Solution

.
Mixture & Solution??
● In a mixture, substances are generally just mixed, not completely dissolved & can be separated.

● In a solution, substances are dissolved completely and they cannot be separated.

 Solute + Solvent = Solution
A homogeneous mixture of two or more substances joined together physically is called
a solution. E.g., some salt into the water, it completely dissolve in the water to form a
homogeneous mixture or uniform composition. This homogeneous mixture of salt and
water is known as solution.

The components of solution The components of solution

which is present in Smaller which is present in Larger
amount. amount.
 Types of Solutions
Solutions can be any combination of solids, liquids, and gases. All solutions are described or
characterized by the state of matter of their solvent, not their solutes.
We can have six combinations:

Solid/Solid
Solid/Liquid
Solid/Gas
Liquid/Liquid
Liquid/Gas
Gas/Gas
 Properties of solutions
All solutions have these properties:

● A solution is a homogeneous mixture.

● Solutions are mixtures of a solvent and various solutes.
● Solute particles cannot be separated by filtration.
● Solutions are stable at given temperature.
● Solutions can be saturated, unsaturated, or supersaturated.
Solubility
Solubility is defined as ‘the maximum amount of a given solute that can dissolve
in a certain amount of a solvent at a specified temperature & pressure’ or a
measure of how much solute will dissolve in a solvent.
 Types of Solution (Based on Solubility)

■ Saturated Solution: A solution that contains the maximum amount of dissolved solute.
■ Unsaturated Solution: A solution that contains less amount of solute than the saturation
amount.
■ Supersaturated Solution: A solution that contains more solute than the saturation amount.
Factors Affecting Solubility of a Solute
Molecule
- Temperature
- Pressure
- Chemical natures of the solute and solvent.

Temperature:
- When a solid dissolves in a liquid, a change in the physical state of the
solid analogous to melting takes place. Heat is required to break the bonds
holding the molecules in the solid together.

- At the same time, heat is given off during the formation of new
solute -- solvent bonds. (hydration)

- If the heat given off in the hydration process is less than the heat required
to break apart the solid, the net dissolving reaction is endothermic (energy
required). The addition of more heat facilitates the dissolving reaction by
providing energy to break bonds in the solid. This is the most common
situation where an increase in temperature produces an increase in
solubility for solids.
■ Chemical natures of the solute and solvent
■ A polar solute will dissolve in a polar solvent but not in a nonpolar solvent. The adage
"like dissolves like" is very useful.
■ Example
■ Alcohol (polar substance) dissolves in water (polar substance)
■ Water (polar substance) does not dissolve in oil (nonpolar substance)

Pressure: Solution of Gas in Liquid

The solubility of a gas in a solvent depends on

the pressure and temperature
pH of the Solution
The solubility of a drug can be strongly influenced by the pH of the surrounding
environment, especially for ionizable compounds like weak acids and bases. The extent to
which a compound ionizes depends on the pH of the solution relative to its pKa value.
When the environment favors ionization, solubility typically increases because ionized
species are more hydrophilic and thus more readily dissolve in aqueous media.
For instance, a weak base such as domperidone maleate becomes more ionized in an
acidic medium (e.g., 0.1N HCl), leading to higher solubility. In contrast, in a neutral or
basic pH, ionization decreases and the compound may precipitate or exhibit reduced
solubility. This principle is commonly analyzed using the Henderson-Hasselbalch
equation, which links pH, pKa, and the ratio of ionized to unionized forms.
Particle Size
Particle size significantly impacts solubility through its influence on the surface area
available for dissolution. Smaller particles expose a larger surface area to the solvent,
thereby increasing the dissolution rate.
According to the Noyes–Whitney equation, the rate at which a substance dissolves is
directly proportional to the surface area. The equation is given below-

Therefore, reducing the particle size—through techniques like micronization or nanosizing

—not only accelerates the rate of dissolution but can also enhance the apparent solubility
of poorly soluble drugs. This is especially useful in pharmaceutical formulations where
bioavailability is linked to how quickly and completely the drug dissolves.
Polymorphism
■ Polymorphism refers to the ability of a compound to exist in multiple crystalline forms,
each with its own unique molecular packing, melting point, and solubility profile.
Different polymorphs of the same substance can show widely varying solubility
behaviors. Generally, amorphous forms (non-crystalline) have higher free energy and
dissolve more readily than their crystalline counterparts. Selecting the appropriate
polymorph is therefore critical in formulation development. For a drug like
domperidone maleate, choosing a more soluble but stable polymorph can significantly
improve its dissolution rate and overall performance in dosage forms.
●Units of Concentration
The concentration of a solution is defined as the amount of solute present in a given amount
of solution.
Problems for using Molarity and Normality

1. Volume of solution changes with temperature. So, it should

not be used when one wishes to study the properties of
solutions at various temperature.

2. Difficult to study the properties of solutions such as vapor

pressure and osmotic pressure which are related to the
concentration of the solvent.

3. Volume of the solvent in a molar or normal solution is not

always known.
 Vapor Pressure
■ When the liquid is heated, the energy of the molecules rises; it becomes lighter and
occupies the surface of the liquid. This process is known as ‘evaporation’. The
molecules which can be seen on the liquid surface are called ‘vapor’.
■ The evaporation continues at a constant rate the temperature of the liquid is kept
constant. When some molecules of the liquid in the vapor phase, strikes the walls of the
containers or the surface of the liquid, it may get converted back to the liquid phase.
This process is called condensation.
■ Vapor pressure, also known as vapor equilibrium pressure, can be defined as the
pressure exerted by a vapor with its condensed phases (solid or liquid) in a closed
system at a given temperature.

Initial Intermediate Equilibrium

Rate of Evaporation

Rate of Condensation
Raoult’s Law
In the 1880s, French chemist François-Marie Raoult discovered that,
When a substance is dissolved in a solution, the vapor pressure of the solution will
generally decrease. This observation depends on two variables:
■ The mole fraction of the amount of dissolved solute present, and
■ The original vapor pressure (pure solvent)

Adding a solute lowers vapor pressure because the additional solute particles
will fill the gaps between the solvent particles. This means less of the solvent
will be on the surface and less will be able to break free to enter the gas phase,
resulting in a lower vapor pressure.
Raoult’s Law (Non-volatile solute)
■ Raoult’s law is a chemical law that relates the solution’s vapour pressure to the mole fraction
of a solution added.
■ In case of a single volatile liquid (the solvent) and a non-volatile solute (e.g. salt in water) the
law will be-
“The vapor pressure of a solution of a non-volatile solute is equal to the vapor pressure of the
pure solvent at that temperature multiplied by its mole fraction.”

In equation form we can read it as:

0
P= P solv . Xsolv
Here,
P = Vapor pressure of the solution
0
P solv = Vapor pressure of the pure solvent at a particular temperature
Xsolv = Mole fraction of the solvent
Raoult’s Law (Volatile solute)
■ Even when a solute is volatile, meaning that it has a measurable vapor pressure, we can still use Raoult’s
law. In this case, we calculate the vapor pressure of each component separately.
■ In this case the law will be-
‘‘ The total vapor pressure of the solution (PT) is the sum of the vapor pressures of the components’’
Or,
“The vapor pressure of an ideal solution directly depends on the vapor pressure of each chemical
component and the mole fraction of the components present in the solution.”
Thus for two constituents A and B,
0
PA= PA . XA
0
PB= PB . XB

Here, PA and PB = the partial vapor pressures of the constituents in the solution
XA and XB = mole fractions of the constituents
0 0
PA and PB = vapor pressures of the pure components
So, the total vapor pressure P of the ideal solution containing components A and B is equal to :
P = PA + PB (XA+XB=1), two cons. in a sol.
0 0
= PA . XA +PB . XB
0 0
Graphical Representation
● Ideal Solution
■ The solutions which obey Raoult’s Law at
every range of concentration and at all
temperatures are called Ideal Solutions. We
can obtain ideal solutions by mixing two ideal
components having similar molecular size and
structure. For Example, consider two liquids A
and B, and mix them. The formed solution will
experience several intermolecular forces of
attractions inside it, which will be:
■ A – A intermolecular forces of attraction
■ B – B intermolecular forces of attraction
■ A – B intermolecular forces of attraction
■ The solution is said to be an ideal solution,
only when the intermolecular forces between A
– A, B – B and A – B are nearly equal.
● Non-Ideal/Real Solution
■ The solutions which don’t obey Raoult’s law at every range of concentration and at all
temperatures are called Non-Ideal Solutions.
■ Non-ideal solutions deviate from ideal solutions and are also known as Non-Ideal Solutions. Non-
ideal solutions are of two types:
1. Non-ideal solutions showing positive deviation from Raoult’s Law (Acetone and Benzene, Ethanol
and Water)
2. Non-ideal solutions showing negative deviation from Raoult’s Law (Chloroform and Benzene,
Chloroform and Diether, Acetone and Aniline)
● Positive Deviation from Raoult’s Law
■ Positive Deviation from Raoult’s Law occurs when the vapor
pressure of the component is greater than what is expected in
Raoult’s Law.
■ For Example, consider two components A and B to form non-ideal
solutions. Let the vapor pressure, pure vapor pressure and mole
0
fraction of component A be PA , PA and xA respectively and that of
0
component B be PB , PB and xB respectively.
0 0 0 0
■ PA > PA xA and PB > P B xB, as the total vapor pressure (PA xA + P B
xB) is greater than what it should be according to Raoult’s Law.
● The solute-solvent forces of attraction is weaker than solute-
solute and solvent-solvent interaction that is, A – B < A – A or B –
B
● The enthalpy of mixing is positive that is, ∆mix H > 0 because the
heat absorbed to form new molecular interaction is less than the
heat released on breaking of original molecular interaction
● The volume of mixing is positive that is, ∆mix V > 0 as the volume
expands on the dissolution of components A and B
● Negative Deviation from Raoult’s Law

■ Negative Deviation occurs when the total vapour pressure is less

than what it should be according to Raoult’s Law. Considering the
same A and B components to form a non-ideal solution, it will
show negative deviation from Raoult’s Law only when:
0 0 0 0
● PA < PA xA and PB < P B xB as the total vapor pressure (PA xA + P B xB)
is less than what it should be with respect to Raoult’s Law

● The solute-solvent interaction is stronger than solute-solute and

solvent-solvent interaction that is, A – B > A – A or B – B

● The enthalpy of mixing is negative that is, ∆mix H < 0 because more
heat is released when new molecular interactions are formed

● The volume of mixing is negative that is, ∆mix V < 0 as the volume
decreases on the dissolution of components A and B
Henry’s Law (Solution of Gas)
■
Limitation of Henry’s law:
It applies closely to gases with nearly ideal behavior
At moderate temperature and pressure
If the solubility of the gas in the solvent is low
The gas does not react with the solvent to form new species. So ammonia gas in water
does not follow Henry’s law
The gas does not associate or dissociate in the solvent
 Distribution of solids between two immiscible liquids

If we take two immiscible solvents A and B in a beaker, they form separate layers. When a
solute X which is soluble in both solvents is added, it gets distributed or partitioned between
them. Molecules of X pass from solvent A to B and from solvent B to A. Finally a dynamic
equilibrium is set up. At equilibrium, the rate, at which molecules of X pass from one solvent to
the other is balanced.
■ Nernst Distribution Law (Distribution/Partition law)
“When a solute is shaken up with two liquids which are immiscible with each other, but in both of which
the solute is soluble, then the solute distributes itself between the liquids in such a way that the ratio of
the concentrations of the solute in the two liquids is a constant at a constant temperature, provided
the solute is in the same molecular condition in two liquids.”
If C1 and C2 are the concentrations of the solute in solvent 1 and solvent 2 respectively, then according
to this law:
C1/ C2 = KD = Distribution co-efficient or partition co-efficient
When a solute is shaken with two non-miscible solvents, at equilibrium both the solvents are
saturated with the solute. Since the solubility also represents concentration, we can write the
distribution law as:

C1/C2 = S1/S2 = KD

So basically solutes partition or distributes themselves into the two immiscible liquids according to their
differences in solubility in those liquids.
Limitation of Distribution law
● Constant temperature: Temperature is kept constant throughout the experiment

● Same molecular state: No association or dissociation

● Equilibrium concentration: Concentration of solute are noted after the equilibrium has
been established

● Dilute solution: Suitable if solute concentration is low

● Non-miscibility of solvent: Immiscible or only slightly soluble. The extent of mutual

solubility of solvent remain unaltered by the addition of solute to them
Solvent Extraction

Solvent extraction is the process in which a

compound transfers from one solvent to another
owing to the difference in solubility or
distribution coefficient between these two
immiscible (or slightly soluble) solvents.

● Liquid/liquid,

● Liquid/solid and

● Acid/base
Application of Distribution Co-
efficient: solvent extraction
Suppose we have 100 ml of aqueous solution containing A grams of an organic compound. We can extract the
substance with 100 ml of ether at a time or in two portion of 50 ml each.

Let the distribution co-efficient is 2 in favor of ether.

Using single extraction:

Amount of substance extracted in ether is x gram
Amount of substance left in aqueous solution is (A-x) gram

Concentration of substance in ether = x/100

Concentration of substance in water = (A-x)/100

So, Cether/Cwater = 2

(x/100) / (A-x)/100 = 2

X = 2/3A i.e 66% substance is extracted

●Problems