Pharmaceuticals Solubility Modelling with a UNIversal QUAsiChemical Segment Based Activity Coefficient Model

A segmental contribution activity coefficient model, derived from the UNIversal QUAsichemical model, is proposed for fast, qualitative estimation of the solubility of organic nonelectrolytes in common solvents. Conceptually, the approach suggests that one account for the liquid nonidealityof mixtures of complex pharmaceutical molecules and small solvent molecules in terms of interactions between three pairwise interacting conceptual segments: hydrophobic segment, hydrophilic segment, and polar segment. In practice, these conceptual segments become themolecular descriptors used to represent the molecular surface characteristics of each solute and solvent molecule. The treatment results in component-specific molecular parameters as hydrophobicity (X), polarity (Y), and hydrophobicity (Z). Once the molecular parameters are determined using the experimental data for common solvents and solute molecules, the model offers a simple and practical thermodynamic framework to estimate solubility of complex pharmaceutical in solvents and to perform the other phase equilibrium calculations in support ofpharmaceutical process design.