In general terms, which stability condition leads to higher solubility?

Choosing lower stability as the condition that leads to higher solubility is rooted in the fundamental principles of thermodynamics and solubility equilibria. When a substance, such as a drug, is less stable in its solid or undissolved form, it tends to favor a transition into a more soluble state.

This transition often involves overcoming a barrier, where the energy required for dissolution is less in scenarios of lower stability. In lower stability conditions, the intermolecular forces holding the particles together in the solid phase are weaker, making it easier for the substance to break apart and dissolve. As the substance goes into solution, it typically increases the overall entropy of the system, which is a thermodynamic driver for promoting solubility.

In contrast, higher stability often implies stronger interactions between molecules in the solid state, resulting in lower tendencies to dissolve. When a compound is highly stable, it possesses a lower propensity to enter the solution phase, thus exhibiting lower solubility.

Understanding this relationship between stability and solubility is crucial in pharmaceutical development, where enhancing the solubility of poorly soluble compounds can significantly improve their bioavailability and therapeutic effectiveness.