MECHANISMS OF SOLUTE SOLVENT INTERACTIONS
A solute dissolves in a solvent when it forms favourable interactions with the solvent. This dissolving process all depends upon the free energy changes of both solute and solvent. The free energy of solvation is a combination of several factors. The process can be considered in three stages:
(i) A solute (drug) molecule is ‘removed’ from its crystal.
Removal of solute molecule
The solute must separate out from the bulk solute. This is enthalpically unfavourable as solute-solute interactions are breaking but is entropically favourable.
(ii) A cavity for the drug molecule is created in the solvent.
Creation of cavity
A cavity must be created in the solvent. The creation of the cavity will be entropically and enthalpically unfavourable as the ordered structure of the solvent decreases and there are fewer solvent-solvent interactions.
(iii) The solute (drug) molecule is inserted into this cavity.
Insertion of solute
The solute must occupy the cavity created in the solvent. Placing the solute molecule in the solvent cavity requires a number of solute–solvent contacts; the larger the solute molecule, the more contacts are created. If the surface area of the solute molecule is A, and the solute–solvent interface increases by γ12 A, where γ12 is the interfacial tension between the solvent1 and the solute2 then it leads to favourable solute-solvent interactions. This is entropically favourable as the mixture is more disordered than when the solute and solvent are not mixed.
Dissolution often occurs when the solute-solvent interactions are similar to the solvent-
solvent interactions, signified by the term ‘Like dissolves Like’. Hence, polar solutes dissolve in polar solvents, whereas non-polar solutes dissolve in non-polar solvents. Dissimilar nature of solute and solvent makes solute insoluble in the solvent. Substances dissolve when solvent-solute attraction is greater than solvent-solvent attraction and solute-solute attraction.
