Thermochemical investigations of associated solutions: calculation of solute--solvent equilibrium constants from solubility measurements.
A simple solution model that has lead to successful predictive equations for the partial molar excess properties of a solute in simple binary solvent mixtures containing only nonspecific interactions is extended to include association between the solute and one of the solvent components. An expression is derived and tested for its ability to describe anthracene solubilities in binary solvent mixtures containing benzene. The best description of the experimental solubilities requires the formation of a 1:1 anthracene-benzene complex, with a molarity-based equilibrium constant of KcAC approximately equal to 0.107 M-1. In comparison, a stoichiometric complexation model which attributes all solubility enhancement to the formation of anthracene-benzene complexes requires a somewhat larger equilibrium constant (KcAC approximately equal to 0.228 M-1) to describe the solubility behavior of anthracene in the benzene-n-heptane system. The results of these calculations illustrate that the determination of solute-solvent equilibrium constants from solubility data depends on the theoretical model used and the manner in which nonspecific interactions are incorporated into the model.
Prediction of Physicochemical Properties Using a Semi-Empirical Group Contribution Approach
Considerable effort has been directed in the past toward understanding the relationship between molecular structure and the distribution-transport characteristics of chemicals and drugs. Although distribution is an equilibrium process and transport is a rate process, transport is subject to distribution for all passive diffusion processes and for most active transport phenomena in their presaturation phase. For example, a substantial portion of drug absorption involves partitioning into the rate-controlling membrane. The lipophilic-hydrophilic balance of ophthalmic drugs, for instance, largely determines their transcorneal absorption rate. Similarly, the rate of GI absorption of passively absorbed drugs usually depends on their ability to partition into the rate-determining barrier membrane. This condition is also true for dermal agents.
Solvency and hydrogen bonding interactions in nonaqueous systems.
Abstract A study of the importance of hydrogen-bonding interactions in the formation of complexes is useful in providing knowledge of the physical and chemical properties of drug molecules and hopefully it will eventually lead to rational formulation of drugs into suitable dosage forms. The present report deals with a study of some of the methods available for the experimental measurement of these interactions and the means of determining the association (equilibrium) constants from the experimental results. An attempt is made to develop suitable methods for the quantitative analysis of hydrogen-bonding data so that useful estimates of association constants can be made a priori. The effect of the non-aqueous solvent on the value of the association constant is also discussed and a method is given whereby an estimate of solvent interaction can be calculated.