States OF Matter

PhysicalPharmacy1(P221PT)
Department of Pharmaceutics
Lecture 2
2023-2024
By: Dr. Nabila A. Rghebi
• Matter is anything that takes up space & has mass.
• The most basic classification scheme of matter is based on the states of:
Solid Liquid Gas

 Basis of Classification of the Three Types of state:

• Based upon particle arrangement.
• Based upon energy of particles.
• Based upon distance between particles.

 The state of matter can be altered by adding or removing energy

and/or pressure which can affect the arrangement and energy of the
particle.
 Solid Liquid Gas

Particles of solids are Particles of liquids are Particles of gases are

tightly packed, vibrating tightly packed, but are very far apart and move
about a fixed position. far enough apart to slide freely.
over oneanother.

Solids have a definite Liquids have an Gases have an indefinite

shape and a definite indefinite shape and a shape and an indefinite
volume. definite volume. volume.
 PHASE CHANGES:

A change of state or phase transition is a change of a substance from one state

to another.

• Melting/Freezing.
• Boiling(vaporization)/Condensing.
• Sublimation/Deposition.
• Evaporation.

1- Melting/Freezing:
• Change from solid to liquid and liquid to solid.
• Same temp.; if melting, particles are gaining energy; if freezing, particles
are losing energy.

The stronger the IF’s, the more energy needed to weaken the IF’s,
therefore higher melting point temperature.
2- Boiling (vaporization)/Condensing:
• Change from liquid to gas and gas to liquid.
• Same temp.; if boiling, particles are gaining energy; if condensing, particles
are losing energy.

The stronger the IF’s, the more energy needed to break the IF’s, therefore
higher boiling point temperature.

3- Sublimation:
• Changing directly from a solid to a gas.

4- Deposition:
• Changing directly from a gas to a solid.

4- Evaporation:
• Liquid to gas but not necessarily at the boiling point temperature.
• Some particles gain enough K.E. to overcome the IF’s and become a gas.
PHASE DIAGRAMS: (Temperature vs. Pressure)
Heating curve for 1gram of water
 1- THE GASEOUS STATE

As the temperature of a solid substance is raised the particles

acquire sufficient energy to disrupt the ordered arrangement of
the lattice and pass into the liquid form. Finally, when sufficient
energy is supplied the molecules pass into the gaseous state.
Properties of gases:
1- Gases can be expanded infinitively, therefore gases can fill
containers and take their volume and shape.
2- Gases diffuse and mix evenly and rapidly.
3- Gases have much lower densities than liquids and solids
(There is a lot of free space in a gas, therefore; It is the most
compressible state of matter).
4- Gas molecules travel in random paths and collide with one another
and with the walls of the container in which they are confined.

5- Gas exerts a pressure (a force per unit area) expressed in

dynes/cm2, atmospheres or in mmHg(1atm = 760mmHg=760 Torr).

6- Gases have volumes that are expressed in liters or cubic

centimeters (1cm3=1mL).

7- The temperature involved in the gas equations is expressed by

the absolute or Kelvin scale (0°C=273.15K(Kelvin)).
ºC = K - 273.15 K= C + 273.15
8- Gas molecules are characterized by:
a) No shape.
b) Weak or no intermolecular forces.
c) Low density.
d) High compressibility.
Diffusion:

Diffusion can take place in gases, liquids, or solids.

It is can be defined as the movement of particles from an area of high

concentration to an area of low concentration.

• Diffusion in gases is quick because the particles in a gas move quickly. It

happens even faster in hot gases because the particles of gas move faster.

• Diffusion in liquids is slower than diffusion in gases because the particles

in a liquid move more slowly. It happens faster if the temperature is
increased.

• Diffusion in solids is very, very slow.

• Diffusion happens more quickly at warm temperatures than at cooler

temperatures.
Effusion:

It is defined as the escape of gas molecules through a tiny opening.

The image on the left shows effusion, where the image on the right
shows diffusion.

Effusion occurs through an orifice smaller than the mean free path of the particles
in motion, whereas diffusion occurs through an opening in which multiple
particles can flow through simultaneously.
Compressibility:
Gases are higly compressible. This is due to the presence of large empty space
between the gas molecules. On applying pressure distance between the gas
molecules decrease, therefore, its volume decrease.

Mobility:
Gas can flow and can be transported through pipes over long distance but it can
also leak more rapidly out of small hole. This is due to the tendency of a gas to
expand and fill the entire available space.

Density:
The density of an object or substance is its mass divided by its volume:
density = mass ÷ volume
The units of density depend on the units used for mass and volume, but are usually:
g/cm3 (if mass is measured in g and volume in cm3).
Gases have lower density than other states of matter, such as solids and liquids.
This is because the molecules are much farther apart in the gas.
When a gas is cooled its density increases because its volume decreases.
Laws Related to Gases:

Gas can be characterized by four variables:

1- Pressure (P). (Atmospheres, atm)

2- Volume (V). (liters, L)
3- Tempreture (T). (Kelvin,K)
4- The number of moles of gas (n). (moles, mol)

The relationship that expresses the influence of one variable on another with the
two variable constant are called (gas laws).
 Real and Ideal gases
A real gas is a gaseous compound that really exists in the environment.
These real gases are composed of different atoms or molecules that are called
particles. These gas particles are in constant motion and has a definite
volume and mass.

An ideal gas is a hypothetical gas that does not really exist in the
environment. The concept of ideal gas was introduced since the behavior of
real gases are complicated and different from each other, and the behavior of
Ideal gases are gaseous compounds that are composed of very tiny molecules
that have a negligible volume and a mass.
 Ideal gas
Ideal gas:
Ideal gas is a gas where no intermolecular interactions exist and collisions are
perfectly elastic, and thus no energy is exchanged during collision.
The properties of the ideal gas can be described by the general ideal gas law,
which are derived from Boyle, Charles and Gay-Lussac laws.
The Ideal Gas Law:
1- Boyle's law:

This law states that the volume and pressure of a given mass of gas is inversely
proportional (i.e. when the pressure of a gas increases, its volume decreases).
P α 𝟏/𝑽 or P = 𝑲/𝑽 Or PV = K
P = pressure.
K= constant.
V = volume.
If a fixed amount of gas at constant temperature T occupying volume V1 at
pressure p1 undergoes expansion, so that volume becomes V2 and
pressure becomes p2,

then according to Boyle’s law: P1V1=P2V2

As the volume of the gas

decreases, the gas particles
have less room to move
around in, and they collide
more often with the walls of
the container, thus increasing
the pressure.
2- Gay-Lussac and Charles law:
The law of Gay-Lussac and Charles states that the volume and absolute
temperature of a given mass of gas at constant pressure are directly proportional.
(i.e when the temperature of a gas increases, its volume increases as well).
V α T or V = kT
𝑽𝟏/𝑻𝟏=𝑽𝟐/𝑻𝟐
V= volume.
K= constant.
T= temperature.
In this equation, temperature must be measured in the absolute (Kelvin) temperature scale.
Boyle, Gay-Lussac and Charles law can be combined to obtain the familiar
relationship:

𝑷𝟏𝑽𝟏/𝑻𝟏 = 𝑷𝟐𝑽𝟐/𝑻𝟐
P1 ,V1 , and T1 are the values under one set of conditions and P2, V2 , and T2 the
values under another set.

From this equation PV/T under one set of condition is equal to PV/T another
another set, and so on. Thus, one can conclude that although P, V, and T change, the
ratio PV/T is constant and can be expressed mathematically as:

or
in which R is the constant value for the PV/T ratio of an ideal gas. This equation is
correct only for 1 mole (i.e., 1 g molecular weight) of gas; for n moles it becomes:

Equation { PV=nRT} is known as the

P= pressure. General ideal law or the equation of state of
T= absolute temperature. an ideal gas and relates the specific
V= volume. conditions of pressure, volume, and
n= number of moles. temperature of given mass of gas.
R= molar gas constant
 Problems
EXAMPLE1:
A gas occupies a volume of 30.0 mL at a temperature of 20°C and a pressure of
740mmHg. Assuming the gas is ideal, what is the volume at 0°C and 760mmHg?
𝐏𝟏𝐕𝟏/𝐓𝟏 = 𝐏𝟐𝐕𝟐/𝐓𝟐
740×30/273+20 = 760×𝐕𝟐/273
𝐕𝟐 = 27.2mL

EXAMPLE2:
A sample of methane CH4 has a volume of 7.0 cm3 at a temperature of 4°C and a
pressure of 0.848 atm. Calculate the volume of methane at a temperature of 11°C
and a pressure of 1.52atm.
𝐏𝟏𝐕𝟏/𝐓𝟏=𝐏𝟐𝐕𝟐/𝐓𝟐
0.848×7/273+4 = 1.52×𝐕𝟐/273+11
𝐕𝟐 = 4cm3
The molar Gas constant(R):
To obtain a numerical value for R, let us proceed as follows. If 1 mole of an ideal
gas is chosen, its volume under standard conditions of temperature and pressure
(i.e.(STP) at 0°C and 760 mm Hg) has been found by experiment to be 22.414
liters).

The molar gas constant can also be given in energy units by expressing the pressure
in dynes/cm2 (1 atm = 1.0133 × 106 dynes/cm2) and the volume in the
corresponding units of cm3 (22.414 liters = 22,414 cm3). Then:

or, because 1 joule = 107 ergs,

The constant can also be expressed in cal/mole deg, employing the equivalent 1
cal = 4.184 joules:

where R is a proportionality constant called the ideal gas constant or universal

gas constant, which has the same value for all gases:
R = 0.08206 L atm K-1 mol-1
R = 8.3145 J K-1 mol-1
R = 8.3145 m3 Pa K-1 mol-1
R = 62.36 L torr K-1 mol-1
R = 1.9872 cal K-1 mol-1
Example
What is volume of 2 moles of ideal gas at 25 °C and 780 mmHg? ( 1 atm =760
mmHg and R = 0.08205 L • atm / (mol • K)

P= 780/760 = 1.026 atm

V= ?
n=2 mole
T= 25 °C+273= 298 k
PV= n R T
1.026 atm x V=2moles x 0.08205 L • atmmole.K x298K
V= 47.65 liter
Molecular weight:
The approximate molecular weight of gas can be determined by use of the ideal gas
law:
PV = nRT since n = g/M
(Where: g = number of grams of gas and M molecular weight)
Then:
PV = 𝐠/𝐌RT
M = 𝐠𝐑𝐓/𝐏𝐕

Methods for determination of molecular weight of gas:

The two methods most commonly used to determine the molecular weight of gas:
a) Regnault method.
b) Victor Meyer method.
Example
If 0.30g of ethyl alcohol in the vapor state occupies 200mL at a pressure of 1 atm
and a temperature of 100°C, what is the molecular weight of ethyl alcohol?
100°C+273 = 373K
200mL÷1000 = 0.2L
𝐌 = 𝐠𝐑𝐓/𝐏𝐕 = 0.3×0.082×373/1×0.2 = 46g/mole.
Kinetic Molecular Theory:
Matter is made up of particles which are in continual random motion.

Kinetic molecular theory explains the behavior of gases according to the

ideal gas law:

1-Gases are composed of particles called molecule, the total volume of

which is so small ( negligible ) in relation to the volume of the space in
which the molecules are confined.
2- Gas molecules exert neither attractive nor repulsive forces on one
another. (not to attract or to repel each other) ( NO
INTERMOLECULAR FORCES).

3- The particles are in constant random motion, colliding with the walls
of the container. These collisions with the walls cause the pressure
exerted by the gas.
 4-The average kinetic energy of the gas particles is directly
proportional to the absolute temperature of the gas. (i.e Kelvin temp).
temp.↑ → ↑ KE.

5- Experience elastic collisions in which no energy is lost.

NOTE:
 Kinetic energy = energy an object has due to its motion
 The faster an object is moving; the greater its kinetic energy.
 Kinetic theory states that all particles of matter are in constant
motion.
A quantitative relationship between pressure, volume, and the velocity of
molecules in gas:

The relationship is expressed mathematically as:

PV= 1/3 nm c¯2

Where; P is the pressure and V the volume occupied by any number n of

molecules of mass m having an average velocity c─.

c¯2 = 3PV/nm

Taking the square root of both sides of equation leads to:

√c¯2 = √3PV/nm
The root mean square velocity (c¯2)1/2 (usually written as µ) of the molecules in an
ideal gas. µ =(c¯2)1/2

Therefore: µ= √3PV/nm

Since the term nm/V is equal to density (d), equation becomes as:
µ= √3P/d

Where (µ) is the rate of diffusion.

Graham findings:
The rate of diffusion of a gas (µ) is inversely proportional to the square root of its
density. ( A lighter gas diffuse more rapidly through membrane than does a heavier
one).
Van der Waals Equation for Real gases:

The van der Waals equation is a modified ideal gas equation that takes into account
the factors that affect the volume and pressure of a real gas.

For 1 mole of gas: (𝑷+𝒂/𝑽𝟐)(𝑽−𝒃)=𝑹𝑻

For n moles of gas: (𝑷+𝒂𝒏𝟐/𝑽𝟐)(𝑽−𝒏𝒃)=𝒏𝑹𝑻

The term (a/V2) accounts for the internal pressure per mole resulting from the
intermolecular forces of attraction between the molecules; b accounts for
incompressibility of the molecules that is excluded volume.

The influence of non-ideality is greater when the gas is compressed (At high
pressure and low temperature).

When the volume of a gas is large(At low pressure and high temperature), the
molecules are well dispersed and far apart.
 Under these conditions, a/V2 and b become insignificant with respect to P
and V, respectively, and the van der Waals equation for the real gas reduces
to the ideal gas equation: PV = nRT
At these conditions, real gases behave in an ideal manner.

Application of van der waals equation

The van der waals equation can be rearranged as follows:

 Real gas versus Ideal gas
Real gas Ideal gas
is a gaseous compound that really exists in the It is a hypothetical gas that does not really exist
nvironment in the environment.
here are intermolecular attraction forces There are no intermolecular attraction forces
etween real gas particles between ideal gas particles

he particles have a definite volume and a mass The particles do not have a definite volume and
a mass

ollision between real gas molecules are non- Collision between ideal gas molecules are
astic elastic

netic energy of real gas particles is changed Kinetic energy of ideal gas particles is constant
ith collision

beys Van der waals equation Obeys ideal gas equation (PV=nRT)
𝑷+𝒂𝒏𝟐/𝑽𝟐)(𝑽−𝒏𝒃)=𝒏𝑹𝑻

real gas may behave as an ideal gas at low An ideal gas may behave like a real gas at high
essure and high temp. conditions. pressure and low temp. conditions.
 2- THE LIQUID STATE:
Properties of liquids:

1) Their properties lie somewhere between those of solids and gases.

2) Liquids are considerably denser than gases.

3) They have a definite volume but no definite shape.

4) Particles are further apart, and can move freely

5) They are relatively incompressible fluids. Their molecules are more tightly
packed (but not as rigid as in solids).

The transition from a gas to a liquid and from liquid to a solid

depends not only on the temperature, but also on the pressure to
which the substance is subjected.
 Liquefaction of gases
Gases are made up of molecules which are inconstant motion in all direction.
On cooling, the kinetic energy of the molecules are decreases and the
molecules come closer together and there will be intermolecular interactions.
When temp. is still lowered, molecules come closer and closer and the
intermolecular interactions become so high and the gas changes into liquid
state. Increase in pressure also brings the molecules of a gas close to one
another. So a gas can liquefied by low temp. and high pressure or a gas can
liquefied by cooling and compression.
Methods of achieving Liquefaction:
1) By subjecting the gas to intense cold by freezing.
2) Allowing the ideal gas to expand so rapidly that no heat enters the system
(adiabatic expansion).
Critical temperature:
It is the temperature above which the gas cannot be made to liquefy (the
temperature above which the liquid cannot longer exist). OR
It is the temperature below which a gas can be liquefied by more application
of pressure.
Below the critical temperature, the gas is termed as vapour and above the
critical temperature it is called a gas.
So, the liquefaction of gases is linked with the production of low temperatures.
The substances which are gaseous at ordinary temperatures can be converted
into liquid state if sufficiently cooled and simultaneously subjected to a high
pressure.
Critical pressure: The pressure required to liquefy a gas at its critical
temperature.
The critical temperature serves as a rough measure of the attractive forces
between molecules.
Substance Critical temp Critical pressure
Water 374°C, or 647 K 215 atm
Helium 5.2 K 2.26 atm

The high critical values for water result from the strong dipolar forces between
the molecules and particularly the hydrogen bonding that exists. Conversely,
only the weak London force attracts helium molecules, and, consequently, this
element must be cooled to the extremely low temperature of 5.2 K before it
can be liquefied. Above this critical temperature, helium remains a gas no
matter what the pressure.
Vapor Pressure of Liquids:

Vapor: Matter that exists in the gas state but is generally a liquid or solid at room
temperature is called vapor.
For example, Water, is a liquid at room temperature. Thus, water vapor is the
term for the gas state of water.
Translational energy of motion (kinetic energy) is not distributed evenly among
molecules; some of the molecules have more energy and hence higher velocities
than others at any moment. When a liquid is placed in an evacuated container at a
constant temperature, the molecules with the highest energies break away from
(leave) the surface of the liquid and pass into the gaseous state, and some of the
molecules subsequently return to the liquid or condense.
.
When the rate of condensation equal to the rate of vaporization at a definite
temperature, the vapor becomes saturated and a *dynamic equilibrium is
established

Equilibrium vapor pressure can be defined as the pressure of the saturated

vapor above the liquid.

Dynamic equilibrium: particles constantly move between phases, but there is

no change in the amount of particles in each phase.
Effect of Temperature on vapor Pressure of:

The vapor pressure of a liquid depends on its temperature. As the temperature

increases, the kinetic energy of the molecular motion becomes greater, and vapor
pressure increases.

Q: What happens to the vapor pressure as temperature increases?

A: The vapor pressure increases. But why?

A: Higher temperature = particles have greater kinetic energy; more kinetic

energy means particles are more able to enter the gas phase.
More particles in the gas phase = more pressure exerted because there.
all liquids: as T ↑ the VP ↑
Phase Diagrams:
Show the relationship between phase, T, and P.

• Lines separate phases; points that are on the line exhibit equilibrium between
phases.
• Critical
• Triple point: point: the point
the point on on a phase
a phase diagram at
diagram at which the
which the substance is
three states indistinguishabl
of matter: e between
gas, liquid, liquid and
and solid gaseous states.
coexist

Phase diagrams are unique for

every substance.
Clausius Clapeyron Equation:
The relationship between the vapour pressure and the absolute temperature of a
liquid is expressed by the Clausius Clapeyron Equation.

Log P2/P1 = ∆Hv(T2 _ T1) / 2.303 RT1T2

WHERE: P1 and P2 are the vapor pressure at absolute temperature T1 and T2, and
∆Hv is the molar heat of vaporization (heat absorbed by one mole of liquid when
passes into the vapor state).

Example:
Compute the vapour pressure of water at 120 0C. The vapour pressure P1 of water at
100 0C is 1 atm and ∆Hv may be taken as 9720 cal/mole for temperature range.
Solution:
P1= 1 atm P2 = ?
∆Hv = 9720 cal/mole R= 1.987cal/mole deg
T1= 100 + 273= 373K T2= 120 + 273= 393K
Log P2/P1 = ∆Hv(T2 _ T1) / 2.303 RT1T2
Boiling point (BP):

If a liquid is placed in an opened container and heated until the vapor

pressure equals the atmospheric pressure, the vapor is seen to form bubbles
that rise rapidly through the liquid and escape into the gaseous state.

The temperature at which the vapor pressure of the liquid equals the
external or atmospheric pressure is known as the boiling point.

Factors affecting boiling point:

1- Increases with the increase of molecular weight.

2- Decreases with branching of molecules (Less compact molecules with
reduced intermolecular attractions consequently decrease in the boiling
point).
Notes:
1) Non polar molecules have low B.P and low heat of vaporization because they are held
together by the London force.
2) Polar molecules like ethyl alcohol and water, which are attached through hydrogen bonds,
exhibit high boiling points and high heats of vaporization.

Examples:
• For H2O, the normal boiling point is 100.0 0C
• For CH3OH, the normal boiling point is 64.6 0C
• For C2H5OH, the normal boiling point is 78.3 0C
Latent Heat Vaporization: The amount of heat absorbed when a liquid vaporizes
at the normal boiling point. These values vary from liquid to liquid.

Aerosols:
Gases can be liquefied under high pressures in a closed chamber as long as the
chamber is maintained below the critical temperature. When the pressure is
reduced, the molecules expand and the liquid reverts to a gas. This reversible
change of state is the basic principle involved in the preparation of
pharmaceutical aerosols.
Components of aersols:
1) Drug (either dissolved or suspended in a propellant).
2) Propellant is a material that is liquid under the pressure conditions existing
inside the container and forms a gas under normal atmospheric conditions.

Filling of the container:

Two ways for filling the container:
1) Cooling the propellant and the drug to a low temperature then sealed with the
valve.
2) Sealing the drug in the container at room temperature then forcing the propellant
into the container under pressure.
In both cases, when the product is at room temp. part of propellant is in the gaseous
state and exerts the pressure necessary to extrude the drug, while the remainder is
in the liquid state and provides a solution or suspension vehicle for the drug.

Advantages of aerosols:
1) Antiseptic materials can be spread.
2) Drug can be introduced to body cavity.
 3- THE SOLID STATE;

A solid consists of an array of particles which may be atoms, ions or molecules.

These particles are held together by strong attractive forces between them. The
strength of force that exists between the particles of a solid determines the melting
point of solid.

Types of solids:
Solid can be classified according to the arrangement of particles of the solid into:
A) Crystalline solids.
B) Amorphous.
A) Crystalline solids:

Crystalline solids are in which the atoms, ions or molecules lie in an orderly array.

Properties:

1)Have definite shapes.

2)Orderly arrangement of units.

3)Incompressible.

4)They show definite melting point.

5)Passing rather sharply from solid to the liquid state.

Units of the crystal:
The units that constitute the crystal structure can be:
a) Atoms, such as Diamond and graphite.
b) Molecules, such as Carbon dioxide, hydrogen chloride and Naphthalene.
c) Ions, such as Sodium chloride.

 Ions and atoms based units are hard and brittle and have high
melting points, while molecular crystals are soft and have low
melting points.
Types of crystals:

Type Example

Cubic NaCl

Tetragonal Urea

Hexagonal Iodoform

Rhombic Iodine

Monoclinic Sucrose

Triclinic Boric acid

 Imperfection ( Lattice defects):
When a crystal has irregular external structure is considered to imperfect.

Factors responsible for crystal habit and imperfection:

1) pH of the crystalline substance.
2) Surfactant (Spans, Tweens).
3) Temperature (heating or cooling).
4) Crystal growth or seeding.

. X-Ray Diffraction:
X-rays are diffracted by crystals just as visible light is dispersed into a color
spectrum by a ruled grating.
This is due to the fact that x-rays have wavelengths of about the same magnitude as
the distance between the atoms or molecules of crystals.
Melting point:
The temperature at which the solid passes into liquid state.
The M.P of a solid depends on the strength of attractive forces that hold particles
together in the fixed position.

Freezing point:
The temperature at which a liquid passes into the solid state.

The freezing point or melting point of a pure crystalline solid is strictly defined
as the temperature at which the pure liquid and solid exist in equilibrium.
Sublimation:
Some solids on heating change to vapour without passing through the liquid state.
Examples: iodine, benzoic acid, and ammonium chloride, etc….

Latent heat of fusion:

The heat absorbed when a gram of a solid melts or the heat liberated when it
freezes.
For water at 0o C it is about 80 cal/g (1436 cal/mole).
The change in the melting or freezing point with pressure can be derived from
one form of Clapeyron equation. It is written,
∆T/∆P = T VL - Vs / ∆Hf
In which VL and Vs are the molar volumes of the liquid and solids respectively.
 Molar volume (volume in cm3 per mole) is computed by dividing the
molecular weight by the density of the compound.

∆Hf is the molar heat of fusion (that is the amount of heat absorbed when 1 mole of
the solid changes into liquid), and ∆T is the change of melting point brought about
by a pressure change of ∆P.
Polymorphism:

 Polymorphism is the ability of a solid material to exist in two or more forms or

crystalline structures of the same chemical compound and it is a solid state
phenomena.

 It is the ability of a compound to crystallize as more than one distinct

crystalline species with different internal structure. These species are
POLYMORPHS.

 Polymorphism is an exclusively solid state phenomenon.

 Polymorphs generally have different melting points, X-ray diffraction patterns,

and solubility, even though they are chemically identical.
Types of polymorphism:
Polymorphs are categorized into two types depending upon their stability
with respect to the range of temperatures and pressures :
1) Monotropic system
For monotropic system, only one polymorph is stable, which as
lower free energy content and solubility at all temperatures and
pressure below melting point and all other polymorph being
unstable.
2.)Enantiotropic system
For enantiotropic system, if one of the polymorphs is stable at
certain temperature and pressure, while the other polymorph is
stable at various temperatures and pressure.
The role of polymorphism:

1- Different polymorphism exhibit different solubility, consequently affect the rate

of dissolution of drugs.
2- One polymorph may more active than another of the same drug.

Polymorphism Example:

1) Polymorphism is exhibited in diamonds and graphite. Both diamond and

graphite are polymorphs of the same element carbon. Both the elements entirely
consist of carbon but they have different crystalline structures and physical
properties, since the structure determines the properties of the compounds.
2) Silica is also another example for polymorphism and it forms many polymorphs
such as α-quartz, β-quartz, and others.
Preparation of different polymorphic forms:
1- Precipitation. 2- Heating. 3- Melting. 4- Recrystallization.
5- Seeding of the solution to produce the desired polymorph. 6- Sublimation.
7- Pressure.
Detection of polymorphism:
1- Melting point determination. 2- Infra-red spectroscopy.
3- Differential scanning calorimetry. 4- Hot stage microscopy.
5- Dissolution rate determination.

Solvates:

When some compounds crystalize they may entrap solvent in the crystal. Crystals
that contain solvent of crystallisation are called crystal solvates, or crystal hydrates
when water is the solvent of crystallisation. Crystals that contain no water of
crystallisation are termed anhydrates.
B) Amorphous solids:

• Amorphous solids may be considered as supercooled liquids in which the

molecules are arranged in a somewhat random manner as in the liquid state.

• Amorphous solids differ from crystalline solids in that they tend to flow
when subjected to sufficient pressure over a period of time, and they do not
have definite melting points.

Amorphous substances, as well as cubic crystals, are usually isotropic, that is, they
exhibit similar properties in all directions. Crystals other than cubic are
anisotropic, showing different characteristics (electric conductance, refractive
index, crystal growth, rate of solubility) in various directions along the crystal.

Whether a drug is amorphous or crystalline has been shown to affect its therapeutic
activity. Thus, the crystalline form of the antibiotic novobiocin acid is poorly
absorbed and has no activity, whereas the amorphous form is readily absorbed and
therapeutically active.
Liquid crystalline state (LCS):
It is also known as mesophase. The material in this state is intermediate between
the liquid and solid state.

Structure of liquid crystals:

In the liquid state, molecules are mobile in three directions perpendicular to one
another.
In solid state, the molecules are immobile and rotations are not readily possible.
In liquid crystalline state, the situation is intermediate.

Types of LCS:
1) Smectic: in the smectic state, molecules are mobile in two directions and can
rotate in two directions about one axis.
2) Nematic: in the nematic state, molecules are rotate only about one axis but are
mobile in three dimensions.
3) Cholesteric crystals: considered as special case of the nematic type.
Properties of molecules from liquid crystals:
a) They are organic. b) Elongated and rectilinear in shape.
c) Rigid. d) Possess strong dipoles and easily polarizable groups.
Formation of liquid crystals:
The liquid crystalline state may result either from:
1) The heating of solids (thermotropic liquid crystals). Temperature induced
formation of the LC phases
2) The action of certain solvents on solids (lyotropic liquid crystals).
formation of LC phase upon solvation
The first recorded observation of a thermotropic liquid crystal was made by
Reinitzer in 1888 when he heated cholesteryl benzoate. At 145°C, the solid
formed a turbid liquid (the thermotropic liquid crystal), which only became clear,
to give the conventional liquid state, at 179°C.
Properties of liquid crystals:
Because of their intermediate nature, liquid crystals have some of the properties of
liquids and some of the properties of solids.

For example:

1) Liquid crystals are mobile and thus can be considered to have the flow
properties of liquids.

2) They possess the property of being birefringent,( a property associated with

crystals. In birefringence, the light passing through a material is divided into two
components with different velocities and hence different refractive indices) .

3) Some liquid crystals show consistent color changes with temperature, and this
characteristic has resulted in their being used to detect areas of elevated
temperature under the skin that may be due to a disease process.

4) Nematic liquid crystals may be sensitive to electric fields, a property used to

advantage in developing display systems.
Application of liquid crystals:
1) The smectic mesophase has application in the solubilization of water-insoluble
materials.
2) Responsible for enhanced physical stability of emulsion due to their high
viscous nature.
3) The liquid crystalline state is widespread in nature, with lipoidal forms found in
nerves, brain tissue, and blood vessels.
4) Atherosclerosis may be related to the laying down of lipid in the liquid
crystalline state on the walls of blood vessels.
5) The three components of bile (cholesterol, a bile acid salt, and water), in the
correct proportions, can form a smectic mesophase, and this may be involved in
the formation of gallstones.
6) Liquid crystals have structures that are believed to be similar to those in cell
membranes. As such, liquid crystals may function as useful biophysical models
for the structure and functionality of cell membranes.