solubility, viscosity, wettability, surface tension, and uptake. The amount of each model compound that permeated through the silicone membrane was not significantly correlated with the solubility of the esters but was significantly correlated with all other measured physical properties of the esters. Similar correlations were observed for the amounts of AMP, BA, and FP that passed through the Strat-M ® membrane. However, the amount of CF that permeated through the Strat-M ® membrane also correlated with the solubility of the esters. There was a highly significant correlation between the amount permeating through the silicone and Strat-M ® membranes because the model compounds had high lipophilicity. These findings demonstrated that to control the permeation of various chemicals through artificial membranes, it is important to consider the uptake of the esters and that the solubility of the esters is also an important consideration when using a more complex membrane.Key words alternative membrane; high-throughput; ester; silicone membrane; Strat-M; physical property In order to develop transdermal drug delivery systems, permeability has been evaluated using Fick's law of diffusion. 1,2)Fick's First Law indicates that the rate of mass transfer across a membrane is proportional to the concentration gradient expressed across the membrane. Synthetic artificial membranes are uniform and are designed to mimic human skin to avoid variability among tissues. They offer a simple and reproducible alternative to human and animal skins and provide key information to help understand the mechanisms of drug permeation by the evaluation of changes in a basic permeation parameter because, theoretically, skin permeation of chemicals can be expressed by physicochemical phenomena of diffusion and partition of compounds. Therefore, synthetic artificial membranes have been used in permeability evaluations. [3][4][5] Maitani et al.6) evaluated the permeability of diclofenac salts and free diclofenac acid through a silicone membrane to understand the mechanism of percutaneous absorption of ionizable drugs, and the existence of the lipid pathway for diclofenac salts was the same as for diclofenac acid. Strat-M ® is a commercially available multi-layered artificial membrane that is made from polyether sulfonic acid. 7) We reported previously also that the permeability coefficients, partition parameters, and diffusion parameters of chemicals through a Strat-M ® membrane were similar to those in human skin, and those in silicone membrane were under-or over-estimation to those in human skin, depending on the lipophilicity of the model compounds. 8,9) In addition, several previous studies have assessed the effects of vehicles on the permeation of chemicals through artificial membranes.10-13) For example, Twist and Zatz 10)evaluated the effect of alcohol on the permeation rate (flux) of methyl-, ethyl-, propyl-, and butyl-parabens. Dias et al. 12)r...

Although many in silico models were reported to predict the skin permeation of drugs from aqueous solutions, few studies were founded on the in silico estimation models for the skin permeation of drugs from neat oil formulations and o/w emulsions. In the present study, the cumulative amount of a model lipophilic drug, flurbiprofen (FP), that permeated through skin was determined from 12 different kinds of ester oils (Q oil) and an in silico model was developed for predicting the skin permeation of FP from these ester oils. Thus, the obtained Q oil values were well predicted with the FP solubility in the oils (S oil), the amount of FP uptake into the stratum corneum (SC oil) and molecular descriptors of dipolarity/polarizability (π 2 H) and molecular density. This model suggests that the thermodynamic activities of FP both in the formulations and skin are the key factors for predicting the skin permeation of FP from the ester oils. In addition, a high linear relationship was observed in the double-logarithm plots between the Q oil and the cumulative amount of FP permeated through skin from 20% ester oil in water emulsion (Q emul20%). Furthermore, the skin permeations of FP from 5 and 10% ester oil in water emulsions, Q emul5% and Q emul10% , respectively, were also predicted by the horizontal translation of the y-axis intercept of the liner equation for the relation between the Q oil and Q emul20%. These prediction methods must be helpful for designing topical oily and/or o/w emulsion formulations having suitable and high skin permeation rate of lipophilic drugs.