Solubilization of monovalent weak electrolytes by micellization or complexation

Area of Science:

• Pharmaceutical Sciences
• Physical Chemistry
• Drug Delivery

Background:

• Liquid formulations for weak electrolytes often utilize micellization or complexation with controlled pH to enhance drug solubility.
• Key descriptors like micellar solubilization capacities (kappa) and complexation efficiencies (tau) are used to evaluate formulation performance.
• Understanding the relationship between these descriptors and drug properties is crucial for predicting solubility.

Purpose of the Study:

• To investigate the relationship between various micellization and complexation descriptors and the octanol-water partition coefficient (log P) of ionizable drugs.
• To determine if drug solubility in liquid formulations can be predicted based on these relationships.
• To evaluate experimental values for seven ionizable drugs.

Main Methods:

• Generated experimental values for micellar solubilization capacities (kappau, kappai), micellar partition coefficients (Kum, Kim), complex solubilization capacities (tauu, taui), and drug-ligand binding constants (Ku(1:1), Ki(1:1)).
• Evaluated the relationships between the logarithms of these descriptors and the logarithm of the octanol-water partition coefficient for unionized (log Pu) and ionized (log Pi) drug species.
• Focused on micellar partition coefficients (Km) and drug-ligand binding constants (K1:1) due to their dependence on log P.

Main Results:

• While kappa and tau values could not be directly predicted, Km and K1:1 were found to be dependent on log P for both unionized and ionized drug species.
• Established quantitative relationships between log P and the predictive descriptors (Km and K1:1).
• Demonstrated the utility of log P in predicting the efficiency of micellization and complexation.

Conclusions:

• The octanol-water partition coefficient (log P) is a significant factor influencing micellar partition coefficients (Km) and drug-ligand binding constants (K1:1).
• This dependency allows for the prediction of total drug solubility for weak electrolytes in liquid formulations across various pH conditions.
• The findings provide a valuable tool for optimizing liquid formulation development and predicting drug behavior.