Drugs, ionizable, solvation

These are only the theoretical dependencies real behavior of actual molecule usually is significantly altered due to different types of intermolecular interactions. Molecular solvation, association, hydrogen bonding, and counterions all have a significant effect on drug ionization constant and partitioning and distribution coefficients. Detailed and comprehensive discussion of these effects could be found in the book by Avdeef [22]. 

Substrate organization in membrane mimetic systems leads to altered solvation, ionization and reduction potentials and, hence, to altered reaction rates, paths and stereochemistries. These properties have been advantageously exploited, in turn, for reactivity control, catalysis, drug delivery and artificial photosynthesis (8). There are only limited examples of the utilization of membrane mimetic systems in permeability control. In order to gain insight into this important area, we have initiated a research program in BLMs. A status report of our activities in this area will be summarized in the next section. 

The extent of the ionization step depends on the relative strength of the conjugate acid-conjugate base pairs. The amphiprotic properties of the solvent have an essential effect on the equilibrium constant of this reaction step. The extent of the dissociation step is influenced by the polarity of the solvent, increasing with the dielectric constant of the solvent. In water, all products of acid-base reactions of moderate to low concentrations are essentially completely dissociated into solvated ions (Pecsok et al., 1976). The dissociation step is suppressed by addition or substitution with cosolvents of lower polarity, e.g., alcohols in aqueous formulations. The ion-pair aggregates may have absorption spectra different from the dissociated species. Thus, the amphiprotic properties and polarity (expressed as the dielectric constant) of the solvent are essential for the acid-base equilibrium of the drug and thus the absorption spectrum of the compound. This subject is further discussed in Section 14.2.3. 

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