Lecture 1 Introduction to Solubility

What is Solution? 

It is defined as a type of homogenous mixture which is formed by minimum two or more than two
chemical substances. Homogenous means a sample which is in one type of state or phase and said to have
uniform composition throughout. In a lay man term, It tells that the substances which is mixed to give a
solution cannot be differentiated due to uniformity.

E.g.: Salt- water, Rubbing- alcohol (Sanitizer), Sugar- water, Oxygen- CO2 solutions etc. When we look
closely, on mixing salt in water with stirring, the final solution do not show any salt particle in water this
makes it homogenous salt solution mixture (It means combination of two or more substances in some
specific ratio).

All the three states of matter (gas, liquid or solid) may behave either as solvent or solute. Depending on the
state of solute or solvent, mainly there may be the following seven types of binary solutions.

Solution Characteristics

A solution exhibits various important properties like:

 A solution is generally a homogenous mixture.

 A homogenous solution is present in one phase / state (e.g. Solid / liquid / gas).
 The particles of solution are extremely small so they are not visible to the naked eye.
 Since particles of solution is present in one phase they do not scatter a beam of light passing
through it or do not show tyndall effect.
 Since the particles of solution is mixed uniformly it is stable and does not settle down with time.
 The solute particle added are so minute that they cannot be separated by filtering.

Solution components are:

Solute: is the substance being dissolved; present in less quantity.

Solvent: is the substance doing the dissolving; present in large quantity.

Types of Solutions:
1. Aqueous solution: Solutions that contain water as the solvent. Ex. sugar in water, carbon dioxide
in water, etc.
2. Non-Aqueous Solution:  Solutions that contain a solvent other than water like Ether, benzene,
petrol, carbon tetrachloride etc Ex. sulfur in carbon disulphide, naphthalene in benzene, etc.
3. Unsaturated Solution: A solution is said to be unsaturated when the solvent (e.g. water)
is capable of dissolving more solute (e.g. Sugar) at a (definite/fixed) temperature. Ex: 1% NaCl solution.(1
g of NaCl in 99 ml pure water)
4. Saturated Solution: A solution is said to be saturated when the solvent is not capable of dissolving
any more solute at a (definite/fixed) temperature. Ex: 40% NaCl solution
5. Supersaturated Solution: A solution is said to be super saturated when the solute is present in
excess amount and dissolved forcefully by increasing temperature or pressure. They generally crystal out
in bottom by the method called crystallization. Ex: 70% NaCl solution
 On the basis of Concentration of Solute in two Solutions,

(Let’s consider a system containing a solution in beaker and inside that solution a Biological
cell is kept, this cell contain a liquid in it, all together we have two liquids in this system)

 Isotonic Solution: The two solutions that have the same concentration of a solute in it so
water moves across the cell membrane in both directions maintaining cell size. Ex: A solution of 0.9%
NaCl.
 Hypertonic Solution: The solution kept in beaker has higher concentration of solute in it so
water comes out of the cell and into the solution in beaker causing the cell to plasmolyze/shrink
Ex: 1.5% NaCl solution
 Hypotonic Solution: The solution kept in beaker has lower concentration of solute in it so
water moves into the cell causing cells to swell up and finally burst. Ex: Water, 0.5% NaCl solution

Lecture 2 Methods to Expressing

Concentration
Lecture 2 Methods to Expressing
Concentration
Concentration of Solution:

The Concentration of a Solution is defined as the relative amount of solute present in a solution.

It basically talks about how to find the amount of solute present in solvent which together forms
solution.There are various methods used to find this,

Methods of Expressing Concentration of Solutions

 Percentage by weight (w / w %)
 Percentage by volume (V / V%)
 Weight by volume (w / v%)
 Mole fraction (x)
 Parts per million (ppm)
 Molarity (M)
 Molality (m)
 Normality (N)

 1) Percentage by Weight

Symbol: (w / w %)

Definition: It is defined as the amount of solute present in 100 g of solution.

Unit: No unit
2) Percentage by Volume

Symbol: (V / V %)

Definition: It is defined as the volume of solute present in 100 mL of solution.

Unit: No unit

3) Weight by Volume

Symbol: (W / V %)

Definition: It is defined as the amount of solute present in 100 mL of solution.

Unit: mg/L

Formula:

Percent Concentration

Example:

As an example consider 5 g sugar dissolved in 20 g of water. What is the w/w% concentration of

sugar in this solution?

4) Mole Fraction

Symbol : X ( lower-case Greek letter chi, χ)

 It is the ratio of the number of moles of solute and the total number of moles of solute and solvent.

Unit: No unit

Formula:
Mole Fraction (X): This is the number of moles of a compound divided by the total number of moles of all
chemical species in the solution.

Example:

What are the mole fraction of the components of the solution formed when 92 g glycerol is mixed
with 90 g water? (molecular of weight water = 18; molecular weight of glycerol = 92)

90 g water = 90 g x 1 mol / 18 g = 5 mol water

92 g glycerol = 92 g x 1 mol / 92 g = 1 mol glycerol

Total mol = 5 + 1 = 6 mol

X water = 5 mol / 6 mol = 0.833

X glycerol = 1 mol / 6 mol = 0.167

It’s a good idea to check your math by making sure the mole fractions add up to 1:

xwater + xglycerol = .833 + 0.167 = 1.000

5) Parts Per Million

Symbol: ppm

Definition: It is defined as the parts of a component per million parts (10 6) of the solution. It is widely used
when a solute is present in trace quantities.

Unit: ppm

Formula:

Example:
Calculate the molar concentration of 2000 ppm of Pb2 + (A. M. = 207 g/mol)?

Solution:

PPM = M x M. M.x1000

6) Molarity:

Symbol : M

Definition: Molarity of any solution is number of moles of solute per liter of solution

Unit: mol/litre

Formula:

Molarity = Number of moles of solute / Volume of solution in liter.

Example:

What is the molarity of a solution containing 0.32 moles of NaCl in 3.4 liters?

Solution:

      = 0.94 M NaCl

7) Molality

Symbol: m

Definition: Molality of any solution is represented as the number of moles of solute present per kg
of solvent

Unit: mol/kg

Formula:
 Molality(m) = Number of moles of solute / Mass of solvent in Kg

Note: Why m is not affected by change in temperature?

Since it is dependent on mass of solute and mass do not change to small shift in temperature due to close
packing of solid atoms therefore it is independent of temperature change.

Lecture 3 Factors Affecting Solubility

Solubility of solids in liquid

Factors affecting solubility of solid solute in liquid solvent:

 Nature of the solute and solvent.

 Effect of Temperature.
Nature of the Solute and Solvent

There is a scientific proverb that “LIKE DISSOLVE LIKE*” Keeping this as bench mark, we
can tell that ionic/polar compounds like NaCl, KCl gets dissolved in polar solvent like water
and the non-polar/covalent or organic molecules can dissolve in non-polar compounds like
benzene can be dissolved in acetone.

LIKE DISSOLVE LIKE Principle-IT DEPENDS ON TYPES OF BOND / polarity of

molecules / IMF BETWEEN SOLUTES AND SOLVENT.

1) Nature of solute 

 The solutes (solids) can be classified as ionic and non-ionic solids.

 The ionic solids consist of positively and negatively charged ions.
 It is the force of attraction between the ions, i.e., lattice energy which opposes the tendency of
a solute to dissolve. This force of attraction is different in different ionic solids depending on the
charges present on the ions and distance between ions (ionic radii).
 The ionic solutes having high less lattice energy have more solubility. The ions are solvated
by the solvent molecules and in this process energy (known as hydration energy) is released. When
the hydration energy is high, the ionic solid is more soluble.
  Many non-ionic substances dissolve in polar solvents due to hydrogen bonding. Generally, if
the solute and solvent have similar characteristics, i.e. both polar or both non-polar, the solubility is
high and if both are dissimilar, the solubility is found low.  

2) Nature of solvent
 Ionic solids dissolve to a larger extent in a solvent having a high dielectric constant as
compared to solvents of low dielectric constants. 
 Dielectric constant of water is 80 while that of methyl alcohol is 33.5 an ionic solid, therefore,
dissolves more readily in water than in methyl alcohol.
 Benzene has a very low dielectric constant of 2.3 and, hence, ionic solids do not dissolve in
benzene.
 For non-ionic solids, the guiding principle is ‘like dissolves like, i.e., if the solvent is polar, it
will dissolve the polar solutes and if it is non-molar, it will dissolve the non-polar solutes in it. 

3) Effect of temperature: It has 3 cases.

i) The solubility of solid is directly proportional to temperature when the process of

dissolution is endothermic (When heat is absorbed).

(Solute + Solvent + Heat → Solution)

For Example: NaCl, KCl etc.

ii) The solubility of solid decreases with increase of temperature when the process of
dissolution is exothermic (When heat comes out). 

(Solute + Solvent → Heat + Solution)

For Example:  Na CO , H O etc

2 3 2

iii) Solids whose solubility does not increase or decrease with temperature fluctuation.

For Example: CaCl , 6H O 2 2

Solubility of solid in liquid is also dependent on:

 Size of solute
 Nature of Solute-Amorphous or crystalline
 Surface area of solute
 Amount of solvent used
 Container size

2. Solubility of Gas in Liquid

Factors affecting solubility of gaseous solute in liquid solvent:                

 Temperature
 Pressure
 i) Temperature

Cold Liquid can dissolve more amount of gas but as temperature rises, the solubility of gas
decreases. Rise in temperature causes an elevation in kinetic energy of gas molecules due to
fast motion of gas molecules. Increased kinetic energy causes fast motion and the molecules
collide with each other and even with wall of container this break intermolecular bonds and
the gases escapes out easily from solution.

Examples we see around:

 Recall the cold drink can scenario when you open and keep it at room temperature the
dissolved CO2 escapes and the drink gives a very flat taste and non-fizzy.
 Thermal power plants that discharges the hot water into water bodies like ponds / rivers /
lakes may kill the fish by decreasing the dissolved oxygen concentration in it.
 Imagine how the fishes and other aquatic life survive inside the water bodies in polar areas
where water if freezed on top.
ii) Pressure

Gases like hydrogen, oxygen, nitrogen etc. get mixed/dissolved in water to a small extent but
gases like NH , CO , HCl are highly soluble in water.
3 2

The higher solubility of these gases CO , NH , HCl  are because they react with solvent. This
2 3

greater solubility of the gas in a solvent is due to their chemical similarity.

It has been found that the gas solubility in liquid increases with increase in pressure

The effects of pressure on the solubility of gases in liquid can be best described through a
combination of Henry's law and Le Châtelier principle.

Henrys law:

It was given by William Henry in 1803 and it states that:

“The amount of gas that dissolves in a given liquid is directly proportional to the partial
pressure of that gas.”

                              OR

“The mass of a gas dissolved by a given volume of a liquid, at constant temperature, is

proportional to the pressure of the gas”.

It is used to do solubility based calculations

Mathematical form of Henry's law / Henrys Solubility Formula:

P=KC H

P = Partial pressure of the solute.

C = Is the concentration of the solute.

 K  = Henrys law constant which is different for each solute-solvent pair.                               
H

There are some things to remember when working with this law:

 Henry’s law only works if the molecules are at equilibrium and if the same molecules are
present throughout the solution.
 Henry’s law does not apply to gases at extremely high pressures.
 Henry’s law does not apply if there is a chemical reaction between the solute and the solvent.
For example, HCl (g) reacts with water in the dissociation reaction and affects solubility, so Henry’s
law cannot be used in this instance.
 If Henry’s law is used to denote how the concentration will change with pressure, the
following equation is used: P1/C1=P2/C2

Applications of Henry's Law

Production of Carbonated Beverages: To increase the solubility of CO  in soft drinks and
2

soda water, the bottle is sealed under high pressure.When the bottle is opened under normal
atmospheric conditions, the pressure inside the bottle falls to atmospheric pressure and the
excess CO2, bubbles out of the solution causing the effervescence.

cument
Lecture 3 Factors Affecting Solubility
Lecture 3 Factors Affecting Solubility
 Solubility of solids in liquid

Factors affecting solubility of solid solute in liquid solvent:

o Nature of the solute and solvent.

o Effect of Temperature.

Nature of the Solute and Solvent

 source: https://www.askiitians.com/iit-jee-solutions-colligative-properties/solubility/

There is a scientific proverb that “LIKE DISSOLVE LIKE*” Keeping this as bench mark, we
can tell that ionic/polar compounds like NaCl, KCl gets dissolved in polar solvent like water
and the non-polar/covalent or organic molecules can dissolve in non-polar compounds like
benzene can be dissolved in acetone.

LIKE DISSOLVE LIKE Principle-IT DEPENDS ON TYPES OF BOND / polarity of

molecules / IMF BETWEEN SOLUTES AND SOLVENT.

1) Nature of solute 

o The solutes (solids) can be classified as ionic and non-ionic solids.

o The ionic solids consist of positively and negatively charged ions.
o It is the force of attraction between the ions, i.e., lattice energy which opposes the
tendency of a solute to dissolve. This force of attraction is different in different ionic solids depending
on the charges present on the ions and distance between ions (ionic radii).
o The ionic solutes having high less lattice energy have more solubility. The ions are
solvated by the solvent molecules and in this process energy (known as hydration energy) is released.
When the hydration energy is high, the ionic solid is more soluble.
o  Many non-ionic substances dissolve in polar solvents due to hydrogen bonding.
Generally, if the solute and solvent have similar characteristics, i.e. both polar or both non-polar, the
solubility is high and if both are dissimilar, the solubility is found low.  

2) Nature of solvent

o Ionic solids dissolve to a larger extent in a solvent having a high dielectric constant as
compared to solvents of low dielectric constants. 
o Dielectric constant of water is 80 while that of methyl alcohol is 33.5 an ionic solid,
therefore, dissolves more readily in water than in methyl alcohol.
o Benzene has a very low dielectric constant of 2.3 and, hence, ionic solids do not
dissolve in benzene.
o For non-ionic solids, the guiding principle is ‘like dissolves like, i.e., if the solvent is
polar, it will dissolve the polar solutes and if it is non-molar, it will dissolve the non-polar solutes in
it. 

3) Effect of temperature: It has 3 cases.

i) The solubility of solid is directly proportional to temperature when the process of

dissolution is endothermic (When heat is absorbed).

(Solute + Solvent + Heat → Solution)

For Example: NaCl, KCl etc.

 ii) The solubility of solid decreases with increase of temperature when the process of
dissolution is exothermic (When heat comes out). 

(Solute + Solvent → Heat + Solution)

For Example:  Na CO , H O etc

2 3 2

iii) Solids whose solubility does not increase or decrease with temperature fluctuation.

For Example: CaCl , 6H O

2 2

Solubility of solid in liquid is also dependent on:

o Size of solute
o Nature of Solute-Amorphous or crystalline
o Surface area of solute
o Amount of solvent used
o Container size

2. Solubility of Gas in Liquid

Factors affecting solubility of gaseous solute in liquid solvent:                

o Temperature
o Pressure

i) Temperature

Cold Liquid can dissolve more amount of gas but as temperature rises, the solubility of gas
decreases. Rise in temperature causes an elevation in kinetic energy of gas molecules due to
fast motion of gas molecules. Increased kinetic energy causes fast motion and the molecules
collide with each other and even with wall of container this break intermolecular bonds and
the gases escapes out easily from solution.

Examples we see around:

o Recall the cold drink can scenario when you open and keep it at room temperature the
dissolved CO2 escapes and the drink gives a very flat taste and non-fizzy.
o Thermal power plants that discharges the hot water into water bodies like ponds /
rivers / lakes may kill the fish by decreasing the dissolved oxygen concentration in it.
o Imagine how the fishes and other aquatic life survive inside the water bodies in polar
areas where water if freezed on top.
ii) Pressure

Gases like hydrogen, oxygen, nitrogen etc. get mixed/dissolved in water to a small extent but
gases like NH , CO , HCl are highly soluble in water.
3 2

The higher solubility of these gases CO , NH , HCl  are because they react with solvent. This
2 3

greater solubility of the gas in a solvent is due to their chemical similarity.

It has been found that the gas solubility in liquid increases with increase in pressure

Figure: A Model Depicting Why the Solubility of a Gas Increases as the Partial Pressure Increases
at Constant Temperature

Source: https://2012books.lardbucket.org/books/principles-of-general-chemistry-v1.0/s17-04-
effects-of-temperature-and-pre.html

The effects of pressure on the solubility of gases in liquid can be best described through a
combination of Henry's law and Le Châtelier principle.

Henrys law:

It was given by William Henry in 1803 and it states that:

“The amount of gas that dissolves in a given liquid is directly proportional to the partial
pressure of that gas.”

                              OR

“The mass of a gas dissolved by a given volume of a liquid, at constant temperature, is

proportional to the pressure of the gas”.

It is used to do solubility based calculations

Mathematical form of Henry's law / Henrys Solubility Formula:

P = KHC

P = Partial pressure of the solute.

C = Is the concentration of the solute.

K  = Henrys law constant which is different for each solute-solvent pair.                               

H
 There are some things to remember when working with this law:

o Henry’s law only works if the molecules are at equilibrium and if the same molecules
are present throughout the solution.
o Henry’s law does not apply to gases at extremely high pressures.
o Henry’s law does not apply if there is a chemical reaction between the solute and the
solvent. For example, HCl (g) reacts with water in the dissociation reaction and affects solubility, so
Henry’s law cannot be used in this instance.
o If Henry’s law is used to denote how the concentration will change with pressure, the
following equation is used: P1/C1=P2/C2

Applications of Henry's Law

Production of Carbonated Beverages: To increase the solubility of CO  in soft drinks and
2

soda water, the bottle is sealed under high pressure.When the bottle is opened under normal
atmospheric conditions, the pressure inside the bottle falls to atmospheric pressure and the
excess CO2, bubbles out of the solution causing the effervescence.

At high altitudes

The partial pressure of oxygen is less than that at the ground level. This leads to low
concentrations of oxygen in the blood and tissues of people living at high altitudes or
climbers. Low blood oxygen causes climbers to become weak and unable to think clearly,
symptoms of a condition known as anoxia.

Decompression Sickness or “The Bends”

o In order for deep-sea divers to breathe underwater, they must inhale highly
compressed air in deep water, resulting in more nitrogen dissolving in their blood, tissues, and joints.
If a diver returns to the surface too rapidly, the nitrogen gas diffuses out of the blood too quickly,
causing pain and possibly death. This condition is known as “the bends.”To prevent the bends, a diver
must return to the surface slowly, so that the gases will adjust to the partial decrease in pressure and
diffuse more slowly. A diver can also breathe a mixture of compressed helium and oxygen gas, since
helium is only one-fifth as soluble in blood as nitrogen. Underwater, our bodies are similar to a soda
bottle under pressure. Imagine dropping the bottle and trying to open it. In order to prevent the soda
from fizzing out, you open the cap slowly to let the pressure decrease. On land, we breathe about 78
percent nitrogen and 21 percent oxygen, but our bodies use mostly the oxygen. When we’re
underwater, however, the high pressure of water surrounding our bodies causes nitrogen to build up in
our blood and tissues. Like in the case of the bottle of soda, if we move around or come up from the
water too quickly, the nitrogen will be released from our bodies too quickly, creating bubbles in our
blood and causing “the bends.

Lecture 4 Raoult's Law

 Introduction

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:

1. the mole fraction of the amount of dissolved solute present and

2. the original vapor pressure (pure solvent).

At any given temperature for a particular solid or liquid, there is a pressure at which the vapor formed
above the substance is in dynamic equilibrium with its liquid or solid form. This is the vapor pressure of
the substance at that temperature. At equilibrium, the rate at which the solid or liquid evaporates is equal to
the rate that the gas is condensing back to its original form. All solids and liquids have a vapor pressure,
and this pressure is constant regardless of how much of the substance is present.

Vapour Pressure

Consider a pure liquid in a beaker is covered with a jar. Some molecules on the liquid surface evaporate
and fill the vacant space available to them. The molecules in the vapor phase move randomly in the vacant
space, during this motion, they strike the surface of the liquid and condensed. This process of evaporation
and condensation go on and an equilibrium is established between evaporation and condensation. The
pressure exerted by vapors over the liquid surface at equilibrium is called vapour pressure of the liquid.

The partial vapour pressure of any component in the solution is directly proportional to its mole
fraction”. PA = KXA 

Where, PA = Partial vapour pressure of A

XA  =  Mole fraction of A in solution

For pure liquids XA = 1

Then K = P0A Where P0A  is the vapour pressure of component A in pure state

Hence, PA = XAP0A 

Similarly for component B , PB = XBP0A

Roults law  is applied for a solution of liquid in liquids 

A simple explanation of Why Raoult's Law works?

There are two ways of explaining why Raoult's Law works - a simple visual way, and a more sophisticated
way based on entropy. Because of the level I am aiming at, I'm just going to look at the simple way.

Remember that saturated vapour pressure is what you get when a liquid is in a sealed container. An
equilibrium is set up where the number of particles breaking away from the surface is exactly the same as
the number sticking on to the surface again
 Now suppose you added enough solute so that the solvent molecules only occupied 50% of the surface of
the solution.

A certain fraction of the solvent molecules will have enough energy to escape from the
surface (say, 1 in 1000 or 1 in a million, or whatever). If you reduce the number of solvent
molecules on the surface, you are going to reduce the number which can escape in any given
time.

But it won't make any difference to the ability of molecules in the vapour to stick to the
surface again. If a solvent molecule in the vapour hits a bit of surface occupied by the solute
particles, it may well stick. There are obviously attractions between solvent and solute
otherwise you wouldn't have a solution in the first place.

The net effect of this is that when equilibrium is established, there will be fewer solvent
molecules in the vapour phase - it is less likely that they are going to break away, but there
isn't any problem about them returning.

If there are fewer particles in the vapour at equilibrium, the saturated vapour pressure is
lower.

Ideal and Non – Ideal Solutions

The solutions which obey Raoult’s law at all compositions of solute in solvent at all
temperature are called ideal solutions.

Ideal solutions can be obtained by mixing two components with identical molecular size,
structure and they should have almost same inter molecular attraction e.g., two liquids A and
B form an ideal solution when A –A and B–B molecular attractions will be same and hence
A–B molecular attraction will be almost same as A–A and B–B molecular attraction.

An ideal solution should have following characteristics

 It should obey Raoult’s law i.e., PA = XA and PB = XB  

 Hmixing = 0, i.e. no heat should be absorbed or evolved during mixing
 Vmixing = 0, i.e. no expansion or contraction on mixing ?

Examples of Ideal solutions

 Ethyl chloride and ethyl bromide

 n–hexane and n–heptane
 CCl4 and SiCl4

The solution which deviate from ideal behaviour are called  non ideal solution  or real solutions and they
do not obey Raoult’s law over entire range of composition.

It has been found that on increasing dilution, a non ideal solution tend to be ideal.

For non ideal solutions,

 PA   XAP0A
 Hmixing   0,
  Vmixing = 0

Here we may have two cases 

Case 1:

Such a solution show positive deviation from Raoult’s Law and the observed boiling point of such
solutions is found to be less than the calculated value. e.g. cyclohexane and ethanol. In ethanol the
molecules are held together due to hydrogen bonding, when cyclohexane is added to ethanol the molecules
of cyclohexane tend to occupy the space between ethanol molecules due to which some hydrogen bonds
break due to which inter molecular attraction between cyclohexane and ethanol is reduced and hence show
higher vapour pressure.

Examples of solutions showing positive deviation:

 Acetone + Ethanol
 Acetone- Benzene
 Water + Methanol
 Water + Ethanol

Case 2:

Solutions of above type show negative deviation from Raoult’s law and their observed boiling point is
found to be higher than the calculated value eg. When acetone and chloroform are mixed together a
hydrogen bond is formed between them which increases inter molecular attraction between them and hence
decreases the vapour pressure
 Examples of solutions showing negative deviation:

 Acetone + Aniline
 Chloroform + Diethyl ether
 Chloroform + Benzene 
 Water + HCl
Condition for forming non-ideal solution showing positive deviation

Two liquids A & B on mixing form this type of solutions when

 A-B attractive force should be weaker than A-A and B-B attractive force.
 “A” and “B” have different shape, size and character.
 “A” and “B” escape easily showing higher vapour pressure than the expected value.

Figure: Positive Deviations to Raoult's Law

Source: https://www.sciencedirect.com/topics/chemistry/raoults-law

Condition for forming non-ideal solution showing negative deviation

Two liquids A & B on mixing form this type of solutions when

 A-B attractive force should be greater than A-A and B-B attractive force.
 “A” and “B” have different shape, size and character.
 Escaping tendency of both “A” and “B” is lower showing lower vapour pressure than expected
ideally. 

Figure: Negative Deviation to Raoult's Law

Lecture 5 Solubility Parameter

Solutions and Molecules

A solvent, usually thought of as a liquid, is a substance that is capable of dissolving other

substances and forming a uniform mixture called a solution. The substance dissolved is called
the solute and is usually considered to be the component present in the smallest amount.
According to this definition, an almost-dry or slightly swollen resin film comprises a solution
of a liquid (the solute) in a resin (the solvent), even though conventionally the liquid is
usually referred to as the solvent, and the resin as the solute.
Molecular Attractions

Liquids (and solids) differ from gases in that the molecules of the liquid (or solid) are held
together by a certain amount of intermolecular stickiness. For a solution to occur, the solvent
molecules must overcome this intermolecular stickiness in the solute and find their way
between and around the solute molecules. At the same time, the solvent molecules
themselves must be separated from each other by the molecules of the solute. This is
accomplished best when the attractions between the molecules of both components are
similar. If the attractions are sufficiently different, the strongly attracted molecules will cling
together, excluding the weakly attracted molecules, and immiscibility (not able to be mixed)
will result. Oil and water do not mix because the water molecules, strongly attracted to each
other, will not allow the weakly, attracted oil molecules between them.

Van der Waals Forces

These sticky forces between molecules are called van der Waals forces (after Johannes van
der Waals who first described them in 1873). Originally thought to be small gravitational
attractions, Van der Waals forces are actually due to electromagnetic interactions between
molecules.

The outer shell of a neutral atom or molecule is composed entirely of negatively charged
electrons, completely enclosing the positively charged nucleus within. Deviations in the
electron shell density, however, will result in a minute magnetic imbalance, so that the
molecule as a whole becomes a small magnet, or dipole. These electron density deviations
depend on the physical architecture of the molecule: certain molecular geometries will be
strongly polar, while other configurations will result in only a weak polarity. These
differences in polarity are directly responsible for the different degrees of intermolecular
stickiness from one substance to another. Substances that have similar polarities will be
soluble in each other but increasing deviations in polarity will make solubility increasingly
difficult.

Van der Weals forces, then, are the result of intermolecular polarities. As we shall see,
accurate predictions of solubility behavior will depend not only on determining the result of
intermolecular attractions between molecules, but in discriminating between
different types of polarities as well. A single molecule, because of its structure, may exhibit
van der Waals forces that are the additive result of two or three different kinds of polar
contributions. Substances will dissolve in each other not only if their intermolecular forces
are similar, but particularly if their composite forces are made up in the same way.

The Hildebrand Solubility Parameter

It is the total van der Waals force, however, which is reflected in the simplest solubility
value: the Hildebrand solubility parameter. The solubility parameter is a numerical value that
indicates the relative solvency behavior of a specific solvent. It is derived from the cohesive
energy density of the solvent, which in turn is derived from the heat of vaporization. What
this means will be clarified when we understand the relationship between vaporization, van
der Waals forces, and solubility.
Vaporization

When a liquid is heated to its boiling point, energy (in the form of heat) is added to the liquid,
resulting in an increase in the temperature of the liquid. Once the liquid reaches its boiling
point, however, the further addition of heat does not cause a further increase in temperature.
The energy that is added is entirely used to separate the molecules of the liquid and boil them
away into a gas. Only when the liquid has been completely vaporized will the temperature of
the system again begin to rise. If we measure the amount of energy (in calories) that was
added from the onset of boiling to the point when all the liquid has boiled away, we will have
a direct indication of the amount of energy required to separate the liquid into a gas, and thus
the amount of van der Waals forces that held the molecules of the liquid together.

It is important to note that we are not interested here with the temperature at which the liquid
begins to boil, but the amount of heat that has to be added to separate the molecules. A liquid
with a low boiling point may require considerable energy to vaporize, while a liquid with a
higher boiling point may vaporize quite readily, or vise versa. What is important is the energy
required to vaporize the liquid, called the heat of vaporization. (Regardless of the
temperature at which boiling begins, the liquid that vaporizes readily has less intermolecular
stickiness than the liquid that requires considerable addition of heat to vaporize.)

Cohesive Energy Density

From the heat of vaporization, in calories per cubic centimeter of liquid, we can derive
the cohesive energy density (c) by the following expression

where:

c=Cohesive energy density

Δh=Heat of vaporization

r=Gas constant

t=Temperature

V  = Molar volume
m

In other words, the cohesive energy density of a liquid is a numerical value that indicates the
energy of vaporization in calories per cubic centimeter, and is a direct reflection of the degree
of van der Waals forces holding the molecules of the liquid together.

Interestingly, this correlation between vaporization and van der Waals forces also translates
into a correlation between vaporization and solubility behavior. This is because the same
intermolecular attractive forces have to be overcome to vaporize a liquid as to dissolve it.
This can be understood by considering what happens when two liquids are mixed: the
molecules of each liquid are physically separated by the molecules of the other liquid, similar
to the separations that happen during vaporization. The same intermolecular van der Waals
forces must be overcome in both cases.

Since the solubility of two materials is only possible when their intermolecular attractive
forces are similar, one might also expect that materials with similar cohesive energy density
values would be miscible. This is in fact what happens.

Solubility Parameter

In 1936 Joel H. Hildebrand (who laid the foundation for solubility theory in his classic work
on the solubility of nonelectrolytes in 1916) proposed the square root of the cohesive energy
density as a numerical value indicating the solvency behavior of a specific solvent.

It was not until the third edition of his book in 1950 that the term "solubility
parameter" was proposed for this value and the quantity represented by the symbol ∂.
Subsequent authors have proposed that the term hildebrands be adopted for solubility
parameter units, in order to recognize the tremendous contribution that Dr. Hildebrand has
made to solubility theory.

Units of Measurement

The SI unit for expressing pressure is the pascal, and SI Hildebrand solubility parameters are
expressed in mega-pascals (1 mega-pascal or mpa=I million pascals). Conveniently, SI
parameters are about twice the value of standard parameters:

The importance of solubility parameter (3P) lies in predicting whether or not two substances
will mix. When two

substances are mixed to form a solution, the potential energy of each molecular species will
be changed by the change in the nature of new surrounding molecules. The greater the
difference between the potential energies of the two species, the greater will be the potential
energy change on mixing. The latter is compensated by the heat of mixing. In
thermodyanamic terms, two components will mix only if the free energy decreases.

Lecture 6 Partially Miscible Liquids

Partially Miscible Liquids

A pair of liquids 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 and is the general
case for a pair of liquids where one is polar and the other non-polar (such as water and
vegetable oil.) Another case that is commonly used in the organic chemistry laboratory is the
combination of diethyl ether and water. In this case, the differential solubility in the
immiscible solvents allows the two-phase liquid system to be used to separate solutes using
a separating funnel.

Conjugate solutions:  Many liquids are partially miscible and form two liquid layers at a
particular temperature. Such liquid solutions in which different compositions of components
coexist are called conjugate solutions, for example, phenol and water.

Critical temperature: The miscibility of liquids varies with temperature. At a certain

temperature the two layers become completely miscible. This temperature is called critical
temperature or consolute temperature

Degree of miscibility may be dependent on the temperature

1.Solubility increases with increase in temperature (water-phenol)

2.Solubility decreases with increase in temperature (water-triethylamine)

3.Solubility increases with increase & decrease in temperature (water-nicotine)

4.Solubility not affected by temperature In case of three component system the third liquid
may influence the degree of solubility of the 2 liquid systems. 

1) Phenol-Water System

•Point a, system containing 100% pure water.

•Addition of phenol to water will result in the formation of a single liquid phase until the
point b is reached.

•At point b, appears a second phase.

•Phase A: water rich phase containing 11% phenol

•Phase B: phenol rich phase containing 63% phenol

•increasing quantities of phenol, i.e., as we proceed across the diagram from point b to point
c, we form systems in which the amount of the phenol-rich phase (B) continually increases

•At the same time the amount of the water-rich phase (A) decreases.

Once the total conc. of phenol exceeds 63 % at 50 0C a single phenol-rich liquid phase is
formed

•The line bc drawn across the region containing two phases is termed a tie line; it is always
parallel to the base line in two component systems.
•all systems prepared on a tie line at 50° C will separate into phases of constant composition
whose composition is b and c. These phases are termed conjugate phases. 

The critical solution temperature (upper consolute temperature): Is the maximum temperature
at which the two phase region exists. In the case of the phenol-water system this is 66.8°

•All combinations of phenol and water above this temperature are completely miscible and
yield one-phase liquid systems 

Nicotine-Water System

•Mixtures such as nicotine & water show both an upper and a lower consolute temperature

•with an intermediate temperature region in which the two liquids are only partially miscible.

Systems with no critical solution temperature

•The pair, ethyl ether and water, has neither an upper nor a lower consolute temperature and
shows partial miscibility over the entire temperature range at which the mixture exists.

Triethylamine-Water System

•The solubility of liquid pairs may increase as the temperature is lowered

•The system will exhibit a lower consolute temp.

•Below which the two members are soluble in all proportions

•Above which two separate layers are formed.

Lecture 7 & 8 Fractional Distillation and

Azeotropes
Fractional Distillation

Fractional distillation is a type of distillation which involves the separation of miscible

liquids. The process involves repeated distillations and condensations and the mixture is
usually separated into component parts. The separation happens when the mixture is heated at
a certain temperature where fractions of the mixture start to vaporize.

The basic principle of this type of distillation is that different liquids boil and evaporate at
different temperatures. So when the mixture is heated, the substance with lower boiling point
starts to boil first and convert into vapours.

Principle

When a liquid mixture is distilled, the partial condensation of the vapour is allowed to occur
in a fractionating column. In the column, ascending vapour from the still is allowed to come
in contact with the condensing vapour returning to the still. This results in the enrichment of
 the vapour with more volatile component. By condensing the vapour and reheating the liquid
repeatedly, equilibrium between liquid and vapour is set up at each stage, which ultimately
results in the separation of a more volatile component.

Procedure

Few fractional distillation apparatuses are required for the process. It includes distilling flask,
condenser, receiver, fractionating column, thermometer and heat source.

After setting up the apparatus, a mixture of two miscible liquids A and B is taken where A has more
volatility than substance B. The solution is added into the distilling flask while the fractionating column is
connected at the tip of the flask. Heat is applied which increases the temperature slowly. The mixture then
starts to boil and vapours start rising in the flask. The vapours are from the volatile component A. The
vapours then start moving through the fractionating column into the condenser where it is cooled down to
form a liquid which is collected in the receiver.

Throughout the process, vaporisation and condensation take place repeatedly until the two mixtures are
separated completely.

Applications of Fractional Distillation 

 Fractional distillation is used for the purification of water as well as separating acetone and water.
 Fractional distillation is used in several industries like oil refineries and chemical plants mainly for
purification and separation of many organic compounds.
 Fractional distillation is also used for the separation of (liquefied) air. Components like liquid
nitrogen and oxygen as well as concentrated argon are obtained.
 Distillation is used in the production of high-purity silicones from chlorosilanes. The silicon is
widely used in semiconductors.

Azeotropic Mixture:

An azeotropic mixture is a mixture of substances that has the same concentration of vapour and fluid
phases. It is basically a mixture that contains two or more liquids.

Azeotropic mixture basically has constant or same boiling points and the mixtures’ vapour will also have
the same composition as the liquid.

Normally, we use distillation to isolate materials as the ideal solutions with one part normally more volatile
than the other. However, in an azeotropic mixture, since the vapour and fluid concentrations will be the
same and this approach will prevent their separation.

Two, three and more azeotropes can be either uniform or heterogeneous (more than a phase). Azeotrope
usually happens when a mixture is heated in order to produce vapour with the same liquid composition.

Meanwhile, the term azeotrope has been adopted from Greek words ζέειν meaning “boil” and τρόπος
meaning “turning” with the prefix α- (no). This translates to “no change on boiling”. English chemists John
Wade and Richard William Merriman used the term for the first time in the year 1911.

If the mixture deviates from Raoult's Law then azeotropes are formed and for azeotropes bubble point and
dewpoints is same. Mixtures of non-azeotropic liquids under any circumstances are referred to as
zeotropic.

 
 Azeotrope Mixture Types

There are different types of azeotropic mixtures:

1) Minimum Boiling Azeotropes or Negative Azeotrope

Azeotropic mixtures with less boiling point are called negative azeotropes in their constitutions. Water
boils at hundred degrees Celsius and hydrochloric acid boil at about minus eight degrees Celsius, while
azeotropes boil at around seventy-eight degrees Celsius indicating a boiling point greater than its
constituents. Consider, for example, a negative azeotropic hydrochloric acid consisting of a weight
concentration of approximately twenty per cent and 79 per cent of water.

Examples:

 Separation of water and isobutanol.

 Dehydration of ethanol.
 Separation of cyclohexane and benzene.

2.  Maximum Boiling Azeotropes or Positive Azeotrope

Similarly, an azeotropic mixture that has a boiling point higher than its constituents is known as positive
azeotropes. Consider, for example, a positive azeotrope, ethanol consisting of a weight concentration of
approximately ninety-five per cent and four per cent of water. Water boils at one hundred degrees Celsius,
and ethanol boils at about seventy-eight degrees Celsius, while azeotropes boil at around seventy-eight
degrees Celsius, suggesting a boiling point lower than its constituents.

Examples:

 Nitric Acid (HNO3) (68%) and water (32%) form maximum boiling azeotrope at boiling
temperature of 393.5 K
 Hydrochloric Acid (HCl) (20.24%) and water form maximum boiling azeotrope at boiling
temperature of 373 K

Azeotropes Examples

Boiling a 95% solution of ethanol in water will produce a 95% ethanol vapour. It is not necessary to use
distillation to obtain higher ethanol concentrations. Alcohol and water are miscible, making it possible to
combine any quantity of ethanol with any quantity to produce a homogeneous solution that works like an
azeotrope.

On the other side, chloroform and water make up a hetero-azeotrope. These two liquids are separated by a
mix which comes mainly from the top layer of the water, with a small amount of chloroform being
dissolved and a small amount of water dissolved from the chloroform base layer. The mixture can be
streamed at a lower temperature when the two layers are heated together as the boiling water or
chloroform. The resultant vapour would be 97% chloroform and 3% water, irrespective of the liquid ratio.
The condensation of vapours contributes to fixed layers of composition. The upper layer comprises 4.4 per
cent of thickness, while the lower condensate layer contains 95.6 per cent.

Lecture 9 Distribution Law

 Distribution Law

This Law was given by Nernst. This law gives the relationship between the concentration of a given
substance in two different phases in equilibrium with each other.

Suppose, if a small quantity of solute soluble in both the liquids is added then solute distributes it self in
two liquid & equilibrium is set up. Both the liquids must be immiscible with each other If the
concentration of the solute in two liquids are C1 & C2. According to this law,

C1/C2=K (constt.)

k= distribution coefficient

Let us consider two immiscible liquids X and Y in a separating funnel.

Solute Z is then added to the separating funnel containing X and Y. The separating funnel is then shaken
so that the solute Z dissolves in both X and Y. The resulting two immiscible solutions are then allowed to
settle until dynamic equilibrium is reached. The next question that comes to mind is this: how much of Z
has dissolved in liquid X, and how much of Z has dissolved in liquid Y?

When the distribution of the solute X has reached dynamic equilibrium, the rate (R1) at
which molecules of X pass from solvent A to B is proportional to its concentration (C1) in A.
The rate (R2) at which molecules of X pass from solvent B to A is proportional to its
concentration (C2) in B. Also, at equilibrium, the rate of migration of solute from one solvent
to the other is equal.

Thus we have,

R1 ∝ C1

or R1 = k1 × C1 where k1 is a constant

Again R2 ∝ C2

or R2 = k2 × C2 where k2 is a constant

Since at equilibrium R1 = R2

k1 × C1 = k2 × C2

C1/C2=kI/k2=KD

This is the Nernst’s Distribution law equation. Since k1 and k2 are constants

Factors affecting Distribution Coefficient-

1. The value of K depends upon the temperature , nature of solute , nature of two solvents .
2. It does not depend upon the amount of solute or solvents taken.

If the solubilities of given solute in the two solvents at the given temperature are S  & 1

S  respectively, then
2
 C /C  = S /S  =K
1 2 1 2

Example: Water & ether are immiscible with each other. Solute succinic acid is soluble in
both of these solvents. If small amount of succinic acid is added in a mixture . Then,

Concentration of succinic acid in water = C water

Concentration of succinic acid in ether = C ether

K = C water /  Cether

C   is more than C  so C   is taken in the numerator & C   in the denominator.
water  ether water ether

Experimental Verification

For experimental verification of distribution law, different quantity of the solute are added in
different quantities of two solvents in many experiments . If the value of distribution
coefficient for each experiment remains the same. This shows that the data follows
distribution law.

Conditions for Distribution Law

1. Both the solvents must be immiscible with each other

2. It is applicable only for dilute solution
3. Temperature remains constant throughout the experiment.
4. The molecular state of the solute in the two solvents should be the same.

Applications of Distribution Law

1. Determination of Solubility The values of K is equal to the ratio of solubilities of the solute
in the two solvents.

        K =C / C  = S / S 1 2 1 2

     If value of K & solubility of the solute in one solvent is known then we can calculate the
solubility of solute in other solvent.

1. Solvent Extraction. Extraction of one substance from a solution containing various

substances by using a suitable solvent is known as solvent extraction.

“The amount of extracted substance is more if smaller amount of solvent are used many times
rather than using larger amount of solvent a fewer times”.

Limitations of Distribution Law

The conditions to be satisfied for the application of the Nernst’s Distribution law are :

1. Constant temperature. The temperature is kept constant throughout the experiment.

 2. Same molecular state. The molecular state of the solute is the same in the two solvents.
The

law does not hold if there is association or dissociation of the solute in one of the solvents.

3. Equilibrium concentrations. The concentrations of the solute are noted after the
equilibrium

has been established.

4. Dilute solutions. The concentration of the solute in the two solvents is low. The law does

not hold when the concentrations are high.

5. Non-miscibility of solvents. The two solvents are non-miscible or only slightly soluble in

each other. The extent of mutual solubility of the solvents remains unaltered by the addition

of solute to them.

States of matter
LECTURE 10
Key Points
 Matter can exist in one of three main states: solid, liquid, or gas.
 Solid matter is composed of tightly packed particles. A solid will retain its shape; the
particles are not free to move around.
 Liquid matter is made of more loosely packed particles. It will take the shape of its
container. Particles can move about within a liquid, but they are packed densely enough that
volume is maintained.
 Gaseous matter is composed of particles packed so loosely that it has neither a defined
shape nor a defined volume. A gas can be compressed.
 Terminology:
 Solid: A substance that retains its size and shape without a container; a substance
whose molecules cannot move freely except to vibrate.
 Gas: A substance that can only be contained if it is fully surrounded by a container (or
held together by gravitational pull); a substance whose molecules have negligible intermolecular
interactions and can move freely.
 Liquid: A substance that flows and keeps no definite shape because its molecules are
loosely packed and constantly moving. It takes the shape of its container but maintains constant
volume.

The three states of matter are the three distinct physical forms that matter can take in most
environments: solid, liquid, and gas. In extreme environments, other states may be present, such
as plasma, Bose-Einstein condensates, and neutron stars. Further states, such as quark-gluon
plasmas, are also believed to be possible. Much of the atomic matter of the universe is hot
plasma in the form of rarefied interstellar medium and dense stars.

Historically, the states of matter were distinguished based on qualitative differences in their bulk
properties. Solid is the state in which matter maintains a fixed volume and shape; liquid is the
state in which matter adapts to the shape of its container but varies only slightly in volume; and
gas is the state in which matter expands to occupy the volume and shape of its container. Each
of these three classical states of matter can transition directly into either of the other two classical
states.

Solids

A solid’s particles are packed closely together. The forces between the particles are strong
enough that the particles cannot move freely; they can only vibrate. As a result, a solid has a
stable, definite shape and a definite volume. Solids can only change shape under force, as when
broken or cut.

In crystalline solids, particles are packed in a regularly ordered, repeating pattern. There are
many different crystal structures, and the same substance can have more than one structure. For
example, iron has a body-centered cubic structure at temperatures below 912 °C and a face-
centered cubic structure between 912 and 1394 °C. Ice has fifteen known crystal structures,
each of which exists at a different temperature and pressure.

A solid can transform into a liquid through melting, and a liquid can transform into a solid through
freezing. A solid can also change directly into a gas through a process called sublimation.

Solids can exist as crystalline, amorphous, solvate (hydrate), and desolvated (dehydrated)
forms. Crystals exist with the molecules arranged in a repeating pattern with an identifiable
symmetry. However, there can be more than one possible repeating pattern for many drugs.
This can be demonstrated by visualizing a number of identical Lego pieces of a specific
shape.
 Polymorphism

Polymorphism is quite common for the same material to crystallize in different (more than
one) arrangement of molecules in crystal. Polymorphism can be classified into two types
according to their stability with respect to the different range of temperature and pressure.

Monotropic System

Only one polymorph is stable at all reasonable temperatures. e.g. metolazone

Enantiotropic system

One polymorph is stable over one temperature range, another polymorph is stable over a
different temperature range – e.g. carbamazepine and acetazolamide.

Relationship between Polymorphs and Solvates

 Thermodynamically most stable anhydrous form may no longer be most stable: will
convert to solvate in the present of the right amount of the solvent.
 The thermodynamically most stable solvate is not necessarily associated with the
lowest degree of solvate.
 A particular solvate may have polymorphs.e.g. Nedocromil Zinc

Important Points about Polymorphs

 Pharmaceutical solids may be crystals, crystal solvates or hydrates, crystal desolvated

solvates or dehydrated hydrates, or amorphous solids
 All crystal forms described can exist in different forms called polymorphs
 Polymorphs can have significant differences in their physical properties even though
they are chemically identical. Physical properties include solubility, melting point, particle
size, dissolution rate, hygroscopicity, and others.
 Polymorphs may interconvert depending on conditions. Usually the metastable kinetic
form converts to the stable thermodynamic form.
 Laboratory studies are key to determining the potential of a compound to form
multiple polymorphs, determining under what conditions the polymorphs are formed, what
are the physical properties of each polymorph, and what is the stability of each polymorph
 The primary analytical method to characterize polymorphs is x-ray diffraction. Other
methods used include solid state NMR, Raman and NIR spectroscopy, and thermal methods
such as DSC and TGA.
 Seeding is used to facilitate manufacturing of the desired polymorph

Lecture 11 & 12 Gas and Liquid State

A solid has definite volume and shape, a liquid has a definite volume but no definite
shape, and a gas has neither a definite volume nor shape.

The Gaseous State

(i) Gases have no definite volume and they do not have specific shape,

(ii) Gases mix evenly and completely in all proportions without any mechanical aid.

(iii) Their density is much lower than solids and liquids.

(iv) They are highly compressible and exert pressure equally in all direction

Boyle’s Law (Pressure-Volume Relationship)

At constant temperature, the volume of a given mass of gas is inversely proportional to its
pressure.
Charles’ law: 

At constant pressure, the volume of a given mass of a gas is directly proportional to its
absolute temperature.

Gay Lussac’s Law (Pressure-Temperature Relationship)

At constant volume, pressure of a given mass of a gas is directly proportional to the

temperature.
Ideal Gas: A gas that follows Boyle’s law, Charles’ law and Avogadro law strictly, is called
an ideal gas.

Real gases follow these laws only under certain specific conditions. When forces of
interaction are practically negligible.

Ideal Gas Equation

This is the combined gas equation of three laws and is known as ideal gas equation.

Dalton’s Law of Partial Pressure

When two or more non-reactive gases are enclosed in a vessel, the total pressure exerted by
the gaseous mixture is equal to the sum of the partial pressure of individual gases.
Let P1 ,P2, and P3 be the pressure of three non reactive gases A, B, and C. When enclosed
separately in the same volume and under same condition.

P  = P1+ P2 + P3
Total

Where, P  = P is the total pressure exerted by the mixture of gases.

Total

Partial Pressure in terms of Mole Fraction

Let at the temperature T, three gases enclosed in the volume V, exert partial pressure P1 ,
P2 and P3 respectively, then

Kinetic Molecular Theory of Gases

(i) Gases consist of large number of very small identical particles (atoms or molecules),

(ii) Actual volume occupied by the gas molecule is negligible in comparison to empty space
between them.

(iii) Gases can occupy all the space available to them. This means they do not have any force
of attraction between their particles.

(iv) Particles of a gas are always in constant random motion.

(v) When the particles of a gas are in random motion, pressure is exerted by the gas due to
collision of the particles with the walls of the container.
 (vi) Collision of the gas molecules are perfectly elastic. This means there is no loss of energy
after collision. There may be only exchange of energy between colliding molecules.

(vii) At a particular temperature distribution of speed between gaseous particles remains

constant.

(viii) Average kinetic energy of the gaseous molecule is directly proportional to the absolute
temperature.

Liquid State
 A liquid is a fluid that conforms to the shape of its container but that retains a nearly constant
volume independent of pressure.
 The volume is definite (does not change) if the temperature and pressure are constant.
 When a solid is heated above its melting point, it becomes liquid because the pressure is
higher than the triple point of the substance.
 Intermolecular (or interatomic or interionic) forces are still important, but the molecules have
enough energy to move around, which makes the structure mobile. This means that a liquid is not
definite in shape but rather conforms to the shape of its container. Its volume is usually greater than
that of its corresponding solid (water is a well-known exception to this rule). The highest temperature
at which a particular liquid can exist is called its critical temperature.
 A liquid can be converted to a gas through heating at constant pressure to the substance’s
boiling point or through reduction of pressure at constant temperature. This process of a liquid
changing to a gas is called evaporation.

Liquid Crystals

In a normal liquid, the molecules possess enough thermal energy to overcome the
intermolecular attractive forces and tumble freely. This arrangement of the molecules is
described as isotropic, which means that it is equally disordered in all directions. Liquid
crystals, in contrast, are anisotropic: their properties depend on the direction in which they are
viewed. Hence liquid crystals are not as disordered as a liquid because the molecules have
some degree of alignment.

Most substances that exhibit the properties of liquid crystals consist of long, rigid rod- or
disk-shaped molecules that are easily polarizable and can orient themselves in one of three
different ways:

 In the nematic phase, the molecules are not layered but are pointed in the same direction. As a
result, the molecules are free to rotate or slide past one another. I
 n the smectic phase, the molecules maintain the general order of the nematic phase but are
also aligned in layers. Several variants of the smectic phase are known, depending on the angle
formed between the molecular axes and the planes of molecules. The simplest such structure is the so-
called smectic A phase, in which the molecules can rotate about their long axes within a given plane,
but they cannot readily slide past one another.
 In the cholesteric phase, the molecules are directionally oriented and stacked in a helical
pattern, with each layer rotated at a slight angle to the ones above and below it. As the degree of
molecular ordering increases from the nematic phase to the cholesteric phase, the liquid becomes
more opaque, although direct comparisons are somewhat difficult because most compounds form only
one of these liquid crystal phases when the solid is melted or the liquid is cooled.
 Because of their anisotropic structures, liquid
crystals exhibit unusual optical and electrical
properties. The intermolecular forces are rather weak
and can be perturbed by an applied electric field.
Because the molecules are polar, they interact with
an electric field, which causes them to change their
orientation slightly.

Nematic liquid crystals, for example, tend to be

relatively translucent, but many of them become
opaque when an electric field is applied and the
molecular orientation changes. This behavior is ideal
for producing dark images on a light or an opalescent background, and it is used in the LCDs
in digital watches; handheld calculators; flat-screen monitors; and car, ship, and aircraft
instrumentation.

Lecture 13 Phase Rule

Lecture 13 Phase Rule
Terminology
1) Phase: A phase is defined as “an homogeneous, physically distinct and mechanically
separable portion of system, which is separated from other such parts of the system by
definite boundary surface”.
For Example:
1. At freezing point, water consists of three phase :

       Ice (s)   Water (l)  Water vapour (g)

1. A gaseous mixture, being thoroughly miscible in all proportion, will constitute one phase
only. Thus, a mixture of N2 and H2 forms phase only.
2. If two liquids are immiscible (i.e., benzene and water), they will form two separate phase
only.
3. If two liquids are miscible (i.e., alcohol and water), they will form one liquid phase only.
4. A solution of a substance in a solvent consists of phase only, e. g, glucose solution in
water.
5. Each solid mark up a separate phase, except in the case of solid solution, e. g, many
forms of sulphur can exist together, but these are all separate phases.
6. A heterogeneous mixture like :

        CaCO3 (s)   CaO(s) + CO2 (g)

Consists of three phases  (i.e., two solids and one gasous). Similarly, in the equilibrium reaction,

Fe(s) + H2O    FeO(s) + H2(g)

There are two solid phases, Fe and FeO and one gaseous phase consisting of H2O(g) and H2(g).
Thus, three phases exists in equilibrium.                                                   
A homogeneous solid solution of a salt constitutes a single phase. Thus, Mohr’s
[ FeSO4 (NH4)2SO46H2O] solution constitutes a single phase, although it consists of FeSO 4 (NH4)
SO4, and H2O.

2) Component: is meant “the smallest number of independent variable constituents, taking part
in state of equilibrium, by mean of which the composition of each phase can be expressed in the
form of chemical equation”. For example:

        i.           In the water system,

                                   Ice (s)  Water (l)  vapour (g)

The chemical composition of all the three phases is H2O. Hence, it is one component system.

      ii.           the sulphur system consists of four phases, rhombic, monoclinic, liquid and vapour,
the chemical composition of all phases is S. hence, it is one component system.

3) Degree of freedom or variance: By the term “degree of freedom is meant by” the minimum
number of independently variable factors, such as temperature, pressure and composition of the
phases, which must be arbitrarily specified in order to represent perfectly the condition of a
system. For example

        i.           In case of water system, Ice(s )      Water(l)      Vapour(g), if all the three
phases are present in equilibrium, then no condition need to be specified, as the three phases
can be in equilibrium only at particular temperature and pressure. If condition (e.g. Temperature
or pressure is altered, three phases will not remain in equilibrium and one of the phase
disappears.

       ii.           For a system consisting of water n in contact with its vapour,

                                                      Water(l)       Vapour(g)

We must state either the temperature or pressure to define it completely. Hence, degree of
freedom is one or system is univariant.

     iii.           For a system consisting of water vapour phase only, we must the values of both the
temperature and pressure in order to describe the system completely. Hence, the system is
bivariant or has two degrees of freedom.

Phase Rule

It states that : When the equillibrium between any number of phases is influenced only by
temperature, pressure and concentration but not influenced by gravity, or elctrical or magnetic
forces or by surface action then the number of Degrees of Freedom (F) of the system is related
to the number of Components (C) and of Phases (P) by the phase rule equation:

F+P=C+2
Merits of phases rule:

 1. It is applicable to both physical and chemical equilibria.

 2. It require no information regarding molecular/ micro-structure, since it is applicable to 

    macroscopic system.

 3. It is a convenient method of classifying equilibrium states in terms of phases, components   

   and degrees of freedom.

 4. It helps us to predict the behaviour of a system, under different sets of variables.

 5. It indicates that different systems with same degree of freedom behave similarly.

 6. It does not take into cognizance of either the nature or quantities of component present in

   the system.

Limitation of Phase Rule:

1. It can be applied only for system in equilibrium. Consequently, consequently, it is of little value
in case of very slow equilibrium state attaining system.

2. It applies only to a single equilibrium system: and provided no information regarding any other
possible equilibria in the system.

3. It requires utmost care in deciding the number of phases existing in an equilibrium sate, since
it considers only the number of phases, rather than their amounts. Thus, even if a trace of the
phase is present, it accounts towards the total number of phases.

4. It conditions that all phases of the system must be present simultaneously, under the identical
conditions of temperature and pressure.

5. It conditions that solid and liquid phases must not be in finely –divided state; otherwise
deviations occurs.

Water System (One Component System)

            The water system consists of three phases , viz., ice, water and water vapour.

                             Ice(s)         Water (I)       Water vapour (g)

 
 Since H2O is the only chemical compound involved, therefore, it is single or one-component
system . From the phase rule, when C =1,

                                F = C – P + 2 =1 – P + 2 = 3 – P

i.e, the degree of freedom depends on the number of phases present at equilibrium. Three
different case are possible :

               (i) P = 1 ;     F = 2                                          (bivariant system)

               (ii) P = 2 ;     F = 1                                          (univariant system)

               (iii) P = 3 ;    F = 0                                         (invariant system)

From the above , it is clear that for any one-component system , the maximum number of
degrees of freedom is two. Therefore, such a system can be represented completely by a two-
dimensional Diagram. The most convenient variable are the pressure and the temperature. The
water system is shown in Fig.

1. The curve OA, dividing the liquid from the vapour region, is called vapour pressure
curve of liquid water or vaporization curve. At any given temperature, there is one and only
one pressure at which water vapour is in equilibrium with liquid water. Similarly , at any
given pressure, there is one temperature at which water vapour is in equilibrium with liquid
 water. In other words, the system is univariant. i.e,, has one degree of freedom. The curve OA
has a natural upper limit at +374 C. which is the critical-point, beyond which the phase
merges into vapour phase and they are no longer distinguishable from each other.
2. The curve OB is the sublimation curve of ice. It gives the conditions under which
water vapour is in equilibrium with solid ice. The point B has a natural limit at -273 C,
o

beyond which the two phases merge into each other.

3. The curve OC , which divies the solid –ice region from the liquid – water region, is
called melting curve, because it indicates how the melting temperature of ice or the freezing
tempereature of water varies with the pressure. The slope of OC towards the pressure axis
shows that the melting point of ice is decreased by increasing pressure.

Triple point:    The three curves OA, OB, and OC meet at O, at which solid, liquid and
vapour are simultaneously at equilibrium. This point at 273.16 k is called a triple –
point
Lecture 14 Drug Dissolution
Dissolution

Dissolution is defined as the process in which a solid substance solubilizes in a given solvent
i.e. mass transfer from the solid surface to the liquid phase.
 Drug Release
1. Immediate release drug products allow drugs to dissolve with no intention of delaying or
prolonging dissolution or absorption of the drug
2. Delayed release is defined as the release of a drug at a time other than immediately following
administration.
3. Enteric Coated: Intended to delay the release of the drug (or drugs) until the dosage form has
passed through the stomach. Enteric-coated products are delayed-release dosage forms.
4. Targeted release drug release directed toward isolating or concentrating a drug in a body
region, tissue or site of absorption or for drug action
5. Extended-release products are formulated to make the drug available over an extended period
after administration.
6. Prolonged-release dosage forms are modified-release dosage forms showing a slower release
of the active substance(s) than that of a conventional-release dosage form administered by the same
route. Equivalent term: extended-release dosage form.
7. Modified-Release Dosage Forms: Dosage forms whose drug-release characteristics of time
course and/or location are chosen to accomplish therapeutic or convenience objectives not offered by
conventional dosage forms such as a solution or an immediate- release dosage form OR Modified-
release dosage forms are preparations where the rate and/or place of release of the active substance(s)
is different from that of a conventional- release dosage form administered by the same route.
 Dissolution Test

This test measures the amount of time required for a given percentage of the drug substance
in a tablet to go into solution under a specified set of conditions. It is intended to provide a
step toward the evaluation of the physiological availability of the drug substances.

In vitro dissolution test is performed using a variety of equipment/apparatus. The British

Pharmacopoeia recommends three types of apparatus – the rotating basket, the rotating
paddle and the flow-through cell. The static-basket magnetic stirrer assembly can also be
used for this test.

The rotating paddle method is generally more discriminatory than the basket method. The
flow-through cell method is very useful particularly for

1. Poorly soluble active constituents (can use large volume to achieve sink conditions)
2. Enteric-coated products (can easily change between different pH fluids)
3. Modified release products.

The dissolution medium for each drug is available in the individual drug monograph. For
basic drugs, acidic media are used (e.g. 0.1 M hydrochloric acid) while alkaline media are
used for acidic drugs (e.g. alkaline buffers). For drugs with non-ionizing molecules, water is
recommended.

Dissolution rate test is performed at 37 ± 1  C. Samples are removed from the dissolution
o

chamber at periodic intervals and analyzed for drug content using a spectrophotometer.
Dissolution samples removed for assay should be filtered to remove particles of drugs
present, and to exclude tablet excipients that might otherwise interfere with the assay. Non-
absorbent filter papers are recommended.
Most commonly, the results of dissolution tests are expressed in terms of the time required to
release some percentage of labelled amount of drug from the dosage form. This approach is
reported to be particularly useful for quality control purposes once the dissolution
characteristics of a drug and dosage form are well understood.

For tablet dosage form design purposes, and for critical product comparison, however, the
time required for substantially complete 80 to 90% release or amount released versus time
profiles are the most desired approach.

At the interface, the packet is able to absorb solute according to the laws of diffusion and is
then replaced by a new packet of solvent. This surface renewal process is related to the solute
transport rate and hence to the dissolution rate.

The rate laws predicted by the different mechanisms both alone and in combination, have
been discussed by Higuchi . However, the earliest equation expressing dissolution rate in a
quantitative manner was proposed by Noyes and Whitney  as:-

dc / dt = k (C s - C t )

where

dc / dt is the rate of change in concentration with respect to time, and k is the rate constant.
 The integrated form of the equation is:

In [C s / (C s - C t ) ] = kt

The equation in resemblance to the other rate law equations , predicts a first order
dependence on the concentration gradient (i.e. C s - C t ) between the static liquid layer next
to the solid surface and the bulk liquid. Noyes and Whitney explained their dissolution data
using a concept similar to that used for the diffusion model. This considerations relate to
conditions in which there is no change in the shape of the solid during the dissolution process
(i.e. the surface area remains constant). However, for pharmaceutical tablets, disintegration
occurs during the dissolution process and the surface area generated therefore varies with
time.

Lecture 15 & 16 Drug Release Controlled

Systems
Lecture 15 & 16 Drug Release
Controlled Systems
Controlled release dosage form is a dosage form that release one or more drugs continuously in
predetermined pattern for a fixed period of time, either systemically or locally to specified target
organ. Greater attention is paid on development of oral controlled release drug delivery systems
due to flexibility in designing of dosage form. The main challenges to oral drug delivery systems
are to deliver a drug at therapeutically effective rate to desirable site, modulation of GI transit
time and minimization of first pass elimination. Control release dosage form provides better
maintenance of optimal and effective drug level for prolonged duration with less dosing frequency
and side effects

The modified release oral drug delivery systems classified as are:

1. Controlled release-
2. - Sustained release
3. - Extended release
4. - Prolonged release
1) Dissolution controlled release

Dissolution is defined as solid substance solubilized in a given solvent. It is a rate determining

step when liquid is diffusing from solid. Several theories explain dissolution: Diffusion layer
theory, Surface renewal theory, Limited solvation theory. 

Noyes Whitney Equation

dc/dt = kD.A (Cs – C)

dc/dt = D/h A. (Cs – C)

dc/dt = Dissolution rate, k= Dissolution rate constant (1st order), D = Diffusion

coefficient/diffusivity, Cs = Saturation/ maximum drug solubility, C =Conc. Of drug in bulk
solution, Cs-C=concentration gradient, h =Thickness of diffusion layer.
Two common formulation system rely on dissolution to determine release rate of drugs are:

(i) Encapsulated dissolution system (ii) Matrix dissolution system

(i) Encapsulated dissolution system

This is also known as Coating dissolution controlled system. Dissolution rate of coat depends
upon stability & thickness of coating. It masks color, odor, taste and minimize GI irritation.
Controlled release products by decreasing the dissolution rate of drugs which are highly water
soluble can be formulated by preparing appropriate salt or derivatives, by coating the drug with a
slowly dissolving material, or by incorporating the drug into a slowly dissolving carrier. Examples:
Ornade spansules, Chlortrimeto Repetabs.

(ii) Matrix dissolution system

It is also known as monolithic dissolution controlled system. In this dissolution IS controlled by:
Altering porosity of tablet, decreasing its wet ability, dissolving at slower rate. It follows first order
drug release. The drug release can be determined by dissolution rate of polymer. Examples:
Demeaned extencaps, Dimetapp extentabs.

2) Diffusion controlled system

It is a major process for absorption in which no energy required.In this drug molecules diffuse
from a region of higher concentration to lower concentration until equilibrium is attained and it is
directly proportional to the concentration gradient across the membrane. In this system release
rate is determined by its diffusion through a water-insoluble polymer. There are two types of
diffusion devices:

(i) Reservoir diffusion system

(ii) Matrix diffusion system

(i) Reservoir diffusion system

It is also called as laminated matrix device. It is a hollow system containing an inner core
surrounded by water insoluble membrane and polymer can be applied by coating or micro
encapsulation. The Rate controlling mechanism is that drug will partition into membrane and
exchange with the fluid surrounding the drug by diffusion. Commonly used polymers are HPC,
ethyl cellulose & polyvinyl acetate. Examples: Nico-400, Nitro-Bid.

Rate controlling steps: Polymeric content in coating, thickness of coating, hardness of

microcapsule.

(ii) Matrix Diffusion system

(a) Rigid Matrix Diffusion: Materials used are insoluble plastics such as PVP & fatty acids.

(b) Swellable Matrix Diffusion: it is also called as Glassy hydro gels and popular for sustaining
the release of highly water soluble drugs. Materials used are hydrophilic gums19. Examples:

Natural- Guar gum, Tragacanth.

Semi synthetic -HPMC, CMC, Xanthum gum.

Synthetic -Polyacrilamides.

Examples: Glucotrol XL, Procardia XL

3) Dissolution & Diffusion Controlled Release system

In this drug is encased in a partially soluble membrane and pores are created due to dissolution
of parts of membrane.It permits entry of aqueous medium into core & drug is dissolved or
diffused out of the system. Ex- Ethyl cellulose & PVP mixture dissolves in water & creates pores
of insoluble ethyl cellulose

4) Osmotically controlled release system

Osmosis is defined as themovement of solvent from lower to higher concentration through

semi permeable membrane. Osmotic pressure is the hydrostatic pressure produced by a
solution in a space divided by a semi permeable membrane due to difference in concentration
of solutes. This technology provides zero order release used for hydrophilic drugs. Drug may
be osmotically active, or combined with an osmotically active salt (e.g., NaCl). Semi
permeable membrane is usually made from cellulose acetate. Examples: Glucotrol XL,
Procardia XL.

The volume flow of water into core reservoir dv/dt is expressed as:

dv/dt = K A/ h (Δπ-Δp)

K, A & h= Membrane permeability, effective surface, area & thickness of semi permeable
membrane, Δπ= osmotic pressure difference, Δp= hydrostatic pressure difference.