States of Matter and properties of matter

By: Khalifa M Asif Y Asst. Professor Pharmaceutics Dept. AACOP Akkalkuwa

All matter exists in three states:

 A gas consists of molecules separated wide apart in
empty space.
 The molecules are free to move about throughout the
container.
 A liquid has molecules touching each other.
 However, the intermolecular space, permit the
movement of molecules throughout the liquid.
 A solid has molecules, atoms or ions arranged in a
certain order in fixed positions in the crystal lattice.
 The particles in a solid are not free to move about but
vibrate in their fixed positions.

Changes in the States of Matter

Liquefaction of Gases
 Critical phenomenon
 Critical constants
 Methods of liquefaction of gases

Critical Phenomenon
 A gas can be liquefied by lowering the temperature and increasing
the pressure.
 At lower temperature, the gas molecules lose kinetic energy. The
slow moving molecules aggregate due to attractions between them
and are converted into liquid.
 The same effect is produced by the increase of pressure. The gas
molecules come closer by compression and combine to form the
liquid.
Andrews (1869) studied the P - T conditions of liquefaction of several
gases.
He established that for every gas there is a temperature below which the
gas can be liquefied but above it the gas resists liquefaction. This
temperature is called the Critical Temperature of the gas.

Tc , Pc , and Vc are collectively called as
the Critical Constants of the gas.
Critical Temperature, Tc : The critical temperature of a gas may be
defined as that temperature above which it cannot be liquefied no matter
how great the pressure applied.
The critical pressure, Pc : The critical pressure may be defined as the
minimum pressure required to liquefy the gas at its critical temperature.
The Critical Volume, Vc : The Critical Volume may be defined as
the volume occupied by a mole of the gas at the critical temperature
and critical pressure.

At critical temperature and critical pressure, the gas
becomes identical with its liquid and is said to be in critical state.
The smooth merging of the gas with its liquid is referred to
as the Critical Phenomenon.

Methods of liquefaction of gases
If a gas is cooled below its critical temperature and then subjected to
adequate pressure, it liquefies.
The 3 important methods are :
1. Faraday’s method
2. Linde’s method
3. Claude’s method

• Faraday (1823) used freezing mixtures of ice with various salts
for external cooling of gases.
• Apparatus consist of V-shaped tube in one arm of which the gas
was prepared. In the other arm, the gas was liquefied under its
own pressure.
Faraday’s Method

 The melting of ice & dissolution of salts both are
endothermic processes. The temperature of the mixture is
lowered up to a temperature when the solution becomes
saturated.
Principle
Application
 Liquefaction of gases such as SO2, CO2, NO2 and Cl.
Limitation
 The gases having low critical points could not be liquefied by
Faraday’s method. E.g. H2, N2 and O2

Linde’s Method
 Linde (1895) used Joule Thomson effect as the basis for the
liquefaction of gases.
“When a compressed gas is allowed to expand into vacuum
or a region of low pressure, it produces intense cooling.”
 In a compressed gas the molecules are very close and the
attractions between them are appreciable. As the gas expands, the
molecules move apart. In doing so, the intermolecular attraction
must be overcome. The energy for it is taken from the gas itself
which is thereby cooled.
Principle

Apparatus

 Pure dry air is compressed to about 200 atmospheres and it is passed through
a pipe cooled by a refrigerating liquid such as ammonia.
 Here, the heat of compression is removed. The compressed air is then passed
into a spiral pipe with a jet at the lower end.
 The free expansion of air at the jet results in a considerable drop of
temperature.
 The cooled air which is now at about one atmosphere pressure passed up the
expansion chamber.
 It further cools the incoming air of the spiral tube and returns to the
compressor.
 By repeating the process of compression and expansion, a temperature low
enough to liquefy air is reached.
 The liquefied air collects at the bottom of the expansion chamber.
Working

Claude’s Method
 This method for liquefaction of gases is more efficient than that of
Linde.
 Here also the cooling is produced by free expansion of compressed
gas. But in addition, the gas is made to do work by driving an
engine.
 The energy for it comes from the gas itself which cools.
 Thus, in Claude’s method the gas is cooled not only by overcoming
the intermolecular forces but also by performance of work.
Principle

 Pure dry air is compressed to about 200 atmospheres. It is led through a tube
cooled by refrigerating liquid to remove any heat produced during the
compression.
 The tube carrying the compressed air then enters the ‘expansion chamber’.
 The tube bifurcates and a part of the air passes through the side-tube into the
cylinder of an engine. Here it expands and pushes back the piston.
 Thus the air does mechanical work whereby it cools.
 The air then enters the expansion chamber and cools the incoming compressed
air through the spiral tube.
 The air undergoes further cooling by expansion at the jet and liquefies.
 The gas escaping liquefaction goes back to the compressor and the whole
process is repeated over and over again.
Working

Latent heat
Energy absorbed or released by a substance during a change in
its physical state (phase) that occurs without changing its temperature.
 The latent heat associated with melting a solid or freezing a
liquid is called the heat of fusion;
 The latent heat associated with vaporizing a liquid or a solid or
condensing a vapour is called the heat of vaporization.
 The latent heat is normally expressed as the amount of heat (in units
of joules or calories) per mole or unit mass of the substance
undergoing a change of state.

For example,
 when a pot of water is kept boiling, the temperature remains at 100
°C (212 °F) until the last drop evaporates, because all the heat being
added to the liquid is absorbed as latent heat of vaporization and
carried away by the escaping vapour molecules.
 Similarly, while ice melts, it remains at 0 °C (32 °F), and the liquid
water that is formed with the latent heat of fusion is also at 0 °C.
 The heat of fusion for water at 0 °C is approximately 334 joules
(79.7 calories) per gram, and the heat of vaporization at 100 °C is
about 2,230 joules (533 calories) per gram.
 Because the heat of vaporization is so large, steam carries a great
deal of thermal energy that is released when it condenses, making
water an excellent working fluid for heat engines.

Vapour pressure
 When a liquid is placed in an open vessel, it evaporates. The
molecules in the liquid are moving with different kinetic energies.
 The molecules that possess above average kinetic energies can
overcome the intermolecular forces that hold them in the liquid.
 These energetic molecules escape from the liquid surface as
vapour.
 The process by which molecules of a liquid go into the gaseous
state (vapors) is called Vaporisation or Evaporation.
 The reverse process whereby gas molecules become liquid
molecules is called Condensation.

 If the liquid is placed in a closed vessel, the molecules with high
kinetic energies escape into space above the liquid.
 As the number of molecules in the gas phase increases, some of them
strike the liquid surface and get condensed.

 A stage comes when the number of molecules escaping from the liquid
is equal to the number of molecules returning to the liquid.
 In other words, the rate of evaporation exactly equals the rate of
condensation.
 Thus a dynamic equilibrium is established between the liquid and the
vapour at the given temperature.
Liquid ⇋ Vapour
 Now the concentration of the vapour in the space above the liquid will
remain unchanged with lapse of time. Hence the vapour will exert a
definite pressure at the equilibrium.
The vapour pressure of a liquid is defined as : the pressure exerted by the
vapour in equilibrium with the liquid at a fixed temperature.

Effect of Temperature on Vapour Pressure
 If the temperature of the liquid is increased, the vapour pressure will
increase because, at higher temperature more molecules in the liquid
will have larger kinetic energy and will break away from the liquid
surface.
 Also, at higher temperature, the average kinetic energy of the vapour
molecules will increase. Both vapour concentration and kinetic
energy are proportional to temperature.
Therefore, any increase of temperature
will result in the increase of vapour
pressure.

Determination of Vapour Pressure
The vapour pressure of a given liquid can be measured by
1. Static method or
2. Dynamic method.
1. The Static Method

 A sufficient amount of the liquid whose vapour pressure is to be
determined is placed in the bulb connected to a mercury manometer
and a vacuum pump.
 All the air from the bulb is removed by working the vacuum pump and
the stopcock closed.
 A part of the liquid evaporates. The system is then maintained at a
fixed temperature for enough time so that the equilibrium is
established.
The difference in the levels of mercury in the manometer is
equal to the vapour pressure of the liquid.
 This method is used for liquids having vapour pressures up to one
atmosphere.

2. The Dynamic Method

 An inert gas is passed through the given liquid at a constant
temperature (T).
 The gas saturated with the vapour of the liquid leaves the flask at the
exit tube.
 If V be the volume of the gas passed and m the loss in weight of the
liquid, the vapour pressure is given by the expression
Vapour pressure =
𝐦
𝐌𝐕
× 𝐑𝐓
Where,
M = molecular weight of the liquid and
R = gas constant.
 This method is particularly suited for liquids of very low vapour
pressure.

General Characteristics of Gases
1. Expansibility
2. Compressibility
3. Diffusibility
4. Pressure
5. Effect of Heat
Gases

Four parameters
1. Volume, V of The Gas
2. Pressure, P
3. Temperature, T
4. Number of Moles, n of Gas
Parameters Of a Gas (measurable properties)

 The volume of the container is the volume of the gas sample.
 It is usually given in liter (l or L) or milliliters (ml or mL).
 1 1itre (l) = 1000 ml and 1 ml = 10-3 l
 One ml is practically equal to one cubic centimeter (cc).
 Actually 1 liter (l) = 1000.028 cc
 The SI unit for volume is cubic meter (m3)
The Volume, V

The pressure of a gas is defined as the force exerted by the
impacts of its molecules per unit surface area in contact.
 The pressure of a gas sample can be measured with the help of a
mercury manometer.
 Similarly, the atmospheric pressure can be determined with a mercury
barometer.
The pressure, p

 The pressure of air that can support 760 mm Hg column at sea level,
is called one atmosphere (1 atm).
 The unit of pressure, millimeter of mercury, is also called torr
 Thus, 1 atm = 760 mm Hg = 760 torr
 The SI unit of pressure is the Pascal (Pa).
 The relation between Atmosphere, Torr and Pascal is :
1 atm = 760 torr = 1.013 × 105 Pa
 The unit of pressure ‘Pascal’ is not in common use.

 The temperature of a gas may be measured in Centigrade
degrees (°C) or Celsius degrees.
 The SI unit of temperature is Kelvin (K) or Absolute degree.
 The centigrade degrees can be converted to kelvins by using the
equation.
K = °C + 273
 The Kelvin temperature (or absolute temperature) is always used
in calculations of other parameters of gases.
 The degree sign (°) is not used with K.
Temperature, T

The number of moles n, of a sample of a gas in a container can be
found by dividing the mass, m, of the sample by the molar mass, M
(molecular mass).
The Moles of a Gas Sample, n
moles of gas (n) =
mass of gas sample (m)
molecular mass of gas (M)

1. Boyle’s Law
“At constant temperature, the volume of a fixed mass
of gas is inversely proportional to its pressure. If the pressure
is doubled, the volume is halved.”
Simple Gas Laws

The Boyle’s Law may be expressed mathematically as
V ∝ 1/P (T, n are constant)
or V = k × 1/P
where k is a proportionality constant.
PV= k
If P1 ,V1 are the initial pressure and volume of a given sample of gas
and P2 ,V2 the changed pressure & Volume, we can write
P1V1 = k = P2V2
P1V1 = P2V2

Graphical representation of Boyle's law.

2. Charles’s Law
“At constant pressure, the volume of a fixed mass of gas is
directly proportional to the Kelvin temperature. If the absolute
temperature is doubled, the volume is doubled.”

Charles’ Law may be expressed mathematically as
V ∝ T (P, n are constant)
or V = k T
where k is a constant.
or V/T = k
If V1 , T1 are the initial volume and temperature of a given mass
of gas at constant pressure and V2, T2 be the new values, we can
write
or

3. Avogadro’s Law
“Equal volumes of gases at the same temperature and
pressure contain equal number of moles or molecules. If the
molar amount is doubled, the volume is doubled.”

Law may be expressed mathematically as
V ∝ n (T and P constant)
or V = A n
where A is constant of proportionality.
or V/n = A
For any two gases with volumes V1, V2 and moles n1 , n2 at
constant T and P,

The Ideal Gas Equation
We have studied three simple gas laws :
Boyle’s Law V ∝ 1/P
Charles’ Law V ∝ T
Avogadro’s Law V ∝ n
These three laws can be combined into a single more general gas law :
This is called the Universal Gas Law.
“The volume of a given amount of gas is directly proportional to the
Number of moles of gas, directly proportional to the temperature, and inversely
proportional to the pressure.”
 It is also called Ideal Gas Law as it applies to all gases which exhibit ideal
behaviour i.e., obey the gas laws perfectly.

Introducing the proportionality constant R we can write
or P V = nRT
The equation (2) is called the Ideal-gas Equation or simply the general
Gas Equation. The constant R is called the Gas constant.
For one mole (n = 1) of a gas, the ideal-gas equation is reduced to
PV = RT
…………….(1)
…………….(2)

Kinetic Molecular Theory Of Gases
 Maxwell and Boltzmann (1859) developed a theory to
explain the behaviour of gases and the gas laws.
 It is based on the fundamental concept that a gas is
made of a large number of molecules in perpetual
motion.
 Hence the theory is called the kinetic molecular theory
or simply the kinetic theory of gases.

Assumptions of the Kinetic Molecular Theory
A gas consists of extremely
small discrete particles called
molecules dispersed throughout
the container.
(1)

The actual volume of the molecules is negligible
compared to the total volume of the gas.
(2)

Gas molecules are in constant random motion with high velocities.
They move in straight lines with uniform velocity and change
direction on collision with other molecules or the walls of the
container.
(3)

The distance between the molecules are very large and it is assumed
that van der Waals attractive forces between them do not exist. Thus
the gas molecules can move freely, independent of each other.
(4)
All collisions are perfectly elastic. Hence, there is no loss of the
kinetic energy of a molecule during a collision.
(5)
The pressure of a gas is caused by the hits recorded by molecules on
the walls of the container.
(6)
The average kinetic energy ( ½ mv2) of the gas molecules is directly
proportional to Kelvin temperature. This implies that the average
kinetic energy of molecules is the same at a given temperature.
(7)

Ideal Gas & Real Gases
“A gas that confirms to the assumptions of the kinetic theory of gases is
called an ideal gas.”
 It obeys the basic laws strictly under all conditions of temperature
and pressure.
“ The real gases opposed the assumptions of the kinetic theory of gases.”
e.g. hydrogen, oxygen, nitrogen etc., are opposed to the assumptions
a) The actual volume of molecules in an ideal gas is negligible, while in a real
gas it is appreciable.
b) There are no attractive forces between molecules in an ideal gas while these
exist in a real gas.
c) Molecular collisions in an ideal gas are perfectly elastic while it is not so in
a real gas.

Deviations From Ideal Behaviour
 An ideal gas is one which obeys the gas laws or the gas equation
PV = RT at all pressures and temperatures.
 However no gas is ideal.
 Almost all gases show significant deviations from the ideal
behaviour.
 Thus the gases H2 , N2 and CO2 which fail to obey the ideal-gas
equation are termed non-ideal or real gases.

Compressibility Factor
“The extent to which a real gas departs from the ideal
behaviour may be represented in terms of a new function called the
Compressibility factor ” denoted by Z
Z = PV/RT
 For an ideal gas, Z=1 and it is independent of temperature and
pressure.
 The deviations from ideal behaviour of a real gas will be
determined by the value of Z being greater or less than 1.
 For a real gas, the deviations from ideal behaviour depend on
Pressure and Temperature.

Effect of Pressure Variation on Deviations

Effect of Temperature on Deviations
Fig shows plots of Z or PV/RT against P for N2 at different temperatures.

Conclusions
1. At low pressures and fairly high temperatures, real gases
show nearly ideal behaviour and the ideal-gas equation is
obeyed.
2. At low temperatures and sufficiently high pressures, a real
gas deviates significantly from ideality and the ideal-gas
equation is no longer valid.
3. The closer the gas is to the liquefaction point, the larger will
be the deviation from the ideal behaviour.

PHARMACEUTICAL AEROSOLS

“ A system that depends on the power of a compressed or
liquefied gas to expel the contents from the container.”
“ Pressurized dosage forms containing one or more active
ingredients which upon actuation emit a fine dispersion of
liquid and/or solid materials in a gaseous medium.”
Definition

Advantages
 Removal of dose without contamination.
 Directly delivered to the affected area in a desired form.
 Minimized manual contact with drug.
 Rapid response.
 Convenient, easy.
 Controlled and uniform dosage by metered valves.
 No manual contact with patient.

Disadvantages
o Costly.
o Difficulty in disposal.
o Difficulty in formulation.
o Q.C testing is complicated.
o Cannot be subjected to heat.

Components
Aerosols consist of
1. Propellants
2. Container
3. Valve and actuator
4. Product concentrate
 API
 Additives
 Suspending agent,
 Antioxidant,
 Emulsifying agents
 Solvents
 Aqueous
 Non aqueous

Propellants
 Responsible for developing proper pressure within the container.
 Provide driving force to expel the product from the container.
Types of Propellants
1. Liquefied gases Propellant
2. Compressed gases Propellants

 Liquefied propellants are gases that exist as liquids under
pressure.
 Because the aerosol is under pressure propellant exists mainly as
a liquid, but it will also be in the head space as a gas.
 As the product is used up and the valve is opened, some of the
liquid propellant turns to gas.
Liquefied Gases Propellants
1. Hydrocarbons (HC)
2. Chlorofluorocarbon (CFC)
3. Fluorinated hydrocarbon(FHC)

Hydrocarbons
It Can be used for water based aerosols for topical use.
Advantages
 Inexpensive
 Excellent solvents
 It does not cause ozone depletion
Disadvantages
 Inflammable
 Unknown toxicity produced
Ex:
Propane - Propellant A-108
Isobutene - Propellant A-31
Butane - Propellant A-17

Advantages
• Chemical inertness
• Lack of toxicity
• Non flammability.
• Lack of explosiveness.
Propellant of choice for oral and inhalation .
Disadvantages
• High cost
• It depletes the ozone layer
Examples:
Trichloro-monofluoro-methane - Propellant 11
Dichloro-difluoro-methane - Propellant 12
Dichloro-tetrafluoro-ethane - Propellant 114
Chloro Fluoro Carbons

Examples:
Hydrofluoro Carbons & Hydro Chlorofluoro Carbons
Heptafluoro-propane - (HFA-227)
Tetrafluoro-ethane - (HFA-134a)
Difluoro-ethane - Propellant 152a
Chloro-difluoro-methane - Propellant 22
Chloro-difluoro-ethane - Propellant 142 b
These compounds break down in the atmosphere at faster rate than
CFCs. And having Lower ozone destroying effect.
Advantages
• Low inhalation toxicity
• High chemical stability
• High purity
• Not ozone depleting
Disadvantages
• Poor solvent
• High cost

Compressed Gas Propellants
 Compressed gas propellants occupy the head space above the
liquid in the can.
 When the aerosol valve is opened the gas 'pushes' the liquid out
of the can.
 The amount of gas in the headspace remains the same but it has
more space, and as a result the pressure will drop during the life
of the can.
 Spray performance is maintained however by careful choice of
the aerosol valve and actuator.
Examples: Carbon dioxide, Nitrous oxide and Nitrogen

 In Aerosol, liquefied gas propellant / propellant mixture and product
concentrate is sealed within an aerosol container, equilibrium is quickly
established between the portion of propellant that remains liquefied and
that propellant which vaporizes and occupies the upper portion of the
aerosol container.
 So, the vapor phase which develops pressure in container, against the
walls of the container. at valve assembly and the surface of the liquid
phase.
 On actuation the aerosol valve assembly is activated.
 Upon activation of the valve the pressure exerted by the propellant forces
the contents of the package to outside through the opening of the aerosol
valve.
Principle / Mechanism & working of Aerosols

 As the propellant released in to the air, it expands and evaporates
because of the drop down in pressure and form liquid droplets or dry
particles depending upon the formulation type.
 After release of some portion of the liquid phase equilibrium between
the remaining contents and the vapour state is reestablished.
 So even during expulsion of the product from the aerosol the pressure
within the container remains constant and the product may be
continuously released at same rate and with the same proportion.
 When the liquid is completely removed, the pressure cannot be
maintained, and the gas may be expelled from the container with
diminishing pressure until it is exhausted.

Container
They must be able to withstand pressures as high as 140 to 180 psig
(pounds per sq. inch gauge) at 130 ° F.
Aerosol Container
A . Metals
1. Tinplated steel
2. Aluminum
3. Stainless steel
B. Glass
1. Uncoated glass
2. Plastic coated glass

Valves
1. Continuous spray valve
2. Metering valves
Types of valves :
 Capable of delivering the content in the desired form such as
spray, foam, solid stream etc.
 It can deliver a given amount of medicament .

Continuous spray valve
Used for topical aerosols .
Valves assembly consists :

Components Made up of Uses
Mounting cup
Tin plated steel,
Al , brass
To attach valve to container.
Housing Nylon or derlin
To support Stem, Gasket,
Spring
Stem
Nylon or derlin ,
brass & stainless steel
Control the flow
Gasket
Buna-n and neoprene
rubber
To seal Valve & Can
Spring Stainless steel To hold gasket in place
Dip tube
Poly ethylene
poly propylene
To draw product

Metering Valves
 Used for dispensing of potent medication.
 Operates on the principle of a chamber whose size determines the
amount of medication dispensed.
 Approximately 50 to 150 mg ±10 % of liquid materials can be
dispensed at one time with the use of such valve.
MDI

Actuators
These are specially designed buttons which helps in delivering the
drug in desired form i.e., spray, wet stream, foam or solid stream.
Types of actuators :
 Spray actuators
 Foam actuators
 Solid steam actuators
 Special actuators

Classification of Aerosols
Aerosols may be classified as
1) Space Sprays
2) Surface coats
3) Foam

1. Space Sprays: These are finely divided sprays having particle
size up to 50 um. E.g. Insecticides, Disinfectants and Room
Deodorants etc.
2. Surface Coats: These are also sprays but disperse phase
particles are coarse with sizes up to 200 um. They produce a wet
coat when sprayed on a surface. E.g. Hair sprays, Powder sprays
and topical medicament sprays.
3. Foam: These are produced by rapid expansion of propellants
through an emulsion. Hence product comes out in the form of a
foam or froth. E.g. Shaving cream

Types of aerosol systems
1. Solution system
2. Water based system
3. Suspension or Dispersion systems
4. Foam systems
a. Aqueous stable foams
b. Non aqueous stable foams
c. Quick-breaking foams
d. Thermal foams
5. Inhalers

Solution system / 2 Phase system:
(Vapour + Liquid phase)
 Solution Aerosols are two phase systems consisting of the product
concentrate in a propellant or mixture of propellants or a mixture of
propellant and solvent.
 Solution aerosols can be difficult to formulate because many
propellant or propellant-solvent mixtures are non polar in nature and
these are poor solvents for the aerosol product concentrate.
Solvents used
 Ethyl alcohol (most commonly used solvent)
 dipropylene glycol
 propylene glycol
 ethyl acetate
 acetone

 Foot protective preparations
 Local anesthetics
 Anti-inflammatory preparations
 Spray for oral and nasal applications.
Application
Contain;
 50 to 90% propellant for topical aerosols.
 up to 99.5% propellant for oral and nasal aerosols.
Formulation

Water based system / 3 components system : (Propellant +
Water + Vapour phase)
 Large amount of water can be used to replace all or part of the non
aqueous solvents used in aerosols.
 This system is composed of a layer of water immiscible liquid
propellant, highly aqueous product concentrate and the vapour phase.
This type of system employed when the product is immiscible with the
propellant.
 Due to immiscibility of the water and propellant, it forms a three phase
aerosol.
 Ethanol used as a cosolvent to solubilize propellant in the water.
 This system emits the contents as spray or foam.

Suspension Aerosols
 Suspension Aerosols can prepare, when the product
concentrate is insoluble in the propellant or mixture of
propellant and solvent or when a co-solvent is not desirable.
 When the valve is opened or actuated, the suspension
formulation is emitted to atmosphere and the propellant rapidly
gets vaporizes and leaves a fine dispersion of the product
concentrate.
 E.g: Anti-asthmatic drugs, steroids and antibiotics are prepared
in suspension aerosols.

Foam system / Emulsion systems
 Emulsion or foam aerosols consist of Active ingredient +
Aqueous or Non aqueous vehicle + Surfactant + and propellant
(Hydrocarbon or compressed gases).
 Here the propellant which is present in the liquid acts as
internal phase.
 These aerosols dispensed as stable aqueous or non aqueous or
quick breaking foam aerosol.

Inhalers
An inhaler (puffer or pump) is a medical device used for
delivering medication into the body via the lungs and is mainly
used in the treatment of asthma and chronic obstructive
pulmonary disease.
 Aerosol inhalations are solutions, suspensions or emulsions
of drugs in a mixture of inert propellants held under
pressure in an aerosol dispenser.

Metered Dose Inhalers

Metered Dose Inhalers
MDI is the type of inhaler which on activation, releases a
fixed dose of medication in aerosol form.
 Used to minimize the number of administration errors.
 To improve the drug delivery of aerosolized particles into the
nasal passageways and respiratory tract.

Advantages of MDI:
 It delivers specified amount of dose .
 Portable and compact.
 Quick to use,
 no contamination of product.
 Dose-dose reproducibility is high.
Disadvantages of MDI :
 Low lung deposition ; high pharyngeal deposition .
 Coordination of MDI actuation and patient inhalation is
needed.

Marketed Pharmaceutical Aerosol Products
Metered Dose inhalers
Brand Name Drug Use
Flovent Diskus Fluticasone Asthma
Advair Fluticasone and Salmeterol Asthma
Aerobid Flunisolide Asthma
Qvar Beclomethasone Asthma
Proventil Albuterol Bronchospasm

Liquid Crystals
 There is a state of matter, which does not meet the necessary
requirements of any of three (solid, liquid, and gas ) categories.
For example,
A substance like cholesterol or mayonnaise is somewhere
between a liquid and a solid.
 This is not quite liquid or quite solid, but is a phase of matter whose
order is intermediate between that of a liquid and crystal.
It is often called a mesomorphic state, which is state of matter
in which the degree of molecular order is intermediate between the
perfect three dimensional, long-range positional and orientational
order found in solid crystals and the absence of long-range order
found in liquids, gases, and-amorphous solids.
 It is also called as meso intermediate.

 Physically, they are observed to flow like liquids showing some
properties of crystalline solids.
 Hence this state is considered to be the next state of matter known as
liquid crystal (LC) state.
The LC state is also known as mesophase and can be defined as
the condensed matter that exhibit intermediate thermodynamic phase
between the crystalline solid and simple liquid state.
 LCs can be considered to be crystals, which have lost some or all of
their positional order while maintaining full orientational order.
 They are free to move, but like to line up in about the same direction.
 The degree of mobility of the molecules in the LC's is less than that of
a liquid.

State Characteristics
Crystalline solids
Exhibit short as well as long-range order with regard to
both position and orientation of the molecules.
Liquids
Amorphous in general.
But may show short-range order with regard to position
and/or orientation,
Liquid crystals
Show at least orientational long-range order and may show
short-range order, whereas positional long range order
disappears.

The liquid crystals are of thermotropic and lyotropic types.
 Lyotropic liquid crystals: are induced by the presence of solvent.
 Thermotropic liquid crystals: are induced by a change in temperature and
are essentially free of solvent.
When transition between the phases is temperature dependent, as shown in
Fig., they are called thermotropic
when transitions are dependent of different components these LC's are called
lyotropic.
 Thermo tropics are mostly used in technical applications, while lytropics are
important for biological systems such as membranes.

There are three types of liquid crystals as shown in Fig.
Types of Liquid Crystals:
1. Nematic Crystal
2. Smectic liquid crystals
3. Cholesteric crystal

Nematic Crystal
 In the simple liquid crystalline state the molecules possess only
orientational but no positional order are called nematic crystal
phase. In the nematic phase the molecules can rotate about one axis
(I.e. Uniaxial) and are mobile in three directions.
 They are polarizable thread or
rod like organic molecules on
the order of 25 in lengths and
5 in height,. The order of
nematic crystal is a function of
temperature.

 A unit vector called nematic director can describe the direction of
considered alignment.
 As nematics are characterized by orientational order of the constituent
molecules, the molecular orientation and hence the material's optical
properties, can be controlled with applied electric fields.
 Nematics are the most commonly used phase in liquid crystal displays with
many such devices using the twisted nematic geometry. The schematic
presentation of twisted nematic crystal phase is shown in Fig.

Smectic liquid
 Smectic liquid crystals are characterized by one more additional degree
of positional order than nematics that the molecules can only rotate
around one axis and mobile in only two directions, (e.g. P-
ozoxyanisole.)
Cholesteric crystal
 LCs when made of asymmetric molecules that differ from their mirror
image acholesteric liquid crystal e.g. cholesterol acetate, is obtained.
 Cholesteric can be similar to nematics, but differ in the considered
orientation that it forms a helical structure with the helical axis
perpenclicular to the director.

Physical Properties:
 Physical properties of liquid crystals are anisotropic due to
orientational order.
These properties are the heat of diffusion, the magnetic
susceptibility, the dielectric permittivity or the optical
properties.
 Liquid crystals are sensitive to electrical fields, a property
that has been used in display systems.
 Liquid crystals are mobile and found to show flow properties
of liquids like rotational viscosity acting on dynamic
director deformations.

Applications
 They are best known for their application in displays.
 liquid crystals are also an essential part of all life forms.
 Lyotropic liquid crystals are essential organic substances, DNA,
lipids of cellular membranes and proteins are some examples of
well-known liquid crystals.
 The LC state is widespread in nature such as lipoidal forms
found in nerves, brain tissue and blood vessels.
 LC's may also be associated with arthrosclerosis and formation
of gallstones.
 They are believed to have structures similar to those of cell
membranes.

Glassy State
“Glass is a non-equilibrium, non-crystalline state of matter
that appears solid on a short time scale but continuously relaxes
towards the liquid state.”
 Glass, however, is actually neither a liquid-supercooled or
otherwise nor a solid.
 It is an amorphous solid; a state somewhere between those two
states of matter.
 And yet glass's liquid like properties are not enough to explain
the thicker-bottomed windows, because glass atoms move too
slowly for changes to be visible.

 When glass is made, the material (often containing silica) is quickly
cooled from its liquid state but does not solidify when its
temperature drops below its melting point.
 At this stage, the material is a supercooled liquid, an intermediate
state between liquid and glass.
 To become an amorphous solid, the material is cooled further, below
the glass-transition temperature.
 Past this point, the molecular movement of the material's atoms has
slowed to nearly a stop and the material is now a glass.
 This new structure is not as organized as a crystal, because it did not
freeze, but it is more organized than a liquid.

 For practical purposes, glass is like a disorganized solid.
 Like liquids, these disorganized solids can flow, although very slowly.
Over long periods of time, the molecules making up the glass shift
themselves to settle into a more stable, crystal like formation.
- Ediger
Glass–liquid transition
 The glass–liquid transition, or glass transition, is the gradual and
reversible transition in amorphous materials (or in amorphous regions
within semi-crystalline materials), from a hard and relatively brittle
"glassy" state into a viscous or rubbery state as the temperature is
increased.

Types of Solids
1. Crystalline solids
2. Amorphous solids
The Solids

Crystalline solids
 A crystalline solid exists as small crystals, each crystal having a
characteristic geometrical shape.
In a crystal, the atoms, molecules or ions are arranged in a
regular, repeating three-dimensional pattern called the Crystal
Lattice.
 Sugar and Sodium Chloride salt are crystalline solids.
Crystal Lattice

Amorphous solid
 An amorphous solid (amorphous = no form) has atoms, molecules
or ions arranged at random and lacks the ordered crystalline lattice.
 Examples are rubber, plastics and glass.

1. Metallic crystals: are composed of bonded metal atoms;
Example: Na, Cu, Fe, and alloys.
2. Covalent crystals: consisted of an infinite network of atoms held
together by covalent bonds, no individual molecules being present.
Example: Diamond, Graphite
3. Molecular crystals: are composed of individual molecules.
Example: Ar, Napthtalene
4. Ionic crystals: consisted of positive and negative ions;
Example: NaCl, MgO, CaCl2 and KNO3
Types of Crystalline solids

The habit of a Crystal
 The external shape is called the habit of the crystal.
 The plane surfaces of the crystal are called faces.
 The angles between the faces are referred to as the interfacial
angles.
 The habit of a crystal of a given compound depends on the rate of
development of the different faces.
 Slow growth from a slightly super-saturated solution or a very
slowly cooling solution gives large crystals.

 In the presence of certain impurities, different faces grow at different
rates and give rise to many forms.
Example,
 If Sodium Chloride is crystallised from its supersaturated
solution, it forms cubic crystals. But if urea is added as impurity,
it gives octahedral crystals.

 Different crystals of the same substance may not look alike.
But the interfacial angles are always the same.

Depending on the arrangement of faces, crystal habits can described in
deferent ways
1) Plate: each particles of similar length & width.
E.g. Naphthalene
2) Tabular: flat particles of similar length & width but possess greater
thickness and flacks
E.g. Tolbutamide

3) Equant: particles of similar length, width and height
E.g. Sodium chloride
4) Columnar: rod like particles having width and thickness exceeding
needle type particles.
E.g. Flurocortisone acetate

5) Blade: long thin flat particles.
E.g. Resorcinol
6) Acicular: needle like prisms.
E.g. Nalidixic acid

The simple basic unit or the building block of the crystal
lattice is called the Unit cell.
Crystal structure

Parameters of the Unit Cells
The unit cells may be characterized by the following parameters :
A. Relative lengths of the edges along the three axes (a, b, c).
B. The three angles between the edges (α, β, γ).

In 1850, August Bravais,(French mathematician) observed that the
crystal lattice of substances may be categorized into seven types. These
are called Bravais lattices.
𝛼 = 𝛽 = 𝛾 = 90°
𝑎 = 𝑏 = 𝑐
𝛼 = 𝛽 = 𝛾 = 90°
𝑎 = 𝑏 ≠ 𝑐

𝛼 = 𝛽 = 𝛾 ≠ 90°
𝑎 = 𝑏 = 𝑐
𝛼 = 𝛽 = 𝛾 = 90°
𝑎 ≠ 𝑏 ≠ 𝑐

𝛼 = 𝛽 = 90°
𝑎 = 𝑏 ≠ 𝑐
𝛼 ≠ 𝛽 ≠ 𝛾 ≠ 90°
𝑎 ≠ 𝑏 ≠ 𝑐
𝑎 ≠ 𝑏 ≠ 𝑐
𝛼 = 𝛽 = 90° 𝛾 ≠ 90°
𝛾 = 120°

The Seven Unit Cells

Polymorphism
“The occurrence of the same substance in more than one crystalline
forms is known as Polymorphism.”
 This phenomenon is shown by both elements and compounds.
“If an element Crystallizes as more than one distinct crystalline
species, this phenomenon is called as Allotropy”
 The individual crystalline forms of an element are referred to as
polymorphs or allotropes.
Example: Rhombic and Monoclinic Sulphur are two polymorphs or
allotropes of Sulphur.
 The polymorphic or allotropic forms of an element have distinct
physical properties and constitute separate phases.

Allotropy can be divided into three types :
1. Enantiotropy,
2. Monotropy
3. Dynamic allotropy.

Enantiotropy
 In some cases one polymorphic form (or allotrope) can change into
another at a definite temperature when the two forms have a
common vapour pressure. This temperature is known as the
transition temperature.
 One form is stable above this temperature and the other form below
it.
“ In Allotropy, when the element get changed from one
crystalline form to the other at the transition temperature is
reversible, the phenomenon is called enantiotropy.”

For example,
Rhombic sulphur (𝛼-sulphur) on heating changes to monoclinic
sulphur (ß-sulphur) at 95.6º C (transition temperature).
Also, monoclinic sulphur, on cooling, again changes to rhombic
sulphur at 95.6ºc.
That is,
95.6°C
𝛼-Sulphur ß-Sulphur

Monotropy
 It occurs when one form is stable and the other metastable.
 The metastable changes to the stable form at all temperatures and
the change is not reversible.
 Thus there is no transition temperature as the vapour pressures are
never equal.
It may be defined as irreversible change in allotropic forms of
crystals because of unequal vapour pressure and lack of transition
temperature.
Example: This type of polymorphism is exhibited by phosphorus,
White phosphorus → Red phosphorus

Dynamic allotropy
“Form of allotropy in which Some substances have several
forms which can coexist in equilibrium over a range of temperature
and are usually have different molecular formulae but the same
empirical formula, known as dynamic allotropy.”
 The amount of each is determined by the temperature.
 An example of dynamic allotropy is provided by liquid sulphur
which consists of three allotropes Sµ, Sp and Sλ.
Sµ Sp Sλ

Pharmaceutical Applications of Polymorphism
1. Enhanced Solubility
 Metastable forms have low Melting points and high solubility.
Form M.P. ºc
Aq. Solubility
(mg/ml)
Riboflavin, Form I (Stable) 291 60
Riboflavin, Form II 278 80
Riboflavin, Form III 183 1200
2. Improved dissolution
 If solubility is enhanced, the Dissolution rate also increase.
E.g. Metastable Polymorph of methylprednisolone (Form II) has 1.4
times higher rate of dissolution than Stable form (Form I)

4. Manufacture of dosage forms
 The principle of polymorphism is used in manufacturing of cocoa
butter suppositories.
Form Stability M.P. ºc
Cocoa Butter, 𝛾 Metastable 18
Cocoa Butter, 𝛼 Metastable 22
Cocoa Butter, 𝛽’ Metastable 28
Cocoa Butter, 𝛽 Stable 34.5
3. Enhanced Absorption
 As the solubility & Dissolution are enhanced, the Absorption rate
also increase.
E.g. Metastable Polymorph of methylprednisolone (Form II) has 1.7
times higher rate of Absorption than Stable form (Form I)

1. Colour change
2. Density change
3. Solubility change
4. Cooling curve method
Detection Techniques of Polymorphism

Colour change
 If a little mercury (II) iodide is placed in a melting point tube
attached to a thermometer and heated in some form of apparatus
(e.g., electrical heater), it is possible to record temperature at
which the red mercury (II) iodide changes to the yellow form.

Density change
 As rhombic sulphur changes to monoclinic sulphur, there is a
decrease in density and, therefore, an increase in volume.
 The change in volume is employed to measure the transition
temperature by using an apparatus known as Dilatometer.

Solubility change
 Two forms of the same substance have different solubilities but at
the transition point they have identical solubility.
 Thus if solubility-temperature graph is plotted for the two forms, it
is found to consist of two parts with a sharp break.
 While one part represents the solubility curve for one form, the
second part represents that for the other.
 At the meeting point of the two curves, the solubility of the two
forms is the same and it indicates the transition temperature.

Cooling curve method
 Suppose that form A is converted into form
B on heating. Now let B is allowed to cool
and a curve obtained by plotting the
temperature against the time.
 The curve will show distinct break at a
temperature corresponding to the transition
point because here heat is evolved from B.
 There is often an evolution or absorption of heat when one form passes
to the other.
 This method is suitable for determining the transition temperature
between different hydrates of a salt or between a hydrate and an
anhydrous salt or for different forms of a metal.
e.g. Na2SO4.10H2O changes to Na2SO4

Psedomorphism
“Pseudomorphs are defined as those solid forms, which arise
because of inclusion of small amount of solvent of crystallization.”
 These are also known as Solvates.
 When water is the solvent of crystallization, the crystals are
termed as Hydrates.
 Crystals that do not contain water are known as Anhydrate.
Example: Drug : Ampicillin
Pseudomorphs: Ampicillin monohydrate.
Ampicillin trihydrate.

Eutectic Mixtures
A two-component system in which the components are
completely miscible in the liquid states and are completely
immiscible in the solid state. This is because the solid phase consists
of pure component. This mixture is known as eutectic mixture.
 The temperature at which such system exists in liquid phase is
known as eutectic temperature.
 Above this temperature the components are liquid and below this
temperature they are solids.
 Physically eutectic systems are solid dispersions.
 Some examples of this type are thymol-salol, thymol-camphor,
menthol-camphor etc.

 In Fig. the melting temperature of two substances A and B are plotted against
mixture compositions.
 The curves separating the regions of A + Liquid and B + Liquid from regions
of liquid AB are termed liquidus curves.
 The horizontal line separating the fields of A + Liquid and B + Liquid from A
+ B all solid, is termed the solidus.

 Upon addition of B to A or A to B their melting points are reduced.
 The point E, where the liquidus curves and solidus intersect, is termed the
eutectic point.
 At the eutectic point in this two-component system, all three phases, that is
Liquid, crystals of A and crystals of B, all exist in equilibrium.
 The eutectic point represents a composition (eutectic mixture composition) at
which any mixture of A and B has the lowest melting point.

 If we cool solution of A and B which is richer in A than the eutectic
mixture, then the crystal of pure A will appear.
 As the solution is cooled further, more and more of A get crystallize out
and the solution becomes richer in B.
 When the eutectic point is reached, the remaining solution crystallizes
out forming a microcrystalline mixture of pure A and pure B.
Significance
 If salol-thymol combinations is to be dispensed as dry powder, it is
necessary that the ambient temperature should be below its eutectic
point of 130 °C.
 Above this temperature, it exists in liquefied form. At eutectic point
their contribution with respect to composition is 34% thymol and 66%
salol.

Physicochemical Properties
1. Refractive index
2. Optical activity
3. Dipole moment
4. Dielectric constant
5. Dissociation constant

Refractive index
 When monochromatic light passes through a less dense medium (air or
vacuum) and enters a denser medium (glass or water), the advancing waves
at interface are modified and brought closer together.
 This leads to decrease in speed and shortening of wavelength.

When light passes the denser medium, a part of wave slows
down more quickly as it passes through interface and makes it bend
towards the normal. This phenomenon is called as refraction.
 The amount of bending of light when it travel from rarer to denser
medium can be expressed as refractive index (n).
 The refractive index is a quantity which is a constant for a pure
substance under standard conditions of temperature and pressure.
 The RI of a substance is strongly influenced by temperature and
the wavelength of light used to measure it.
 This is usually written 1n2 (refractive index of material 2 with respect
to material 1.

The ratio of the speed of light in a vacuum to the speed of light
in another substance is defined as the index of refraction for the
substance.
n = index of refractive index =
speed of light in a vacuum
speed of light in a substance
or
 It is the ratio of the sine of the angle of incidence of a ray of light
on the surface separating two media to the sine of its angle of
refraction.
n = index of refraction=
sin i
sin r
Where
i = angle of incidence,
r = angle of refraction
Refractive index

Index of Refraction

Measurement of RI
 The instrument used to measure RI is called Refractrometer.
 Various refractometer used are;
1. Abbe refractometer
2. Pulfrich refractometer
3. Immersion refractometer
 Abbes refractometer is commonly used at laboratory scale because
of its advantages over other refractometer.
 It is most convenient,
 Reliable and simple instrument
 Small sample size required.
 Easy maintenance and economical.

Application of RI
 RI is an Intrinsic property of substance.
 Used in determining purity, identity.
 Used for analysis of binary mixture-glycerin water mixture.
 Determination of sugar concentration, alcohol content in fermentation.
 Unsaturation in vegetables oil determined by specific refraction.
 Molar refraction useful in study of molecular structure.

Plane Polarized Light
 According to wave theory of light, an ordinary ray light is considered to be
vibrating in all planes at right angle to the direction of propagation.
If this ordinary ray of light is passed through a polarizer (NICOL
prism), the emergent ray has its vibration only in one plane. This light having
wave motion in only one plane is known as Plane Polarized Light.
Optical activity

 Optical activity is unique character for a molecule.
A substance is said to be optically active if it rotates the plane of
the polarized light.
 The substances having ability to rotate the plane polarized light
towards clock-wise are called Dextrorotatory (+).
E.g. Dextrose
 The substances having ability to rotate the plane polarized light
towards anti-clock wise direction are called Laevorotatory (-).
E.g. Laevulose

Polarimetry : The term Polarimetry may be referred as the study of the
rotation of polarized light by transparent optically active substance.
 This measures the rotation of the polarized light as it passes through an
optically active compound.
Measurement of Optical activity
 This technique involves the
measurement of change in
the direction of vibration
of polarized light when
interact with an optically
active compound.

 The Rotatory Power of a given solution is generally expressed as
specific rotation.
It is the number of degrees of rotation of plane polarized
light produced by one gram of the substance per ml.
 The measurements is carried out at constant temp using sodium
light.
 The Specific rotation can be Calculated by the following relation:
Specific rotation
𝜶 𝝀
𝒕
=
𝜽
𝒍 × 𝒄
[α] = specific rotation,
t = temperature,
λ = wavelength,
𝜽 = optical rotation,
c = concentration in g/100ml,
l = optical path length in dm.

Applications
 Identification and Determination of Optically active compounds.
 Optical activity is the only one parameter, for distinguishing between D
& L isomeric forms.
 In Chemical industry Many chemicals exhibit a specific rotation as a
unique property which can be used to distinguish it.
 In Food, beverage and pharmaceutical industries, specific rotations can be
calculated for purity and concentration for substance like Steroids,
Diuretics, Antibiotics, Narcotics, Vitamins, Analgesics, Amino Acids,
Essential Oils, Polymers, Starches, Sugars.
 Optical rotation is used in the sugar industry for determining quality of
both juice from sugar cane and the refined sucrose.
 Polarimetry is used in remote sensing applications, such as planetary
science and weather radar.

 In a molecule such as HCl, the bonding electron pair is not shared
equally between the hydrogen atom and the chlorine atom.
 The chlorine atom with its greater electronegativity, pulls the
electron pair closer to it.
 This gives a slight positive charge (+q) to the hydrogen atom and a
slight negative charge (– q) to the chlorine atom.
Dipole moment

A molecule with a positive charge at one end and a negative
charge at the other end is referred to as an electric dipole or simply
dipole.
 The degree of polarity of a polar molecule is measured by its dipole
moment, µ.
The dipole moment of a polar molecule is given by the product
of the charge at one end and the distance between the opposite
charges.
Thus, µ = q × r

 It is represented by an arrow with a crossed tail.
 The arrow points to the negative charge and its length indicates the
magnitude of the dipole moment.
Thus a molecule of HCl may be represented as;

Unit of Dipole Moment
 The CGS unit for dipole moment is the Debye (D).
A Debye is the magnitude of the dipole moment (µ) when the
charge (q) is 1 × 10-10 esu (electrostatic units) and distance (r) is 1Å
(10-8 cm).
µ = q × r
= 1 × 10-10 × 10-8
= 1 × 10-18 esu cm
Thus 1D = 1 × 10-18 esu cm
 In SI system, the charge is stated in Coulombs (C) and distance in
meters (m). Thus dipole moment is expressed in Coulomb meters
(Cm).
 The relation of Debye to SI units is given by the expression coulomb:
1 D = 3.336 × 10-30 Cm

Determination of Dipole Moment
Electric condenser.
 The parallel plates of the condenser can be charged by connecting
them to a storage battery.
 When the condenser is charged, an electric field is set up with field
strength equal to the applied voltage (V) divided by the distance (d)
between the plates.

 Polar molecules are electric dipoles. The net charge of a dipole is
zero.
 When placed between the charged plates, it will neither move
toward the positive plate nor the negative plate.
 On the other hand, it will rotate and align with its negative end
toward the positive plate and positive end toward the negative
plate. Thus all the polar molecules align themselves in the electric
field.
 This orientation of dipoles affects the electric field between the two
plates as the field due to the dipoles is opposed to that due to the
charge on the plates.

Procedure
 Plates are charged to voltage, V prior to introduction of the polar
substance. These are then disconnected from the battery.
 On introducing the polar substance between the plates, the voltage
will change to value V’.
 Dielectric constant can be calculated by;
𝛆 =
𝑽
𝑽′
 Experimentally determined value of Dielectric constant can be used
to calculate dipole moment.

 Dipole moment provide useful information about the geometry
of molecular structure.
 Useful to study Bond moment.
 It is used to distinguish between cis and trans isomer.
 Identification of o, m and p isomers.
 Used to study ionic character of some molecules.
Application

The dielectric constant of a solvent may be defined as its capacity
to weaken the force of attraction between the electrical charges
immersed in that solvent.
 The separation of charge can be best understood from the concept of
Dielectric constant.
Dielectric constant
 The parallel plates are separated by some
medium across a distance r and connected to
voltage supply source.
 The electricity will flow across the plates from
left to right through the battery until potential
difference of the plates equals that of the
battery which is supplying the initial potential
difference.

 The capacitance, C, is equal to the amount of electric charge, q,
stored on the plates, divided by V, the potential difference, between
the plates.
 The capacitance of condenser depends on the thickness of the
condenser separating the plates.
 The Co is used as capacitance reference medium on which to
compare other mediums. The Co is the capacitance between the
plates when a vacuum fills the space between the plates.
The ratio of capacitance of test material (Cx) divided by the
capacitance of reference material is termed as dielectric constant.
C =
q
V
𝜺 =
𝑪 𝒐
𝑪 𝒙

 The polarity of the solvent depends on the dielectric constant as
more is the polar solvent greater is the dielectric constant.
Therefore dielectric constant of a substance affects the solubility
of that substance.
 The higher the value of the dielectric constant the greater is the
dissociation of the electrolyte dissolved in it because the
electrostatic forces vary inversely as the dielectric constant of
the medium.
 Water, which has a high value of dielectric constant is,
therefore, a strong dissociating solvent.
 The electrostatic forces of attraction between the ions are
considerably weakened when electrolytes are dissolved in it
and as a result, the ions begin to move freely and there is an
increase in the conductance of the solution.

 Dissociation of the electrolyte dissolved in solvents is depends
on Dielectric constant of that solvent.
 Solubility of electrolytes is correlated with Dielectric constant.
 Helps in selection of solvents for various operations.
 Used in Identification of various solvents.
Application

 When a certain amount of electrolyte (A+ B–) is dissolved in water, a
small fraction of it dissociates to form ions (A+ and B–).
 When the equilibrium has been reached between the undissociated
and the free ions, we have
AB ⇋ A+ + B–
The fraction of the amount of the electrolyte in solution
present as free ions is called the Degree of dissociation.
 If the degree of dissociation is represented by x, we can write
𝒙 =
amount dissociated (mol/L)
initial concentration (mol/L)
Dissociation constant

 The value of x can be calculated by applying the Law of Mass
Action to the ionic equilibrium for weak acid, say;
HA + H2O ⇋ A- + H3O+
 According to the Law of Mass action, the rate of forward reaction
(Rf is proportional to the concentration of reactants and the rate of
reverse reaction (Rb) is proportional to the concentration of products
Rf = K1 [HA][H20]
Rb = K2 [A-][H30 +]
At equilibrium; Rf = Rb
Solving the ratio K1/K2 we obtain
K=
𝑲 𝟏
𝑲 𝟐
=
A−
H30+
HA H20

Since [H20] is constant, equation may be written as;
K H20 =
A−
H30+
HA
= 𝑲 𝒂
where Ka=ionisation or dissociation constant of the weak acid
 pKa value refers to negative log of dissolution constant of the weak
acid.

Determination of Dissociation constant
 The dissociation constant for a weak acid or base can be obtained
by various methods such as
 Conductivity measurements,
 Visible or ultraviolet absorption spectrometry,
 Potentiometry, etc.
 Of these methods, potentiometric pH measurement is the most
widely used.

 The principle involved in this method may be understood by
referring the equation;
 when equimolar concentrations of salt [A-] and acid [HA] are
present, the dissociation constant Ka numerically is equal to the
hydronium ion concentration.
i.e. Ka =[H30+] when [A-] = [HA]
 For determination of Ka; to measure the pH of a solution containing
equimolar concentrations of the acid and a strong base salt of the
acid. At this concentration pH (which is the negative log of [H30+] is
equal to pKa.
 From pKa the Ka may be calculated.
Ka =
A−
H30+
HA
Principle of Potentiometry

 To determine degree of Dissociation of various ionic molecules.
 Helps in selection of solvents for various operations.
 Used in chemistry to study acid base reaction.
 Determination of concentration of bound molecules.
 Study of protein ligand binding.
Application

States of Matter and properties of matter

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