Solubility and Free Energy of Solution

3 SOLUBILITY AND THERMODYNAMICS 11.3.1 Solubility and Free Energy of Solution 

The intrinsic aqueous solubility of a crystalline solute is measured at thermodynamic equilibrium between the undissolved crystalline form of the molecule and the neutral form of the molecule in solution, which can be written X If the activity 

FIGURE 11.1 Dlustration of two different thermodynamic cycles (top) crystal to gas phase to solution phase and (bottom) crystal to snpercooled liquid phase to solution phase. 

2 Computation of Solubility from the Thermodynamic Cycle of Solid to Supercooled Liquid to Aqueous Solution 

The thermodynamic cycle of sohd drug to supercooled hquid and then to aqueous solution has been the basis of several different methods to predict intrinsic aqueous solubihty. A supercooled liquid is a hypothetical state in which a pure solute that would normally be solid at the experimental temperature is considered to behave as a liquid. Although the supercooled liquid state is not accessible by experiments, it is 

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