Solubility and Distribution

Phenomena
Solubility

 Concentration of a substance (solute) that dissolves in a given

volume of solution (solvent) at a certain temperature to form a
homogenous solution of the solute in the solvent

 Spontaneous interaction of two or more substances to form a

homogenous molecular dispersion
Saturated solution

 Is one in which the solute in solution is in equilibrium with the

solid phase
Unsaturated or Subsaturated solution

 Is one containing the dissolved solute in a concentration below that

necessary to complete saturation at a definite temperature
Supersaturated solution

 Is one that contains more of the dissolved solute than it would

normally contain at a definite temperature, were the undissolved
solute present
Solubility Definition in the United States Pharmacopeia
Description forms Parts of Solvent Required Solubility Range Solubility Assigned
(Solubility Definition) for One Part of Solute (mg/mL) (mg/mL)
Very soluble (VS) <1 >1,000 1,000
Freely soluble (FS) From 1 to 10 100—1,000 100
Soluble From 10 to 30 33—100 33
Sparingly soluble (SPS) From 30 to 100 10—33 10
Slightly soluble (SS) From 100 to 1,000 1—10 1
Very slightly soluble (VSS) From 1,000 to 10,000 0.1—1 0.1
Practically insoluble (PI) ≥10,000 <0.1 0.01
SOLVENT – SOLUTE INTERACTIONS
Polar solvents

 Dissolve ionic solutes and other polar substances

 Is a liquid with molecules that have a slight electrical charge due to

its shape

 Ex: water, most alcohols, formic acid, hydrogen fluoride, and

ammonia
Nonpolar solvents

 Are unable to reduce the attraction between the ions of strong and
weak electrolytes because of the solvents low dielectric constants.
Nor can the solvents break covalent bonds and ionize weak
electrolytes, because they belong to the group known an aprotic
solvents, and they cannot form hydrogen bridges with nonelectrolytes
 Ex: carbon tetrachloride (CCI4), benzene (C6H6), diethyl ether
(CH3CH2OCH2CH3), hexane (CH3(CH2)4CG3), methylene
chloride (CH2Cl2)
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 to bring about

miscibility of polar and nonpolar liquids
Polarity of Some Solvents and the Solutes that Readily Dissolve in Each Class of Solvent
Dielectric Constant of Solvent Solute
Solvent
(Approximately)
Decreasing 80 Water Inorganic salts, organic salts Decreasing
polarity Sugars, tannins water solubility
↓ 50 Glycols Castor oils, waxes ↓
30 Methyl and ethyl alcohols Resins, volatile oils, weak,
20 Aldehydes, ketones, and electrolytes including
higher alcohols, ethers, esters, barbiturates, alkaloids, and
and oxides phenols
Fixed oils, fats, petrolatum,
5 Hexanes, benzene, carbon paraffin, other hydrocarbons
tetrachloride, ethyl ether,
petroleum ether
Mineral oil and fixed
0 vegetables oils
SOLUBILITY OF LIQUIDS IN LIQUIDS

 Liquid-liquid systems can be divided into two categories according to solubility of the
substances in one another:

a) Complete miscibility polar and semipolar solvents mix in all proportions; Ex: water and
alcohol, glycerine and alcohol, acetone and alcohol
b) Partial miscibility a pair of liquid is considered partially miscible if there is a set of
compositions over which the liquids will form a two-phase liquid system. This is a common
situation where one is polar and the other non-polar (such as water and vegetable oils)

Miscibility  mutual solubilities of the components in liquid-liquid systems

SOLUBILITY OF SOLIDS IN LIQUIDS

 Systems of solids in liquids include the most frequently encountered and probably
the most important type of pharmaceutical solutions.
 Solubility is the interaction between particles of the solute and the solvent. Hence,
it depends on the nature of the solute and the solvent, as well as on the temperature
and pressure. But the solubility of solids in liquids is independent of pressure.
 Solubility of solids in liquids:
The solubility of solids in liquids depends upon two factors,
 Nature of the solute and solvent
 The temperature