Mixture-related factors, method development

The preceding discussion assumed a pure liquid was used for the measurement. Most molecules of interest, however, are not in the liquid state at room temperature. In this case it is common to dissolve the compound in an appropriate solvent and conduct the measurement. Contributions to the second harmonic signal are therefore obtained from both the solvent and solute. Since r and the local field factors that are related to e and n, (the dielectric constant and refractive index respectively) are concentration dependent, the determination of p for mixtures is not straightforward. Singer and Garito (15) have developed methods for obtaining r0, eQ, and nQ, the values of the above quantities at infinite dilution, from which accurate values for p can be obtained in most cases. 

Recently, Riviere and Brooks (2007) published a method to improve the prediction of dermal absorption of compounds dosed in complex chemical mixtures. The method predicts dermal absorption or penetration of topically applied compounds by developing quantitative structure-property relationship (QSPR) models based on linear free energy relations (LFERs). The QSPR equations are used to describe individual compound penetration based on the molecular descriptors for the compound, and these are modified by a mixture factor (MF), which accounts for the physical-chemical properties of the vehicle and mixture components. Principal components analysis is used to calculate the MF based on percentage composition of the vehicle and mixture components and physical-chemical properties. 

Not only solids, but many liquid systems also, have discontinuities in their properties over the factor space. Figure 10.1 shows a ternary mixture of water, an oil, and a surfactant. According to the proportions of the components, completely different phases are obtained and the methods of experimental design that we have seen so far, along with the polynomial or related models developed for then-analysis, are not suitable for analysis of the total system. For the experimental domain, it would be necessary to select a portion of the factor space with the same phase or phases over all of it. 

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