Solubility
Contents of
This Chapter
• Concepts of solution, saturated and supersaturated
solution
• 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
Learning
Objectives
• 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
Solubility-
Definitions
• 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
temperature
• 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
temperature
• A supersaturated solution can be applied for
crystallisation process
Solubility-
Applications
• For the manufacture of liquid orals such as syrups and
elixirs
• 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
attraction
• 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 |
|
Soluble |
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
solution
– Molality – Number of moles of solute dissolved/kilogram of
solvent.
– 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
Factors
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
Factors
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
other
– 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
|
Solute |
Polar Solvent |
Non-polar solvent |
|
Polar |
Soluble |
Insoluble |
|
Non-Polar |
Insoluble |
Soluble |
|
Ionic |
Soluble |
Insoluble |
Temperature
• 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
Formed
– 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
Pressure
• 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=khc
p= partial pressure
kh= gas constant
p=khc
c= concentration of the solute
Surface
Area
• 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
Stirring
• 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.
Solubility
of Gases in Liquid
Solubility of gas in liquid
α 1/T
– or –
As T of liquid ↑, solubility of gas ↓
Solubility
of Gas and Pressure
As P of a gas above a liquid ↑, solubility of gas ↑
Solubility
Curves
Miscible
Liquids
• Liquids that are
miscible in all proportions are called as Miscible Liquids
• Example of miscible liquids- Ethyl alcohol in water
• This principle of solvents are applied on aerosol products
Raoult’s
Law
• The vapour pressure of liquid serves as a quantitative
expression for describing the escaping tendencies of molecules
• Raoult’s law states that “the partial vapour pressure of
each volatile constituents is equal to the vapour pressure of the pure
constituents multiplied by its mole fraction in the solution at a given
temperature”
• Raoult’s law may be mathematically expressed as
Partial vapour pressure= vapour pressure of pure liquid X
mole fraction of liquid
PA= PA0 XA………….(1)
PB= PB XB…………..(2)
• When two liquids are mixed, the vapour pressure of each
one is reduced by the presence of other by the extent of dilution of each phase
• Raoult’s law is appropriately suited to describe an ideal
solution
Ideal
Solutions
• Ideal solution is
defined as the
one in which
there is no change in the properties of the components
other than dilution, when they are mixed to form a solution
• Heat is neither absorbed nor evolved during mixing
• No shrinkage or expansion when liquids are mixed
• Examples of ideal solutions are – methanol-water, benzene-
toluene
• These liquids have similar properties, i.e., attractive
forces are in complete uniformity
Nonideal or
Real Solutions
• Most liquid mixtures show varying degree of deviation from
Raoult’s law, i.e. which does not obey Raoult’s law; these solutions are real
or non-ideal solutions
• When solute-solute, solute-solvent and solvent-solvent
interactions are unequal, these deviations are observed
• Typical examples are- carbon tetrachloride and
cyclohexane, chloroform and acetone
• Equations (1) and (2) may be modified as:
PA= PA0αA…………(3)
PB= PB0αB………..(4)
• αA and αB indicates are activities of components A and B respectively
Deviation from
Raoult’s Law- Positive Deviation
• In some liquid systems, the vapour pressure is greater
than the sum of the partial pressures of the individual components
• Such systems exhibit positive deviation from Raoult’s law
• Examples are carbon tetrachloride and cyclohexane, water
and ethanol etc.
• This type of behaviour occurs when the components differ
in their polarity, length of hydrocarbon chain and degree of association
Deviation from
Raoult’s Law- Negative Deviation
• In some liquid systems, the vapour pressure is less than
the sum of partial pressures of the individual components
• Such systems are said to exhibit negative deviation from
Raoult’s law
• Examples include chloroform and acetone, pyridine and
acetic acid etc.
• This type of behaviour occurs when interactions such as
hydrogen bonding, salt formation and hydration occur between the components
Phase Rule
• Phase is defined as a homogenous physically distinct
portion of a system that is separated by bounding surfaces from each other
• Phase rule is a device for relating the effect of the
least number of independent variables upon the various phases that can exist in
equilibrium system containing a given number of components
• Examples of independent variables are temperature,
pressure and concentration
Phase Rule
and Its Applications
• It is known as Gibb’s phase rule, and may be stated
mathematically as:
F = C – P + 2……..(1)
Where, F= number of degree of freedom
C= number of components
P= number of phases
• Applications of phase rule are:
– In determining the purity of a substance
– In the solubility phenomenon
Partially
Miscible Liquids
• Partially miscible liquids or conjugate liquids are
defined as a two phase liquid system in which their mutual solubility in one
another is limited
• As such when temperature is increased, the mutual
solubility of one liquid in another increases
• Miscibility temperature is defined as the temperature at
which two conjugate solutions are mutually soluble
• The miscibility temperature is identified either by the disappearance
of turbidity or by reappearance of turbidity
• When solubility of one liquid in another liquid is plotted
against miscibility temperature, a specific pattern is obtained
• These solubility temperature profiles are known as
miscibility curves or phase diagrams
• Applications of phase diagrams are:
– To decide the proportion of two liquids to be taken during
formulation of solutions
– Testing purity of a liquid
• Typical examples of partially miscible liquids are:
– Phenol-water system
– Trimethylamine-water system
– Nicotine – water system
Phenol- Water
System
• The miscibility pattern of phenol-water system can be
shown as below:
• The left hand side of the curve represents the % W/W of phenol
in water at various temperature
• The right hand side of the curve represents % W/W of water
in phenol at various temperature
• The two curves meet at a maximum temperature of 66.80C
• The critical solution temperature (CST) is defined as
maximum temperature at which the two conjugate solutions (layers) merge into
one layer at all proportions
• CST is also known as upper consolute temperature
• CST of phenol water system is 66.80C
• At any temperature above CST phenol and water are miscible
in all proportions
• Outside the curves, phenol and water are miscible
• The Tie line is represented by the line drawn parallel to
the base line from two points on the curve at any temperature in the phase
diagram of partially miscible liquids
Phenol-
Water System-Applications
• The phenol-water miscibility curve suggests that 76% w/w phenol
corresponds to 80 % w/v solution, which should be used in dispensing
• CST is a characteristic of a system and used for testing
the purity of a substance
• The method can be used to determine the percentage composition
of added component in the conjugate solution
Triethylamine-Water
System
• The temperature composition curve of trimethylamine and water
is shown below:
• The left hand side of the curve indicates the miscibility
of triethylamine in water
• The right hand side of the curve indicates the solubility
of water in triethylamine
• Lower consolute temperature is defined as the minimum
temperature at which the two conjugate solutions are miscible in all
proportions
• The lower consolute temperature for triethylamine-water
system is 18.50C
Nicotine-
Water System
• The temperature composition curve of nicotine –water
system is shown below:
• At room temperature, nicotine and water are miscible in
all proportions
• At higher temperature, the mutual solubility decreases
• This system exhibit both lower (60.80C) and upper (2080C) critical
solution temperature
Summary
• Solution-
Defined as a homogenous mixture in which one substance is said to dissolve in
the other
• Saturated
solutions- The solution in which the dissolved solute is in equilibrium
with the solvent phase, at a definite temperature
• Supersaturated
solution- Solution that contains more of the dissolved solute than that it
would normally contain at a definite temperature
• Whether or not a solute will dissolve in a solvent and the
extent in which it will dissolve
• The amount of a solute that will dissolve in a specific
solvent given condition
• When the temperature drops while you mix the solute and
solvent, raising the temperature will increase solubility
• The greater the surface area per unit mass, the quicker it
will dissolve
• The liquid-liquid intermolecular forces are not as strong
as the intermolecular forces between solid solute particles with the solvent.
• Miscible liquids-
Liquids that are miscible in all proportions are called as miscible liquids
• Raoult’s law –
It states that the partial vapour
pressure of each volatile constituents is equal to the vapour pressure of the
pure constituents multiplied by its mole fraction in the solution at a given
temperature
• Mathematical expression of Raoult’s law can be given by
PA= PA0 XA
PB= PB XB
• Ideal solution-
It is defined as the one in which there is no change in the properties of the
components other than dilution, when they are mixed to form a solution
• Non ideal or real
solution- Liquid mixtures that show varying degree of deviation from
Raoult’s law, are real or non-ideal solutions
• Positive deviations
from Raoult’s law- The systems in which the vapour pressure is greater than
the sum of the partial pressures of the individual components
• Phase – It is
defined as a homogenous physically distinct portion of a system that is
separated by bounding surfaces from each other
• Phase rule- can
be represented by:
F = C – P + 2
• Partially miscible
liquids – Partially miscible liquids or conjugate liquids are defined as a
two phase liquid system in which their mutual solubility in one another is limited
• Critical solution
temperature – The critical solution temperature (CST) is defined as maximum
temperature at which the two conjugate solutions (layers) merge into one layer
at all proportions
• Lower consolute
temperature – it is defined as the minimum temperature at
which the two
conjugate solutions are miscible in all proportions
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