States of Matter and properties of matter: State of matter, changes in the state of matter, latent heats, vapour pressure, sublimation critical point, eutectic mixtures, gases, aerosols – inhalers, relative humidity, liquid complexes, liquid crystals, glassy states, solid- crystalline, amorphous & polymorphism.
Physicochemical properties of drug molecules: Refractive index, optical rotation, dielectric constant, dipole moment, dissociation constant, determinations and applications
Call Girls Kochi Just Call 9907093804 Top Class Call Girl Service Available
Unit 2 states of matter
1. • States of Matter and properties of matter: State of matter, changes
in the state of matter, latent heats, vapour pressure, sublimation
critical point, eutectic mixtures, gases, aerosols – inhalers, relative
humidity, liquid complexes, liquid crystals, glassy states, solid-
crystalline, amorphous & polymorphism.
• Physicochemical properties of drug molecules: Refractive index,
optical rotation, dielectric constant, dipole moment, dissociation
constant, determinations and applications
2. State of matter: Matter is a substance which occupies space and possesses rest mass, especially as distinct from
energy. Matters can be classify various ways like Physical Classification, Chemical Classification and General
Classification.
Physical classifications:
Solid-Ex: tablet , capsule
Liquid-Ex: oral syrup
Gas- Ex: aerosol
Chemical classifications:
Pure substance like element and compound
Mixture like homogeneous and heterogeneous
General Classification.
All substances/matter can exist in 3 states : solid, liquid and gas.
Solid - molecules are held close together in an orderly fashion with little freedom of motion.
Liquid - molecules are close together but are not held so rigidly in position and can move past one another.
Gas - molecules are separated by distances that are large compared with the size of the molecules.
3. Changes in the state of matter
• The three states of matter are inter convertable .
• The physical properties of a substance depends on the state of the substance.
• When a substance undergoes a change in state, many of its physical properties change.
• The molecules, atoms or ions in a solid are strongly held in close proximity by intermolecular, interatomic
or ionic forces respectively.
• As the temperature of a solid substance is raised the particles acquire sufficient energy to disrupt the order
arrangement and pass into the liquid state. On further increasing the temperature the molecules pass into
the gaseous state.
• As solid changes to a liquid state and then to gaseous state common is absorption of heat
• The entropy (degree of molecular randomness) of the material also increases as it goes from a solid to a
liquid and to gas.
5. Latent heat
• The word Latent means hidden
Latent heat of fusion.
The process of conversion of solid state to liquid state till it reaches to its melting point the temperature
remains constant
• When this heat results in the change of state from a solid to liquid it is known as the latent heat of fusion.
When the liquid converted into gaseous phase the temperature remains constant
For example : change in the state of a material occurs the temperature usually remains constant but heat is absorbed.
• The heat required to change ice to water at 0°C is the latent heat of fusion.
Latent heat of vaporization
• This heat which results in the change of matter without increasing the temperature is called the latent heat.
• This refers to change in enthalpy(The enthalpy H of a thermodynamic system is defined as the sum of its internal
energy and the product of its pressure and volume)
• Like wise the latent heat of vaporization is the quantity of heat absorbed when a change of state from liquid to
vapour occurs at its boiling point without changing the temperature of the material.
For example the heat required to change water to vapour at 100°C is the latent heat of vaporization.
6.
7. vapour pressure
When a liquid is kept in a closed container, molecules from its surface continuously leave and go into the free space
above it. This is known as the process of vaporization.
Some molecules however return to the surface depending on their concentration in the vapour (the process of
condensation).
Eventually a condition of equilibrium gets established when the rate of escape of molecules becomes equal to the
rate of return.
The vapour is then said to be saturated and the pressure exerted by vapour at equilibrium is known as the
vapour pressure
The vapour pressure of a liquid depends on the temperature and not on amount of liquid or vapour as long as
both liquid and vapour are present and equilibrium is maintained.
As the temperature is raised, more of the liquid goes into the vapour state and the vapour pressure increases.
As the temperature is raised further, the density of the vapour increases while that of liquid decreases.
Eventually, the densities of both the phases become equal and the two phases cannot be distinguished.
The temperature at which this happens as the critical temperature and above this the temperature; there is no
liquid-phase.
9. Sublimation
• Sublimation is defined as the process of transformation of solids directly into the vapour phase without passing
into the liquid-phase.
• The Solid substance which undergoes sublimation is called Sublime.
• The solid obtained by cooling the vapours of a solid called Sublimation.
Examples
• A number of substances including camphor, menthol, naphthalene, etc., exhibit the phenomenon of sublimation.
• Other substances such as ices can also be forced to exhibit the phenomenon of sublimation by varying the
temperature and pressure; the process being adopted during freeze drying of heat labile substances
10. Phase diagram
• A phase diagram is a convenient way of representing the phase of a substance as a function of temperature and pressure.
• Phase diagrams are produced by altering the temperature of a pure substance at constant pressure in a closed system.
• For better understanding this process is repeated at many different pressures
• The pink area in the diagram represents the solid state, the purple area represents the liquid state, and the yellow area
represents the gaseous state
• line X, shows that the phase of the substance at different temperatures at this pressure
• line crosses from solid into liquid at point A, this temperature would be the melting point of the substance.
• liquid to gas at the point C with temperature represents the boiling point of the substance at pressure X
• The line between the pink and purple areas represent the various melting points at different pressures
• The line separating the purple area from the yellow area represents the boiling point at various pressures.
• At the melting points, both solid and liquid can exist at the same time as the phase changes occurs
• At the boiling points, the substance may exist in both liquid and gas phase at the same time.
• There is one point on the diagram where all three phases may exist at one time. This point is called the triple point.
• The pressure at this point is called the triple point pressure, and the temperature at this point is called the triple point
temperature.
• There is also a line separating the pink area from the yellow area. This line represents the phase change in which a solid
changes directly to a gas without passing through the liquid phase. This phase change is known as SUBLIMATION.
• All substances undergo sublimation at the appropriate pressures. We do not see sublimation often because the pressures are
11. 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 systems (P = 2).
(3) A system containing liquid water, steam and solid ice is a three-phase
For a system at equilibrium the phase rule relates at definite temperature and pressure
P + F = C + 2 (For any system at equilibrium at definite temperature and pressure)
Where
P = number of phases that can coexist
F = number of components making up the phases, and
C= number of independent variables or degrees of freedom
12. Gas Laws
The gas laws are a group of laws that govern the behaviour of gases by providing relationships between the
following:
The volume occupied by a gas.
The pressure exerted by a gas on the walls of its container.
The absolute temperature of the gas.
The amount of gaseous substance (or) the number of moles of gas.
1) Boyle’s Law : which provides a relationship between the pressure and the volume of a gas.
2) Charles’s Law : which provides a relationship between the volume occupied by a gas and the absolute
temperature.
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.
4) Avogadro’s Law: which provides a relationship between the volume occupied by a gas and the amount of gaseous
substance.
The Combined Gas Law (or the Ideal Gas Law), which can be obtained by combining the four laws listed above.
The variations in their behaviours arise when the physical parameters associated with the gas
(such as temperature, pressure, and volume) are altered. The gas laws basically describe the behaviour of gases and
have been named after the scientists who discovered them.
13. 1) Boyle’s law equation is written as
• P ∝ 1/V
PV = k1
Where V is the volume of the gas, P is the pressure of the gas and K1 is the constant. Boyle’s Law can be used to determine the current pressure or
volume of gas and can be represented also as;
• P1V1 = P2V2
2) Charle’s law can be expressed as
• V ∝ T
Where, V = volume of gas, T = temperature of the gas in Kelvin. Another form of this equation can be written as;
• V1 / T1 = V2 / T2
3) Gay-Lussac law can be expressed as
P ∝ T
• P1 / T1 = P2 / T2
Where P is the pressure of the gas and T is the temperature of the gas in Kelvin.
4) Avogadro’s law can be expressed as
V / n = constant
Or
• V1 / n1 = V2 / n2
• Where V is the volume of an ideal gas and n in the above equation represent the number of gas molecules
14. 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 at certain ratios results the system that will be having a lowering melting point than individual components.
For example eutectic mixture of Aspirin - acetaminophen (37% and 63% respectively), and griseofulvin-succinic acid (55% and
45% respectively) dissolve rapidly than the drugs alone or their simple mixtures
• Let us consider two substances A and B
• The point A and B represent the melting point of the two
components.
• As increasing quantities of B are added to A, the freezing point
of A falls along the curve AC
• As increasing quantities of A are added to B, the freezing point
of B falls along the curve BC
• At a particular composition C, known as a eutectic point, the
mixture of the two substances has the lowest melting point.
• This composition of the two substances is known as the
eutectic mixture.
• Below the eutectic temperature the mixture of the two
substances will exist as solid while above it, the mixture will
convert into a liquid.
• The phenomenon of eutectic formation has also been used in
pharmaceutical practice to improve the dissolution behaviour
of certain drugs.
• EXAMPLE IN DEFINATION
15. Aerosols
"Aerosol is a pressurized dosage forms containing one or more therapeutic
activeingredients 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.
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
drugpropellant 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.
16. 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:
Metered -dose inhalers
Dry powder inhaler
Nebulizers
17. 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
18. 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
state, the molecules are mobile in three dimensions.
A third type known as the cholesteric crystals exist
19. 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.
20. 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 number of molecules or ions arranged
in the same way.
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.
21. 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.
22. • The conditions are generally solvent effects, presence of impurities, level of supersaturation , temperature, change
in stirring conditions, etc.
• Polymorphism may have a considerable influence on solid-state properties that may be modifies biopharmaceutical
and technological behaviour of drug.
• Drug polymorphism is related to the effects of drugs and the performance of solubility, dissolution, and
bioavailability. Thermodynamically stable polymorphs are more widely used because there are no changes during
storage, and thus have the potential to change in bioavailability.
Types of polymorphism
Enantiotropy: When the change of one polymorphic form to other at the transition temperature is reversible, the
phenomenon called Enantiotropy and the polymorphic forms are called enantiotropes. • E. g Carbamazepine •
Monotropy : Monotropy occurs when one form is stable and the other metastable. The metastable changes to the
stable form at all temperature and the change is not reversible. • E.g Chloramphenicol palmitate, Metolazone
Amorphous :
It has irregular arrangement of solid particles. The intermolecular forces are not equal. Also, the distance between
particles varies. They have undefined geometric shape. They are also called supercooled liquids.
The amorphous form of a drug often has a higher solubility than its crystalline form and the use of the amorphous
form of a drug may provide an opportunity to enhance its bioavailability in the case of poorly water-soluble drugs.
23. Some important difference between amorphous and crystalline solids.
Difference between Crystalline and Amorphous
CRYSTALLINE SOLIDS AMORPHOUS SOLIDS
Atoms are arranged in regular 3 dimension They do not have regular arrangement
Sharp melting point No particular melting point
Anisotropic :These are anisotropic in that their
physical properties are not identical in all
directions.
Isotropic : These are isotropic, that is their
physical properties are identical in all directions.
True solid Pseudo solid
Symmetrical Unsymmetrical
More rigid Less rigid
Long range order Short range order
Example: metals Ice Example: glass plastic
24. • Physicochemical properties of drug molecules: Refractive index,
optical rotation, dielectric constant, dipole moment, dissociation
constant, determinations and applications
25. Physicochemical properties of drug molecules
The study of physical and chemical properties of the drug molecule is extremely important before proceeding for
any formulation.
It often leads to better understanding of interrelationship between molecular structure and drug action.
These properties will help the formulator to decide the type of dosage form to be prepared, chances of any
incompatibilities and will also be important in deciding the stability aspects of the prepared formulation
Significance
Arrangement of an atom in the drug molecules can be obtained.
By studying the physical and chemical properties the structure of the drug molecules can be determined.
Solubility of a compound can be determined.
It gives an idea how a compound can be measures qualitatively and quantitatively.
Classifications
The physical properties can be classified as:
1. Additive property
2. Constitutive property
3. Colligative property
26. 1)Additive property: They are derived from the sum of the properties of the individual atoms or the functional
groups within the molecules.
Example: Molecular weight
2) Constitutive properties: The constitutive property depends on the structural arrangement within the molecules.
Example: Optical rotation
3) Colligative properties: The colligative property depends on the number of particles.
Example.1.Lowering of volatile point.
2. Elevation of boiling point.
3.Depression of freezing point.
The various physical properties of drug are:
Refractive index
Optical rotation
Dielectric constant
Dipole moment
Dissociation constant
27. Refractive index
• Refractive index: When a ray of light passes from one medium to another
medium it bends. This is called refraction. The refractive index of a
substance is given by
• Snell’s law.
The refractive index is constant for a substance.
n= Sin i / Sin r.
i = angle of incidence
r = angle of refraction
n = refractive index.
• The velocity of light is different in different mediums.
• This is the reason for bending of light rays, when it passes from one
medium to another.
• The medium takes the energy from light rays and so its velocity decreases
Another formula for refractive index is
Refractive index = Velocity of light in air / velocity of light in medium.
• For water, n = velocity of light in air / velocity of light in water
= 3 x 10 10 / 2.26 x 1010 = 1.33
28. REFRACTOMETRY
DEFINITION: Refractometry is the method of measuring substances refractive index (one of
their fundamental physical properties) for example, assess their composition or purity.
1. A refractometer is the instrument used to measure (RI). Although refractometers are best
known for measuring liquids, for quick evaluation of concentration of dissolved substances.
2. A refractometer measures the extent to which light is bent (i.e., refracted) when it moves from
air in to a sample and is typically used to determine the refractive index (n) of a liquid sample.
28
MEASUREMENT OF REFRACTIVE INDEX
The refractive index of different substrates measures with refractometers.
There are different types of refractometer.
They are
1.Abbe’s refractometer
2.Pulfrich refractometer
3.Immersion refractometer
4.V block refractometer
29. APPLICATIONS:
1.Assess the purity of a sample by comparing its refractive index to the
value for the pure substance.
2.Determine the concentration of a solute in a solute in a solution by
comparing the solution’s refractive index to a standard curve.
30. Optical rotation
Many substances posses the inherent property to rotate the plane of incident polarized light. This is called as
optical activist and the phenomenon is called as optical rotation.
Optical rotation is the angle at which the plane of polarization is rotated when the polarized light passes through
a layer of one liquid
Plane of polarized light:
According to the wave theory of light,
an ordinary ray of light is considered to
be vibrating in all planes at right angles to
the direction of propagation.
If this ordinary ray of light is passed through
a Nicol prism (polarising filter).
The emergent ray has its vibration in one Direction. This light having wave motion in only one plane is called as
plane polarised light. The plane along which the vibration takes place is called as plane of polarisation
31. When certain organic liquids, solutions are placed in the path of plane polarised light, the plane of
polarisation is rotated the property by virtue of which the plane of polarisation is rotated is called as
optically active substances
Substances which rotate the plane of polarised light towards right are called as dextrorotatory indicated
by “+”sign and those which rotate the plane of polarised light towards left are called laevorotatory,
indicated by “-”sign
32. Principle: It works on the principle of measuring the degree of rotation of polarized light as it passes through an optically
active substance.
Construction: The polarimeter consists of a light source (sodium vapour lamp),polarizer, as a sample cell, an analyser and
detector.
When the light is passed through the polarizer,it will get polarized. This plane polarized light is made to pass through the
sample solution filled in the sample compartment
If the sample is optically inactive ,the plane of polarized light will not change the orientation and the angle of rotation will be
0 ͦ .However if it is optically active the angle of rotation as read by the detector will be more than 0 ͦ.
33. Applications:
Specific rotation is used for determining whether or not a substance is optically active.
It can be used for measuring the purity of a substance
It can be used for determining the concentration of a substance in a solvent.
Polarimeters are used in the sugar industry to determine the quality of juice from sugarcane and refined
sucrose.
Many chemicals exhibit specific rotation as a unique prioperty that can be used to distinguish it
34. Dielectric constant
Dielectric constant Or relative permittivity (ε r) is the permittivity of the medium (ε) to the
permittivity of free space (ε˳).It is a physical property.
ε r = ε / ε˳
The parameter has no units.
The higher the dielectric constant of a solvent, the more polar it is
35. Measurement of dielectric constant:
It involves the measurement of capacitance b/w the 2 plates after
holding the test solution b/w them. After that the capacitance by
maintaining vaccum b/w the plates is measured. Then dielectric
constant is given as:
ε r = C/C˳
and C˳ = ε˳A/t
Where
C is the capacitance when the test solution is present b/w the plates,
C˳ is the capacitance when vaccum is present b/w the plates,
ε˳ is the dielectric constant of the free space, A is the surface area,
t is the thickness of the sample.
36. Applications:
Dielectric constant is used to determine the polarity of solvents.
Drug solubility can be increased by choosing suitable solvent or
solvent mixture depending upon dielectric constant
37. Dipole moment
• When non identical atoms (A & B) are joined by covalent bond, the pair of electrons will be attracted more
strongly to the atom that has higher electronegativity.
e.g: in a molecule such as HCL the bonding electron pair is not shared equally b/w hydrogen and chlorine atom.
The chlorine with greater electronegativity pulls the electron pair towards it. This gives a slightly positive
charge (+q) to the hydrogen atom and slightly negative charge (-q) to the chlorine atom.
Such a molecule with +ve charge at one end and the –ve charge at the other end is referred to as an electric
dipole or dipole and it is said to possess a dipole moment (µ ).
µ = q x r
Where,
• q is the magnitude of the separated charges and
• r is the distance b/w the two charges.
Greater the charge, larger will be dipole moment. And smaller the distance, larger will be dipole moment
38. • Measurement of dipole moment:
The dipole moment of a substance can be experimentally determined with the help of an electrical condenser. The
parallel plates of the condenser can be charged by connecting them to storage battery. When the condenser is
charged, an electric field is set up with field strength equal to the applied voltage (V) divided by distance (d) b/w
the plates.
The dipoles (polar substances) when placed b/w the charged plates, will rotate and align with the negative end
towards positive plate and positive end towards the negative plate. Thus, all the molecules will align themselves in
the electric field.
The plates are charged to a voltage V before the introduction of the polar substance. They are then disconnected
from the battery.
On introducing the polar substance b/w the plates the voltage will be to a lower value V the ratio ε = V/V˳ gives
the dielectric constant of the medium from which the dipole moment can be calculated.
39. Applications:
To determine the type of bond involved on the basis of electro negatives.
To determine the shape of molecule
To decide the type of molecule ,whether polar or nonpolar
To give an idea about the degree of polarity in case of polar molecules
40. Dissociation constant
Dissociation constant is defined as as tendency of particular substance in solution is dissociated into ions.
It is the ratio of the dissociated ions ( products) to the original acid (reactants).
It is abbreviated as Ka
The acid dissociation constant (Ka) is a quantitative measure of the strength of acid in the solution.
The dissociation constant of an acid can be determined by finding out the acid dissociates in water, when a acid is
added to water, it dissociates in it.
Some of the hydrogen atoms from the acid are added to water, leaving behind the conjugate base (reforming the
acid) continues until the products and the reactants reach to the equilibrium.
HA + H2O A¯ + H3O+
(conjugate base) (Hydronium ion)
Ka = [A¯ ] [H3O+]
[HA]
41. The equilibrium constant Ka is called the dissociation constant. It has a constant value at constant temperature.
The greater is the extent of dissociation, the greater will be the value of Ka,or the stronger is the acid, the greater
will be its Ka
Most drugs are weak electrolytes (weak acids or weak bases),their degree of ionisation depends upon the pH of
the biological fluid.
The amount of drug that exists in unionized form is a function of dissociation constant [pKa] of the fluid at the
absorption site.
pKa is the pH at which ionised and unionised forms are equal.
The Henderson-Hasselbach equation provides an estimate of the ionized and unionized drug concentration at a
particular pH.
For weak acids,
pH = pKa + log [unionised drug]/[ionized drug]
For weak bases,
pOH = pKb + log [ionized drug]/[unionized drug]
The pKa is the pH at which concentrations of ionized and unionized forms are equal. It is to express the
dissociation constant of both acidic and basic drug by pKa values. Lower the pKa of an acidic drug stronger the
acid.
Various methods can be used for determination of dissociation
Eg :NMR,UV spectroscopy,HPLC,Calorimetry etc
42. • Applications:
Dissociation constant of a drug is important as it influences many of
its biopharmaceutical properties
Dissociation constant values are important for the preparation of
appropriate buffer systems
Ionization constant [pKa] is one of the important physicochemical
properties of drugs to understand their site of absorption, distribution
to various organs and excretion.