General physical methods
• Physical properties play a vital role in characterization of
pharmaceutical chemicals and drug substances.
A wide range of physical constants, for instance :
• melting point,
• boiling point,
• specific gravity/density,
• viscosity,
• refractive index,
• solubility,
• polymorphic forms vis-a-vis particle size, in
addition to characteristic absorption features and
• optical rotation
Melting Point
• It is an important criterion to know the purity of a
substance ; however, it has a few limitations.
• The accuracy and precision of melting point is
dependent on a number of factors such as—
capillary size, sample size, initial temperature of
heating-block and the rate of rise of temperature
per unit time (minutes).
• Keeping in view the different manufacturing
processes available for a particular drug the
melting point has a definite range usually known
as the melting range.
Boiling Point
• It is also an important parameter that
establishes the purity of a substance.
• Depending on the various routes of synthesis
available for a substance a boiling point range
is usually given in different official compendia
Weight Per Milliliter
• Weight per millilitre is prevalent in the
Pharmacopoeia of India for the control of
liquid substances,
• whereas Relative Density or Specific Gravity is
mostly employed in the European
Pharmacopoeia.
Light Absorption
• The measurement of light absorption both in
the visible and ultraviolet range is employed
as an authentic means of identification of
official pharmaceutical substances.
Refractometry
• Light passes more rapidly through a vacuum than
through a substance (medium).
• It has been observed that when a ray of light
happens to pass from one medium (a) into
another medium (b) it is subjected to refraction.
• In other words, the ray travels at a lower velocity
in the relatively more optically dense medium (b)
than in medium (a) which is less optically dense.
• It is a common practice to compare the refractive
indices of liquids to that of air.
• According to Snell’s Law we have :
sin i
a b
sin r
• where, i = Angle of incidence,
• r = Angle of refraction, and
• n = Refractive index of medium (b) relative to
medium (a)
n
Refractive Index
• It is invariably used as a standard for liquids
belonging to the category of fixed oils and
synthetic chemicals.
Polarimetry
• The classical electromagnetic theory of light put
forward by Maxwell advocates that the electric and
magnetic fields associated with a beam of
monochromatic light vibrate in all directions
perpendicular to the direction of propagation of light.
• In fact, there exists an indefinite number of planes that
pass through the line of propagation, and an ordinary
light usually vibrates in all the planes.
• This is also referred to as unpolarized light.
• Under certain specific circumstances, the vibrations
may all be restricted to one direction only, in the
perpendicular plane and this is termed as planepolarized light.
• A few crystalline substances, for instance : Iceland
spar, Calcite (a form of CaCO3) or Polaroid,
possess different refractive indices for light
whose field oscillates either perpendicular or
parallel to the principal plane of the crystal.
• Thus, an ordinary light (unpolarized light) gets
converted into a plane-polarized light by simply
passing it through a lens made of the above cited
materials and traditionally called a Nicol
• prism (after William Nicol-the inventor).
• An optically active substance is one that rotates the
plane of polarized light. In other words, when a
polarized light, oscillating in a specific plane, is made to
pass through an optically active substance, it happens
to emerge oscillating in an altogether different plane.
• In general, organic molecules having a central carbon
atom to which are attached four altogether different
moieties, as C (WXYZ) thereby rendering the molecule
asymmetric, are all optically active.
• Such types of molecules usually exist in two
stereoisomeric forms as mirror images of each other
• In the above cited example [i (a)] the rotation of the
plane of polarization is to the right (clockwise),
• The lactic acid is dextrorotatory (Latin : dexter = right)
designated by ‘d’ ; if the rotation is to the left
• (counterclockwise), the lactic acid [i (b)] is levorotatory
(Latin : laevus = left) designated by ‘l’.
• In the same vein, the example [ii (b)] represents 1-2
methy1-1-butanol ; a product derived from fusel oil.
Specific Optical Rotation
• As pharmacological activity is intimately
related to molecular configuration, hence
determination of specific rotation of
pharmaceutical substances offer a vital means
of ensuring their optical purity.
Specific optical rotation
Viscosity
• Viscosity measurements are employed as a
method of identifing different grades of
liquids.
VISCOSITY
• The viscosity of liquid is a resistance to flow of
a liquid.
• All liquids appear resistance to flow change
from liquid to another, the water faster flow
than glycerin, subsequently the viscosity of
water less than glycerin at same temperature.
• Viscosity occurs as a result of contact liquid
layers with each other. The viscosity is
measuring by Ostwald viscometer.
• Relative Viscosity is the ratio of the absolute
viscosity of the fluid on the viscosity of water
at a certain temperature
The factors effect on the viscosity:
• 1. Effect of Temperature: the temperature of
the liquid fluid increases its viscosity
decreases. In gases its opposite, the viscosity
of the gases fluids increases as the
temperature of the gas increases.
• 2. Molecular weight: the molecular weight of
the liquid increases its viscosity increases.
• 3. Pressure: when increase the pressure on
liquids, the viscosity increase because increase
the attraction force between the molecules of
liquid.
• There are several formulas and equations to
calculate viscosity, the most common of which
is Viscosity = (2 x (ball density – liquid density)
x g x r2) ÷ (9 x v), where g = acceleration due to
gravity = 9.8 m/s2, r = radius of ball bearing,
and v = velocity of ball bearing through liquid.
2(bd  ld )  gr 2
Vis cos ity 
9v
Surface tension
• Surface tension is the attractive force in
liquids that pulls surface molecules into the
rest of the liquid, minimizing the surface area.
These attractive forces are due to electrostatic
forces. We typically refer to this cohesion at
the gas-liquid surface (not liquid-solid or
liquid-liquid surfaces). We often see this occur
with water, but it occurs with all other liquids
to some degree.
Surface tension calculations
F

d
Methods of surface tension
measurements
• There are several methods of surface tension
measurements:
• 1. Capillary rise method
• 2. Stallagmometer method – drop weight method
• 3. Wilhelmy plate or ring method
• 4. Maximum bulk pressure method.
• 5. Methods analyzing shape of the hanging liquid
drop or gas bubble.
• 6. Dynamic methods.
• where: d – the liquid density (g/cm3)
(actually the difference between the liquid
and the gas densities),
• g – the acceleration of gravity.
• h- capillary height , to which liquid is raised
Adsorption
• is the adhesion of atoms, ions or molecules from a
gas, liquid or dissolved solid to a surface.
• This process creates a film of the adsorbate on the
surface of the adsorbent.
• This process differs from absorption, in which
a fluid (the absorbate) is dissolved by or permeates a
liquid or solid (the absorbent),respectively.
• Adsorption is a surface phenomenon, while
absorption involves the whole volume of the
material. The term sorption encompasses both
processes, while desorption is the reverse of it.
• adsorption process is generally classified
as physisorption (characteristic of weak van
der Waals forces)
• or chemisorption (characteristic of covalent
bonding).
• It may also occur due to electrostatic
attraction.
surfactants
• Surfactants are compounds that lower the
surface tension (or interfacial tension)
between two liquids, between a gas and a
liquid, or between a liquid and a solid.
• Surfactants may act as detergents, wetting
agents, emulsifiers, foaming agents, and
dispersants
• A term surfactant comes from the word
surface active agent.
• They are amphiphilic molecules and are thus
absorbed in the air-water interface.
• At the interface, they align themselves so that
the hydrophobic part is in the air and
hydrophilic part is in water.
• This will cause the decrease in surface or
interfacial tensions.
• a
b
• If the head group has no charge, the
surfactant is called non-ionic. If the head
group has negative or positive charge, it is
called anionic or cationic, respectively.
• If it contains both positive and negative
groups, then the surfactant is called
zwitterionic.
• Anionic and nonionic surfactants are by far the
most used surfactant types in industry.
• Anionic surfactant find use especially in
cleaning product like laundry detergents and
shampoos.
• Noninonic surfactants on the other hand are
often used as wetting agents and in food
industry.
• Both cationic and zwitterionic surfactants are
more for special use as they are more
expensive to produce