Contents of
This Chapter

• Concepts of solution, saturated and supersaturated

• Applications of solubility

• Methods of expressing solubility

• Factors affecting solubility

• Factors influencing solubility of solid in liquids

• Concepts of Raoult’s law

• Ideal and real solutions

• Positive and negative deviations from Raoult’s law

• Concepts of partially miscible liquids and critical
solution temperature

• Concept of phase rule and its applications

• Concepts of partially miscible liquids Phenol water
system, critical solution temperature and its applications

• Triethylamine- water system

• Nicotine- water system


• At the end of this lecture, student will be able to

  Define solubility,
saturated and unsaturated solution

  Discuss the
applications of solubility

  Describe the
methods to express solubility

  Describe the factor
Affecting Solubility

  Explain the
influence of solubility of solids in liquids

  Explain the
influence of solubility of liquids in liquids

  Explain the
influence of solubility of gases in liquids

  Describe the
concepts and applications of Raoult’s law

  Explain the
concepts, ideal and real solutions

– Describe the positive and negative deviations from
Raoult’s law

– Describe the principle and applications of partially
miscible liquids and critical solution temperature

– Explain phase rule and its applications

– Describe the principle and applications of partially
miscible liquids

  Describe the
concept of phenol water system and critical solution temperature

– Explain the applications of phenol- water system and
trietylamine-water system


• A solution can be defined as a homogenous mixture in which
one substance is said to dissolve in the other

• In quantitative terms, solubility is defined as the
concentration of solute in a saturated solution at a certain temperature

• Quantitatively, solubility is defined as a spontaneous
interaction of two or more substances to form a homogenous molecular dispersion

• Saturated solutions are the solution in which the
dissolved solute is in equilibrium with the solvent phase, at a definite

• An unsaturated solution is the solution containing the
dissolved solute in concentration below that is necessary for saturation, at a
definite temperature

• A supersaturated solution is the one that contains more of
the dissolved solute than that it would normally contain at a definite

• A supersaturated solution can be applied for
crystallisation process


• For the manufacture of liquid orals such as syrups and

• For the preparation of intravenous, intramuscular and
subcutaneous injections

• For the dissolution of drugs in GIT

• The release and absorption of a drug from an ointment or
an intramuscular injection

• It serves as a standard test for purity

• It provides information regarding intermolecular forces of

• Saturated solution theory is important for the
crystallization of drugs from solvents

• Principles of solubility are used for determining
physicochemical properties

• Differences in solubility in various solvents often serve
as a useful means of separating one component from the other and for
purification process

Descriptive phases in ml/g of

Approximate volume of solvent


Very soluble                                                                                         

less than 1

Freely soluble                                                                                      

from 1 to 10


from 10 to 30

Sparingly soluble                                                                                 

from 30 to 100

Slightly soluble                                                                                    

from 100 to 1000

Very slightly soluble                                                                            

from 1000 to 10000

Insoluble or practically insoluble                                                    

more than 10000

Methods of
Expression of Solubility

• The other methods of expressing solubility are:

– Weight per cent

– Volume per cent

– Normality – is a function of equivalents

Normality = (equivalents of X)/Liter

– Molarity – Number of moles of a solute dissolved/liter of

– Molality – Number of moles of solute dissolved/kilogram of

  Mole fraction – It
is equal to the moles of one component divided by the total moles in the
solution or mixture

  Mole per cent – all
the mole percents of a mixture add up to 100 mole percent. Mole percent can be
converted to mole fraction by dividing by 100.

– Equivalent weight

Influencing Solubility of Drugs

• Influence of particle size, shape and surface area

• Influence of physicochemical properties of drugs

• Influence of solvents

• Influence of pH of the medium

• Influence of co-solvents

• Influence of temperature

• Influence of other ingredients

• Influence of surfactants

that affect solubility

• The nature of the solute and solvent

• Temperature

• Pressure (only applicable to gases)

Nature of
Solute and Solvent

• Polar Solvent- a liquid made up of polar molecules

• Non-polar Solvent- a liquid made up of non-polar molecules

• When two substances are similar they can dissolve in each

– Polar solutes dissolve in polar solvents

– Non-polar solutes tend to dissolve in non-polar solvents

• “like dissolves like”

– Two liquids dissolve in each other because their molecules
are alike in polarity

• Ionic compounds are made up of charged ions similar to
polar compounds

• Ionic compounds are more soluble in a polar solvent than
in a non-polar solvent


Polar Solvent

Non-polar solvent











• Solutions of gases in liquids are affected by temperature

– As temperature increases, the solubility of a GAS in a
liquid decreases

• WHY?

– As temperature increases, the kinetic energy of the solute
gas increases and the gas can escape

• Solubility of SOLIDS in liquids: total opposite

– The solubility of a solid increases as the temperature
increases (there are a few exceptions)

• Temperatures Affecting the Solubility as the Solution is

– When the temperature drops while you mix the solute and
solvent, raising the temperature will increase solubility

– If the temperature stays neutral, the temperature will
have minimal or insignificant effect either way

– If the temperature is increased when the solute and
solvent are mixed, raising the temperature will decrease solubility


• When the pressure is increased over the SOLVENT, the
solubility of the gas is increased.

• Why?

– Pressure increases as gas molecules strike the surface to
enter solution is increased

• Henry’s Law:
Solubility of gas is directly proportional to the partial pressure of the gas
above the liquid


p= partial pressure

kh= gas constant


c= concentration of the solute


• Dissolving solutes happen in the surface area of the solvent

• Speed up the process by increasing the surface area

• The greater the surface area per unit mass, the quicker it
will dissolve


• Dissolving happens at the surface of the solvent

• Contact between the solvent and the solute is increased

Solubility of most liquids
is not greatly affected by temperature. Why?

The liquid-liquid intermolecular forces are not as strong as
the intermolecular forces between solid solute particles with the solvent.

of Gases in Liquid

Solubility of gas in liquid

α 1/T

– or –

As T of liquid ↑, solubility of gas ↓

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