STATES OF MATTER

AND PROPERTIES OF
MATTER

PRESENTED BY;
D.Swarupa Rani
Asst.Professor
Matter is a substance which having mass and occupies space, especially as distinct from
energy.
• Matters can be classify various ways like Physical Classification, Chemical Classification
and General Classsification.

But according to modern days Scientists there are 12 States of Matter:

1. Solid 2. Liquid 3. Gas 4. Plasma

5. Super fluid 6. Super solid 7. Bose-Einstein condensate
8. Fermionic condensate 9. String-net liquid 10. Super-critical fluid
11. Colloid 12. Degenerate matter.
Gases are compressible fluids. Their molecules are widely separated.
Liquids are relatively incompressible fluids. Their molecules are more tightly packed.
Solids are nearly incompressible and rigid. Their molecules or ions are in close contact
and do not move.
Comparison of Gases, Liquids and Solids In order for molecules to exist in aggregates in
gases, liquids and solids Intermolecular forces must exist.
Properties of Matter
 CHANGES IN STATES OF MATTER

The following are the main changes that occur in the states of matter
Freezing: Freezing is a phase transition in which a liquid turn into a solid when its
temperature is lowered below its freezing point.
Melting: Melting, or fusion, is a physical process that results in the phase transition of a
substance from a solid to a liquid. This occurs when the internal energy of the solid increases,
typically by the application of heat or pressure, which increases the substance's temperature to
the melting point.
Deposition: Deposition is a thermodynamic process, a phase transition in which gas
transforms into solid without passing through the liquid phase. The reverse of deposition is
sublimation and hence sometimes deposition is called de-sublimation. One example of
deposition is the process by which, in sub-freezing air, water vapor changes directly to ice
without first becoming a liquid. This is how snow forms in clouds, as well as how frost and
hoar frost form on the ground or other surfaces.
Sublimation: Sublimation is the transition of a substance directly from the solid to the gas
phase, without passing through the intermediate liquid phase.
Vaporization: Vaporization of an element or compound is a phase transition from the liquid
phase to vapor.
Condensation: Condensation is the change of the physical state of matter from gas phase into
liquid phase, and is the reverse of vaporisation.
 SUBLIMATION OF CRITICAL POINT
Sublimation is the change of state from a solid to a gas without passing through the liquid state.
Carbon dioxide is an example of a material that easily undergoes sublimation.
Example:
Dry ice is actually solid, frozen carbon dioxide, which happens to sublimate, or turn to gas, at a
chilly -78.5 ℃ (-109.3 degree F). The fog you see is actually a mixture of cold carbon dioxide
gas and cold, humid air, created as the dry ice melts it means sublimates.
Advantages
• For purification process, and crystallization process
• Minimum amount of product is lost
• Solvents are not used
• Most traces of any solvent in compound are effectively eliminated
• When the substance weighs less than 100mg the best method for purification is sublimation.
Disadvantages
• Recovery may not be complete – the fumes may be blown away
• Non-sublimable agent may decompose under heat
 • PHASE DIAGRAM
• Along AB line: rate at which solid sublimes to form a gas = rate at which gas condenses
to form a solid.
• Along BC line: rate at which liquid boils to form a gas = rate at which gas condenses to
form a liquid.
• Along BD line: rate at which solid melts to form a liquid =rate at which liquid freezes to
form a solid.
• Point B in this phase diagram represents the only combination of temperature and pressure
at which a pure substance can exist simultaneously as a solid, a liquid, and a gas. It is
therefore called the triple point of the substance, and it represents the only point in the
phase diagram in which all three states are in equilibrium. Point C is the critical point of
the substance, which is the highest temperature and pressure at which a gas and a liquid
can coexist at equilibrium.
 PHASE RULE

Phase rule is a rule relating the possible numbers of phases, constituents, and degrees of freedom
in a chemical system. This Rule was proposed by J. Willard Gibbs in 1876.The phase can he
defined as any homogeneous part of a system having all the physical and chemical properties.
The properties are identical throughout. A system may consist of one phase or more than one
phase.
(1) A system containing only liquid water is a single-phase or single-phase system (P =1)
(2) A system containing liquid water and steam (a gas) is a two-phase or two-phase system(P=
2).
(3) A system containing liquid water, steam and solid ice is a three-phase or three-phases. For
a system at equilibrium the phase rule relates:
P+F=C+2
Where
P = number of phases that can coexist
C = number of components making up the phases, and
F= number of independent variables or degrees of freedom.
 LATENT HEAT
In 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;
that 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.
Examples are latent heat of fusion and latent heat of vaporization involved in phase changes,
i.e. a substance condensing or vaporizing at a specified temperature and pressure.
 VAPOUR PRESSURE
The vapor pressure of a liquid is the equilibrium pressure of a vapor above its liquid (or
solid); that is, the pressure of the vapor resulting from evaporation of a liquid (or solid)
above a sample of the liquid (or solid) in a closed container.
Examples: Vapour pressure of water at 25°C is 0.03 atm and ethyl alcohol is 0.08 atm
The vapor pressure of a liquid varies with its temperature, as the following graph
shows for water.
The line on the graph shows the boiling temperature for water.As the temperature of a
liquid or solid increases its vapor pressure also increases.
Conversely,vapor pressure decreases as the temperature decreases.
Factors That Affect Vapor Pressure
1. Surface Area:
The vapor pressure is the equilibrium pressure where the rate of evaporation is equal to the rate of
condensation. Since the scaling factor is the same, the vapor pressure is independent of the
surface area.
2. Types of Molecules:
the types of molecules that make up a solid or liquid determine its vapor pressure. If the
intermolecular forces between molecules are: relatively strong, the vapor pressure will be
relatively low. relatively weak, the vapor pressure will be relatively high.
3. Temperature:
at a higher temperature, more molecules have enough energy to escape from the liquid or solid.
At a loer temperature, fewer molecules have sufficient energy to escape from the liquid or solid.
4. Intermolecular Forces: Those liquids in which the intermolecular forces are weak shows
high vapour pressure.
 Eutectic mixtures
A eutectic mixture is defined as a mixture of two or more components which usually do
not interact to form a new chemical compound but, which at certain ratios, inhibit the
crystallization process of one another resulting in a system having a lower melting point
than either of the components .
Eutectic mixtures, can be formed between Active Pharmaceutical Ingredients (APIs),
between APIs and excipient or between excipient; thereby providing a vast scope for its
applications in pharmaceutical industry.
Applications of Eutectic Mixtures in Pharmaceutical Industry
1. During pre formulation stage, compatibility studies between APIs and excipient
play a crucial role in excipient selection.
2. Testing for eutectic mixture formation can help in anticipation of probable physical
incompatibility between drug and excipient molecules.
3. Eutectic mixtures are commonly used in drug designing and delivery processes for
various routes of administration.
4. During pharmaceutical analysis, understanding of eutectic mixtures can help in the
identification of compounds having similar melting points.
 GASES
Gases are compressible fluid and has no definite shape
Properties of Gases:
1) A sample of gas assumes both the shape and volume of the container.
2) Gases are compressible.
3) The densities of gases are much smaller than those of liquids and solids and are highly
variable depending on temperature and pressure.
4) Gases form homogeneous mixtures (solutions) with one another in any proportion.
1) Boyle 's law : which provides a relationship between the pressure and the volume of a gas.
P∝ 1/V (pressure is inversely proportional to volume)
PV = C ( saying products are constant)
P1/V1= P2/V2( initial pressure, volume equal to after change pressure, volume of
product)
2) Charles Law: which provides a relationship between the volume occupied by a gas and the
absolute temperature V ∝ T
when give constant V/T =C, temperature increase volume also increase .
Initial final volume and temperature under constant pressure can be calculated. V1/T1=/V2/T2
3) Gay-Lussac's law: which provides a relationship between the pressure exerted by a gas on
the walls of its container and the absolute temperature associated with the gas.
P∝ T, P/T =C, P1/T1=P2/T2
4) Avogadro law:
which provides a relationship between the volume occupied by a gas and the amount of gaseous
substance. V∝ n
V/n=C
V1/n1= V2/n2
5)Combined gas law:
Now we can combined everything into one proportion
V ∝ T/P (volume of gas is proportional to ratio of temperature & pressure)
PV/T = C ( when given constant)
P1V1/T1= P2V2/T2
(pressure increase means temperature also increase, initial & final volumes and
temperature under constant pressure)
6) Ideal gas equation:
Also called as general gas equation, it is the equation of state of hypothetical ideal
gas.
PV=nRT
7. Dalton’s law (Partial pressure law): Daltons law describes that the total pressure
exerted by a mixture of ideal gases may be considered as sum of the partial vapour
pressures exerted by each of the ideal gases, if alone were present and occupied the
total volume.
Mathematically expressed as :
p=p1+p2+p3………..
P= total pressure of gas mixture
p1,p2,p3…. etc, = partial pressures of gases 1,2,3,………..
Applications:
Based on dalton’s law miscible liquids are classified, it is used in theory and practice of
distillation. In aerosols ,a mixture of propellants is introduced into the pressure packs, the total
pressure of the mixture is determined using dalton’s law. Pressure filling technique is used in the
manufacture of aerosols and sprays.

Kinetic Molecular Theory of Gases:

The basic assumptions of the Kinetic Molecular Theory are
1. The volume occupied by the individual particles of a gas is negligible compared to the
volume of the gas itself.
2. The particles of an ideal gas exert no attractive forces on each other or on their surroundings.
3. Gas particles are in a constant state of random motion and move in straight lines until they
collide with another body.
4. The collisions exhibited by gas particles are completely elastic; when two molecules collide,
total kinetic energy is conserved.
5. The average kinetic energy of gas molecules is directly proportional to absolute temperature
only; this implies that all molecular motion ceases if the temperature is reduced to absolute
zero.
Liquefaction of Gases: When pressure on a gas is increased, its molecules closer together, and
its temperature is reduced, which removes enough energy to make it change from the gaseous to
the liquid state.
AEROSOLS
"Aerosol is a pressurized dosage forms containing one or more therapeutic active ingredients
which upon actuation emit a fine dispersion of liquid and/or solid materials in a gaseous
medium". Aerosols are based on the principle of reversible change of state on the application
and release of pressure.

Components:
Propellants, Valves,
Container, Product concentrate, Actuator

In pharmaceutical aerosols, a drug is dissolved or suspended in a propellant, a material which

exists as a liquid under the pressure conditions prevalent inside the container but gets converted
to a gas under normal atmospheric conditions.
The container is designed in such a manner that on depressing a valve, some of the
drug propellant mixture is expelled out due to the excess pressure inside the container.
The propellant used in such a products are generally fluorinated hydrocarbons although
gases such as nitrogen and carbon dioxide and also being used.
The aerosol containers are filled either by cooling the propellant and drug to a low
temperature within the container which is then sealed with the valve.
Alternatively, the drug is sealed in the container at room temperature and the required
quantity of propellant is forced into the container under pressure.
INHALERS
An inhaler is a device holding a medicine that you take by breathing in(inhaling).
Inhalers are often used to treat chronic obstructive pulmonary disease (COPD).
There are three types of Inhalers
1. Metered-dose inhalers 2. Dry powder inhaler 3. Nebulizers
Advantages:
Fine mist drug is produced which is suitable for inhalation.
No contamination of remaining material after withdrawal of required quantity of
content. Easy to administered and medicament is directly applied to the affected area.
Then onset of action is faster compared to other dosage forms. Metred valve can
release the content in controlled and uniformly. Photosensitive medicaments can be
protected from light.
Disadvantages
cost is high and disposal of container is difficult.
RELATIVE HUMIDITY
Relative humidity is the amount of water vapor actually in the air, expressed as a
percentage of the maximum amount of water vapor the air can hold at the same
temperature When the air can't "hold" all the moisture, then it condenses as dew
Relative Humidity (percentage) = actual vapor pressure/saturated vapor pressure
x100
• At low temperature humidity is high and at high temperature humidity is low.
• Atmosphere can gain or loss water vapour.
• Relative humidity is measured by wet bulb and dry bulb hygrometer.
• Is a ratio, expressed in percent, of the amount of atmospheric moisture present
relative to the amount that would be present if the air were saturated.
• Since the latter amount is dependent on temperature, relative humidity is a function of both
moisture content and temperature.
Liquid complexes
• Complex fluids are binary mixtures that have coexistence between two phases: Solid-
liquid (suspension and solution of macromolecules such as polymers) solid-gas (granular),
liquid-gas (foams) or liquid-liquid (emulsions).
They exhibit unusual mechanical responses to applied stress or strain due to the
geometrical constraints that the phase coexistence imposes. The mechanical response
includes transitions between solid-like and fluid-like behavior as well as fluctuations.
Eg: Shaving cream is an example of a complex fluid. Without stress the foam appears to be
a solid it does not flow when adequate stress is applied, shaving cream flows easily like a
fluid.
Liquid crystals:
➤In addition to the three States of matter, some asymmetric molecules often exhibit a state
known as a liquid crystalline state or mesophase.
➤Liquid crystals possess some of the properties of liquid and some of solids.
For example liquid crystal possesses the property of mobility and rotation and thus can be
considered to have the flow properties of liquid. On the other hand, these also possess the
properties of birefringence, a property of associated with solid crystals. The birefringence,
the light passing through a material is divided into two components with different
velocities and hence different refractive index. The two main types of structure of liquid
crystal are the smectic (soap or grease like) and nematic (thread like).
➤In the smectic state, the molecules are mobile in two direction and show rotation about
one axis. In the nematic
Glassy states: All the glass is considered to be a non-conducting transparent solid, it is
actually a type of solid matter.
It can neither be considered as a typical solid nor a typical liquid.
The atoms and molecules in most solids are arranged in an orderly manner whereas in
Glassy materials these are highly disorder. Glassy materials also do not have a specific
melting point but these slowly and gradually liquefy on heating.
Although the theory behind this behaviour is not very clear, it has been shown that
material which can be converted to glassy state have a very high viscosity at their
melting point which inhibits the formation of an ordered structure
Although the most common materials which can be converted to Glassy state are the
metal oxides, even materials such as Steel can be converted to the Glassy state if it is
cooled very quickly.
This technique produces glasses since the material solidifies even before it gets
chances to develop a crystalline structure.
Solid-crystalline
The solid phase can be classified into two major categories based on the order of
molecular packing.
The most common type of state is the crystalline state in which there is both short-
range and long-range order
There is a regular structure that extends throughout the crystal
This contrasts with amorphous solids in which the regularity of structure is limited to
the immediate neighbours of any particular molecule within the solid.
Crystal structure
Crystals contain highly ordered arrays of molecules and atoms held together by non-
covalent interactions Within a specific crystal, each unit cell is the same size and
contains the same nurgber of molecules or ions arranged in the same way.
Recommended
Example: sodium chloride. Within a specific crystal, each unit cell is the same size and
contains the same number of molecules or ions arranged in the same way
Polymorphism
Polymorphism is defined as the ability of a solid material to exist in two or more
crystalline forms with different arrangements or conformation in the crystal
lattice.
The different crystalline forms are called polymorphs.
Differences in the internal structures of polymorphs result in their distinct
physical and chemical properties.
Polymorphism is the ability of solid materials to exist in two or more crystalline
forms with different arrangements of the constituents in the crystal lattice
They are packed differently in the crystal lattice or there may be differences in the
orientation of the molecules at the lattice sites.
➤These variations cause differences in the X-ray diffraction patterns of the
polymorphs and this technique is one of the main methods of detecting the
existence of polymorphs
The polymorphs have different physical and chemical properties
Various conditions in the crystallization process is the main reason responsible for
the development of different polymorphic forms.
Amorphous
Amorphous material is one kind of nonequilibrium material; its characteristic of atomic
arrangement is more like liquid and has no long-range periodicity. The glass-forming
ability of an alloy is closely related to its composition, and is quite different in various
alloys. Generally, amorphous alloy can be produced by a rapid solidification method to
freeze the liquid structure of the alloy melt, or other methods may be used that can mix
atoms to achieve a disordered state. Amorphous materials have become one of the most
actively researched fields. The deep theoretical understanding of the amorphization and
nonequilibrium state guides and promotes research and development of amorphous
materials. In this chapter, the atomic structure, formation criteria, and preparation
methods of amorphous materials are summarized, and new progress in the formation and
synthesis of bulk amorphous materials and bulk amorphous-based composites are briefly
introduced
PHYSICOCHEMICAL PROPERTIES OF DRUG MOLECULES
Introduction
For formulation development, knowledge of physical and chemical properties of drug
molecule is very important.
 Physical properties of a drug are influenced by the structural constitution of its
molecules as well as by the intermolecular forces existing within them. Hence, physical
properties help in understanding the relationship between the structure and the
mechanism of action of the drug resulting in the development of an effective
formulation.
Types of Physical Properties
1. Additive Properties: Additive property is the property of material which is due to
addition of individual property of each atom or individual functional group present in
that material. Example: Molecular weight or mass of a substance is an additive
property which is the sum of the atomic masses of its individual atoms.
2. Constitutive Properties: Constitutive property of a substance is dependent on the
arrangement of atoms and bonds in its structure. Example: Optical activity or rotation,
surface tension and viscosity.
3. Additive and Constitutive Properties: The additive and constitutive properties of a
substance are due to both, the type of atoms present in it and their intramolecular
arrangement. Example: Molar refraction, surface tension and viscosity.
4. Colligative properties:
Colligative properties are those which depend upon number of basic constituents like atom,
molecule or particles present in the solution.
Example: Freezing point depression, boiling point elevation, vapor pressure and osmotic
pressure.
 The most important physical properties of a drug molecule which helps in determining its
structural configuration include;
Dielectric constant,
Dipole moment,
Optical rotation,
Refractive index,
Surface tension and
Viscosity.
REFRACTIVE INDEX:
 A Dutch physicist called Willebrord Snell in year 1621 gave relationship between
angles when light passes from one medium to another medium.
 A beam of light when allowed to pass from one medium to another, it changes its
direction. When a beam of light is permitted to pass from a less dense medium like
air to denser medium like water the light ray turns towards the normal plane.
Similarly, when a beam of light is permitted to pass from a denser medium to a less dense
medium, the light ray turns away from the normal plane; this phenomenon in change in
direction of light is termed as refraction.

Where,
i is angle of incidence
r is angle of refraction
Refractive index (RI) is defined as ratio of velocity light in any selected medium to the velocity
of light in vacuum or air.
 Mathematically it can be represented as follows
n = velocity of light in selected material / velocity of light in vaccume or air = c/v
Refractive index is a unitless and dimensionless quantity.
 Snell’s law can also be used to describe refractive index.
This law states that refractive index is ratio of sin of angle of incidence (i) to the sin of angle of
refraction (r). n = …………………………..……………
 The major application of refractive index is to determine the purity of sample.
 Measurement of refractive index helps in determining the concentration of the solute
present in a solution.
 It helps in identifying a compound.
 It helps to determine the purity of a substance.
 It is used to determine the molar refractions of a compound which in turn provides useful
information regarding its structure.
 Refractive index can also be used for determination of molecular weights and structure of
organic compounds.
 Refractive index is used to measure refraction characteristics of solid, liquid and gases.

OPTICAL ROTATION:
An ordinary light consists of electromagnetic waves having oscillation propagating in all
directions called as unpolarized light.
When such light is passed through polarizer like Nicol prism it gets converted into light which
have oscillations propagating in only one direction. Such light is called as plane polarized
light
When any compound rotates plane polarized light passed through it through some angle, such
compound is called as optically active compound.
 This property of optically active substance is called as optical rotation and angle through
which light is rotated is called as angle of rotation.
 Optically active compounds are those who has carbon atom in centre attached to four
different groups. Such carbon atom is called as chiral carbon.
 Chiral atom is required for a molecule to show optical activity. A chiral molecule is not
superimposable on its mirror image and does not have plane of symmetry.
 For example in lactic acid central carbon atom is attached to four different groups like CH3,
H, OH and COOH.

The two isomers which are not mirror images of each other are termed as enantiomers.
 Based upon which direction plane polarized light is rotated by optically active compound
it can be classified into following two types,
When the substance turns the plane polarized light towards right side or clockwise, it is
called dextrorotatory and is denoted by (+) or (d).
clockwise, it
is called levorotatory and is denoted by (–) or (l).
 Optical rotation of a substance depends upon the wavelength of light, temperature
and
density of an optically active substance. It is an intrinsic property of an optically active
compound.

2.3.4 APPLICATIONS:
 Specific rotation helps in determining identification of compound.
 It helps in determining the purity of the substance.
 It also helps in quantitative analysis i.e., in determining the concentration of solute
in a solute.
 To study rate of reaction in chemical kinetics.
 For determination of adulterants.
DIELECTRICT CONSTANT
Capacitance is dependent upon the type of medium in between the parallel plates called as dielectric
medium and distance in between them

Ratio between the electric charges on the two parallel plates to the potential difference
between the plates is called as Capacitance (C).
C= q/v

Where, C = Capacitance
q = Electric charge
v = Potential difference
Dielectric constant (ε) is defined as ratio of capacitance of the medium Cx to the
capacitance of the vacuum Co.
ε = Cx/Co
As it is ratio dielectric constant has no unit. Dielectric constant also called as relative
permittivity of a solvent is measure of magnitude of charge separation within molecule i.e.
polarity.  Higher dielectric constant of molecule indicates high polarity means high
charge separation within the molecule. Dielectric constant affects the solubility of
substance.
Applications
 Dielectric constant is used to determine the polarity of solvents.
 Depending upon the values of dielectric constant the solvents can be arranged
accordingly which is helpful to choose the appropriate solvent with desired polarity.
 Drug solubility can be increased by choosing suitable solvent or solvent mixture
depending upon dielectric constant.
 DIPOLE MOMENT:
 Separation of opposite electric charge from each other by definite distance within a
molecule is called as dipole. Positive and negative charges are polarized within molecule due
to difference in ectronegativity of atoms.
For example in HCl, chlorine atom is more electronegative than hydrogen atom; hence
electron cloud is shifted towards chlorine molecule. Due to this hydrogen atom gains
partial positive charge and chlorine atom gains partial negative charge.
 Dipole moment can be defined as product of electric charges (e) and distance (r) between
the charges. Greek letter “μ” is used for denoting diploe moment.
μ = e × r……….……………………
Dipole is vector quantity. It has direction.
 Dipole moment is of two types, Permanent and induced.
 Permanent dipole moment is present in polar molecules which contains electronegative
molecule. While induced dipole is created within molecule by external electric field or any
other force. Unit of dipole moment is Debye which is defined as net charge present on
molecule multiplied by distance between two poles.
 Dipole moment is generally induced in asymmetric molecules. Symmetric molecules do not
show dipole moment i.e. total dipole moment is zero.
Applications:
 Dipole moment can be used for structural elucidation of molecule.
 Differentiation between cis and trans isomers can be carried out by dipole moment.
 Dipole moment also plays important role in drug - receptor binding.
 Dipole moment helps in understanding biological activity of drug molecules.
 It also helps to identify arrangement of atoms within molecule.
 Nature of bond within the atoms can be predicted by dipole moment.
DISSOCIATION CONSTANT
 Dissociation is a process by which chemical compound break down into smaller constituents.
 Most of the drugs are either weak acidic or weak basic. These drugs may undergo process of
dissociation. Dissociation may occur in solid, liquid or gaseous state.
 Dissociation of a drug molecule AxBy undergoing can be given as follows;

hense dissociation constant written as,

Where,
[A] is molar concentration of A
[B] is molar concentration of B
[AxBy] is molar concentration of AxBy.
 Dissociation constant is defined as tendency of particular substance in solution to be
dissociated into ions. It is equal to the product of respective ion concentration divided by the
concentration of non-ionic molecule. Numerically, ionization ability of a drug is given by
ionization/dissociation constant which represents the relative proton transferred or donated by
that compound.
 Degree of dissociation determines the relative amounts of ionized and unionized forms of the
drug and influences the distribution of mainly weakly acidic or weakly basic drugs.  The ratio
of ionized and unionized drugs is given by Henderson-Hasselbalch equation. pH = pKa + log
 The above Henderson - Hasselbalch equation aids in calculating the ionization
constant of compounds at a particular pH.

Dissociation constant is measured by using following methods;

Potentiometric titration
Spectrophotometric method
Calorimetry Method
Liquid Chromatography
Capillary Zone electrophoresis

Applications of Dissociation Constant:

 Dissociation constant is useful in determination of bioavailability of drug and
distribution of drug inside body in tissues.
 Dissociation of drug also affects its solubility and permeation.
 Dissociation constant is also useful in pH indicators.
 Buffer design also depends upon dissociation constant.