ABSTRACT
This chapter provides a practical description of the physical phenomena leading to molecular-level solubilization or dispersion of solutes in a way that should enable the formulator to make informed decisions regarding formulation strategies for parenteral delivery. Solubility is discussed from the perspective of a thermodynamically defined equilibrium requiring several energetic steps in going from solute in a condensed phase to a solute in solution. Creation of alternative equilibria to “sequester” drug provides the basis for solubilization strategies, such as micellar partitioning, chemical ionization, complexation, and partitioning into emulsions. Drug molecules contain different structures and functional groups. The intraor intermolecular forces are dictated by intrinsic molecular properties, such as polarizability, electronic factors, topology and steric factors, lipophilicity, hydrogen bonding, surface areas, molar volumes and connectivity. Analog strategies are often focused on attempts to either decrease the lipophilicity or introduce hydrogen bonding groups which can enhance solvation in more hydrophilic media.
