2. Introduction
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.
3. Stages
The process can be considered
in three stages:
● Removal of solute molecule
● Creation of cavity
● Insertion of solute
4. (i) A solute (drug) molecule is ‘removed’ from its
crystal.
● The solute must separate out from the bulk solute.
● This is enthalpically unfavourable as solute-solute interactions are
breaking but is entropically favourable.
5. Removal of solute molecule
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Drug crystal
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Drug crystal
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Drug molecule
6. (ii) A cavity for the drug molecule is created in the
solvent.
● 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.
8. (iii) The solute (drug) molecule is inserted into this
cavity.
● 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.
11. Polar solvent
● Polar solvents dissolve ionic solutes and other polar
substances.
● A difference in acidic and basic character of the constituents
in the Lewis electron donor–acceptor sense also contributes
to specific interactions in solutions.
● The solubility of a substance also depends on structural
features such as the ratio of the polar to the nonpolar groups
of the molecule.
● As the length of a nonpolar chain of an aliphatic alcohol
increases, the solubility of the compound in water decreases.
12. Hydrogen bonding
● The ability of the solute to
form hydrogen bonds is
significant than the polarity.
● Water dissolves phenols,
alcohols, aldehydes,
ketones, amines, and other
oxygen- and nitrogen
containing compounds that
can form hydrogen bonds
with water.
13. Nonpolar solvants
● Nonpolar compounds, however, can dissolve nonpolar
solutes with similar internal pressures through induced
dipole interactions.
● The solute molecules are kept in solution by the weak van
der Waals–London type of forces.
● Thus, oils and fats dissolve in carbon tetrachloride,
benzene, and mineraloil.
● Alkaloidal bases and fatty acids also dissolve in nonpolar
solvents.
14. Semipolar solvents
● Semipolar solvents, such as ketones and alcohols, can
induce a certain degree of polarity in nonpolar solvent
molecules, so that, for example, benzene, which is readily
polarizable, becomes soluble in alcohol.
● Semipolar compounds can act as intermediate solvents to
bring about miscibility of polar and nonpolar liquids.
15. ● 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.
