SOLUBILITY & COMPLEXES

SOLUBILITY

● Maximum solute amount dissolving in solvent at specific temperature.

• Temperature (↑ solubility for endothermic dissolutions).

• Pressure (mostly for gases).

• Solvent polarity (“like dissolveslike”).

• Molecular structure and branching.

SOLUBILITY Influenced by

DISTRIBUTION LAW – NER NST

• Solute distributes between two immiscible solvents in a constant ratio at equilibrium. K = C1/C2

Extraction efficiency

- INCREASES with multiple small extractions rather than one large.

CONCEPTS DISTRIBUTION COEFFICIENT (K): -

solubility ratio between two immiscible solvents.

MISCIBILITY

- ability of liquids to mix.

POLARITY

polar solutes dissolve in polar solvents (e.g.water and alcohol are completely miscible).

SOLUBILITY AND STRUCTURE

• branching ↑ solubility

• longer nonpolar chains' ↓ solubility.

ENDOTHERMIC dissolution

• Solubility ↑ with temperature.

EXOTHERMIC dissolution

• Solubility ↓ with temperature

Very soluble

< 1

Freely soluble

1–10

Soluble

10–30

Sparingly soluble

30–100

Slightly soluble

100–1000

Very slightly soluble

1000–10

High

High

None

CLASS I

Solubility:

Permeability:

Limiting factor:

Low

High

Dissolution rate

CLASS II

Solubility:

Permeability:

Limiting factor:

High

Low

Permeation rate

CLASS III

Solubility:

Permeability:

Limiting factor:

Low

Low

Both

CLASS IV

Solubility:

Permeability:

Limiting factor:

COMPLEXES

• Formed by 

Lewis acid (metal ion) + 

Lewis base (ligand).

CHELATES

FORMED BY: multidentate ligands

• multiple donor atoms

Chelation

Enhances stability

• Can alter absorption.

EDTA

LEAD poisoning

• DOC

DEFERIPRONE

DESFERRIOXAMINE

IRON overload THALASSEMIA

• DOC

PENICILLAMINE

COPPER poisioning

• DOC

Cyclodextrins

monomolecular inclusion

• solubilize nonpolar drugs.

Clathrates

lattice entrapment

• e.g., warfarin sodium–isopropanol complex

Zeolites

molecular sieves for adsorption.

PHARMACEUTICAL RELEVANCE

of complexes

• Improves SOLUBILITY, STABILITY, TASTE MASKING.

• Can also cause drug–metal interactions (e.g., tetracyclines + iron → decreased absorption).

Albumin

• binding sites

Cu²⁺, Ni²⁺ bind at N-TERMINAL REGION.

Cu²⁺, Ni²⁺

Albumin binding sites: 

• —- bind at N-TERMINAL REGION.

N-TERMINAL REGION.

Albumin binding sites: 

• Cu²⁺, Ni²⁺ bind at