Solubilization of monovalent weak electrolytes by micellization or complexation

In order to prepare a liquid formulation for a weak electrolyte, micellization or complexation is often applied with the solution pH controlled to have some of the drug molecules ionized. The efficiency of the micellization is evaluated by either the micellar solubilization capacities, κ_u, and κ_i or the micellar partition coefficients, K_u^m and K_i^m, for the unionized and ionized drug species. Similarly, the efficiency of complexation is evaluated by either the complex solubilization capacities, τ_u and τ_i or the drug-ligand binding constants, K_u^{1 : 1} and K_i^{1 : 1}. In this study, the experimental values of these descriptors were generated for seven ionizable drugs. The relationships of the logarithms of each descriptor to the logarithm of the octanol-water partition coefficient of the unionized drug (log P_u) and ionized drug species (log P_i) were evaluated. Although κ and τ cannot be predicted, this study shows that K^m and K^1:1 are dependent on log P for both the unionized and ionized drug species. Thus, the total drug solubility for a weak electrolyte solubilized by micellization or complexation can be predicted at any pH.