PHYPHAR LEC – FIRST SHIFTING EXAM METHODS OF DETERMINING THE SPECIFIC GRAVITY OF

SPECIFIC GRAVITY & DENSITY SOLIDS

A. HYDROSTATIC BALANCE METHOD
DENSITY (ρ) • Substance is immersed into the standard liquid with the
- mass per volume unit aid of a weightless thread
! ($)
ρ = & (!')
Classifications of Solids Standard Aid
ABSOLUTE density – mass is determined in vacuum Insoluble in & heavier than water Water None
APPARENT density – mass is determined in air Soluble in & heavier than water Another liquid None
Insoluble in & lighter than water Water Sinker
Difference between absolute density and apparent density Soluble in & lighter than water Another liquid sinker
• The mass of the object determined in air is influenced by Formulas
the difference in buoyant effect of air on object being Insoluble in & heavier than water
weighed and on the standard masses used for J2
comparison Sp.gr. = J2KJ(

Soluble in & heavier than water

SPECIFIC GRAVITY (Sp. gr.) J2
Sp.gr. = J2KJ x Sp. gr. of std. liq.
- weight of the substance to the weight of an equal L

volume of another substance taken as a standard Insoluble in & lighter than water
- relative density J2
Sp.gr. = J2MJ2)43
- no unit NOPQRS OP TUVRSW JNXYN & NOPQRS OP TUVRS
Gra
().+, -./-.01 203
Sp. gr. = ().+, 21 45.26 &+6.!4 +, -)217237 605.07 x Sp. gr. of std. liq. Soluble in & lighter than water
J2
Sp.gr. = J2MJ2)43 x Sp. gr. of std. liq.
or instead of the denominator, wt. of std. liq. displaced NOPQRS OP NV[. \O].W JNXYN & NOPQRS OP NV[.\O].

or loss of wt. of the subs. In the std. liq.

B. SPECIFIC GRAVITY BOTTLE OR PYCNOMETER
Standard for the determination of specific gravity: • Substance in powder form or small granules
a) Solid and liquid – water • The previously weighed substance is dropped into the
b) Gas – air or hydrogen bottle which is then filled with the standard liquid at a
Temperature at which the specific gravity of a substance is J2
Sp.gr. = temp of 25°C x Sp. gr. of std. liq.
determined ® 25°C ; for alcohol ® 15.56°C J2 M J^_` (0)a -)7.605. K J^_` (0)a -2!^64 & -)7.605.
• Powder must be agitated with a small quantity of
standard, before adding the rest to eliminate adhering
Specific gravity ranges from 0.534 to 22.48 bubbles of air, which would introduce error
• 0.543 – Lithium (Li) – lightest metal
J2
• 22.48 – Osmium (Os) – heaviest metal Sp.gr. = J2 M J^_` (0)a (2)43 K J^_` (0)a -2!^64 & (2)43 x Sp. gr. of std. liq.

In metric system, density is numerically equal to specific

gravity but not in the English system C. GRADUATED CYLINDER METHOD
• Density of water = 62.4 lb/ft3 • Direct measurement of the volume of a solid based on
• Specific gravity of water = 1 the volume it displaces when immersed in a standard
Example: liquid
Given:
J2
10 mL of water weighs 10 g Sp.gr. = b+6.+, (2)43 70-^62`47
10 mL of mercury weighs 136 g
Find the density and specific gravity of mercury D. Immersion of a solid in a transparent liquid of the same
! ($) EFG$ density
ρ= = = 13.6 g/mL
& (!') EH!' • Substance is small
().+, I$ 01 203 • Has a low specific gravity
Sp.gr. of Hg = J).+, 21 45.26 &+6.!4 +, (2)43 x Sp. gr. of water
• Insoluble in the liquid
EFG$ • Example:
Sp.gr. of Hg = x 1.0 = 13.6
EH$ Beeswax immersed in a mixture of alcohol and
water adjust by the addition of alcohol or water until
the wax floats indifferently (neither sink or rise) in the
liquid specific gravity of the wax is the same as the
liquid which is determined after the wax is removed
METHODS OF DETERMINING THE SPECIFIC GRAVITY OF
LIQUIDS
A. PYCNOMETER METHOD (Leach Pycnometer)
• Most accurate method for the determination of the
sp.gr. of liquids
• Example: Determine the specific gravity of alcohol
J^_` (0)a 26`.KJ^_` 4!^)_
Sp.gr. of alc. = J^_` (0)a (2)43KJ^_` 4!^)_
B. FLOATATION METHOD
• Archimedes’ principle
- When a solid body is placed in a liquid in which it is
capable of floating, it sinks to a depth where the
body has displaced a volume of liquid exactly equal
to its own weight
• Instruments that follow Archimedes’ principle
1. HYDROMETER – instruments calibrated to indicate
the sp.gr. of a liquid corresponding to the depth to
which the hydrometers sinks in the liquid; no unit
Type of Hydrometers
A) Constant weight with variable depth of immersion
1. Baume, Twadell, Cartier
2. Alcoholmeter – hydrometer w/ thermometer;
Tralles’, Gay-Lussac hydrometer
B) Constant depth of immersion with variable weight
1. Nicholson’s
2. Fahrenheit’s
3. Lovis’ beads (Sp.gr. beads)
o Useful in the ff. operations
- Boiling liquid is to be evaporated until
it has a given sp.gr.
- Mixing of liquids of different densities
o Balloon-shaped hollow globules of glass of
different sizes and weights
o Sp.gr. figures scratched on their sides
o Those heavier than the liquid – sink;
lighter – float
o Those remains indifferently suspended
indicates the sp.gr. of the liquid
2. MOHR WESTPHAL BALANCE
• A plummet (5mL) suspended from the beam of
the balance is immersed in the liquid to be tested
• The plummet is subjected to buoyant effect
equivalent to the liquid displaced
• The buoyant effect is measured by placing various
platinum riders/weights on the notched beam of
the balance to effect submersion of the plummet
to a constant reference point
Rider (Decimal place) Position Sp.gr. / volume
5g (0.xg) 3 0.3
.5 (0.0xg) 8 0.18
.05 (0.00xg) 4 0.004
.005 (0.000xg) 6 0.0006
C. MANOMETRIC METHOD
• Instrument: Fisher-Davidson Gravitometer
• Inverse proportionality of the density and height of the
sample and standard in the z-tube (sample) and L-tube
(standard)
• Standard: CCl4 and ethyl benzene
a40$a) +, -2!^64
=
a40$a) +, -)217237
a40$a) +, -)217237 a40$a) +, -2!^64
SPECIFIC VOLUME (sp. vol.)
- Volume of the substance to the volume of an equal
weight of another substance taken as standard
- No unit
E E E
Sp. vol. = c^.$3. = d =!
EXAMPLES:
1. A specific gravity bottle weighs 20.5 g. When filled with
water, it weighed 70.5 g . When filled with ether, it
weighed 56.75 g. 25 g of sucrose are placed in the bottle
and the latter filled with ether, it weighs 70.279g. What
is the specific gravity of
a) ether and
b) sucrose?
2. A quantity of mercuric sulfate (sp. gr. 8.12) when placed
in a pycnometer and then filled with water, the
combined weight is 69.37g. When filled with water
alone, the pycnometer weighs 40 g. Find the weight of
mercuric sulfate.
3. Calculate for the volume of 45.0g of Methanol
(sp.gr. =0.790)
4. A 1400.g of HNO3 occupies a volume of 1.0L, what is the
sp. vol.
5. A pycnometer weighs 50.0g, when filled with water, it
weighs 100.0g and when with oil, it weight 95.2g
a) What is the sp.gr. of the oil?
b) ρ
c) Sp. vol.
6. Calculate the mass of 50mL of H2SO4 (Sp. vol.= 0.56)
7. A pycnometer weighs 25.2g, when filled with water, the
combined weight is 50.8g, what is the weight of the
pycnometer when filled with syrup? (ρ = 1.31 g/mL)
MICROMERITICS – the science and technology of small particles.

METHODS OF DETERMINING PARTICLE SIZE:

1. Optical Microscopy or Microscopic Method – most accurate

The microscope eyepiece is fitted with a micrometer by which the size of the particles may
be estimated.
Unit of particle size – micrometer or micron (µm or µ)
1 µm or µ = 10-6 m, 10-4 cm, 10-3 mm
1 millimicron (mµ) = 1 nanometer (nm) = 10-9 m

2. Sieving (U.S.P. Method) – simplest

The method utilizes a series of standard sieves calibrated by the National Bureau of
Standards. This technique involves size classification followed by the determination of the
weight of each fraction.

3. Particle Volume Measurement

This method makes use of a coulter counter in determining the particle volume distribution
of material suspended in an electrolyte-containing solution.

4. Sedimentation Method – Andreasen apparatus

This method employs the settling of particles in a liquid of a relatively low density under the
influence of a gravitational or centrifugal field.

STOKE’S LAW expresses the rate of settling:

This is not applicable for particles which aggregate or clump together.

dx = V = h = d2 (ρs – ρo) g
dt t 18 η

where:
v – rate of settling or velocity of sedimentation (cm/s)
h – distance of fall in time t or ht. of liquid above the sampling tube orifice
d – diameter of particle (cm)
ρs – density of particle in dispersed phase (g/cc)
ρo – density of the dispersion medium (g/cc)
g – acceleration due to gravity (980.7 cm/s2)
η – viscosity of the dispersion medium (poise)

DERIVED PROPERTIES OF POWDERS:

1. Porosity or voids (Є)
Є = void volume x 100 = Vb – Vp x 100
bulk volume Vb

where: Vb – bulk volume

Vp – true volume

2. Packing arrangement: most powders have porosity bet. 30 – 50%

a. closest or rhombohedral – low porosity – 26%
b. open or cubic – loosest – highest porosity – 48%

1
3. Density:
a. True density (ρ = W/Vp) – density of the actual solid, exclusive of the voids and
intraparticle pores

b. Bulk or apparent density (ρ = W/Vb) – as determined from the bulk volume and the
weight of a dry powder in a graduated cylinder
Bulkiness – reciprocal of apparent density

c. Granule density – as determined by displacement of mercury, which does not penetrate

at ordinary pressure into pores smaller than about 10µm

When solid is non-porous, true density = granule density

Based on bulk density, powder may be:
a. Light – low apparent or bulk density, large bulk volume and high porosity
b. Heavy – high apparent density, small bulk volume and low porosity

4. Flow properties:
Powders may be free-flowing or cohesive depending on:
a. Particle size – as the particle size increases, flow is facilitated
b. Shape
c. Porosity
d. Density

Elongated or flat particles – loosely packed – high porosity – low density – does not flow
freely
Nearly spherical particles – closely packed – low porosity – high density – free flowing

COARSE DISPERSIONS

- those dispersions in which the size of the dispersed particle is 0.5 µm – 10 µm

1. Suspensions
2. Emulsions
3. Semisolids

1. SUSPENSIONS – coarse dispersion in which insoluble solid particles are dispersed in a liquid
medium.

A. Factors affecting sedimentation (based on Stoke’s Law)

1. Particle size and density – larger particles sediment more rapidly than smaller
particles
2. Viscosity of the medium – inversely proportional to the sedimentation rate

2. EMULSIONS – dispersed system consisting of at least two immiscible liquid phases, one of
which is dispersed as globules in other liquid phase.

A. Type of emulsion:
1. Oil in water (o/w emulsion)
2. Water in oil (w/o emulsion)

B. Methods of preparing emulsion:

1. Continental / Dry Gum
2. English / Wet Gum
3. Bottle / Forbes
2
 4. In Situ Soap

C. Methods of detecting type of emulsion:

1. Dilution test
When oil is added to an o/w emulsion or water to a w/o emulsion, separation is
apparent

2. Conductivity test
o/w emulsion – higher conductivity
w/o emulsion – no or low conductivity

3. Dye-solubility test
Water soluble dye is soluble in o/w emulsion
Oil soluble dye is soluble in w/o emulsion

D. Forms of instability:
1. Creaming and sedimentation
Creaming – is the upward movement of the dispersed droplets relative to the
continuous phase
Sedimentation – is the downward movement of the particles

2. Aggregation and coalescence

Aggregation or flocculation – the dispersed droplets come together but do not fuse
Coalescence – complete fusion of droplets leading to the ultimate separation of the
2 immiscible phases

3. Inversion – change from w/o to o/w and vice-versa brought about by:
a. Addition of electrolyte
b. Changing the phase volume ratio

3. SEMISOLIDS

Gels – a solid or semisolid system of at least 2 constituents, consisting of a condensed mass

enclosing and interpenetrated by a liquid.

A. Jelly – when the coherent matrix is liquid

Ex. Table jellies
B. Xerogel – when the liquid is removed and only the framework remains
Ex. Gelatin sheets, tragacanth ribbon and acacia tears

Changes observed in gels:

1. Syneresis – natural shrinking of a gel after standing for sometime with pressing out
some of the liquid

2. Swelling – taking up of a liquid by a gel with an increase in volume

3. Imbibition – taking up of a liquid without increase in volume

3
COLLOIDAL DISPERSIONS

- heterogeneous system in which the mean particle size of the dispersed phase is 1 nm to
0.5 µm

A. sol – colloidal dispersion of solid in liquid

B. aerosol – colloidal dispersion of solid or liquids in gases

1. Types of colloidal system based on the interaction of the particles, molecules or ions of the
dispersed phase with the molecules of the dispersion medium.

A. Lyophilic colloids (solvent-loving) – system containing colloidal particles that interact to

an appreciable extent with the dispersion medium
Ex. Gelatin, acacia

B. Lyophobic (solvent-hating) colloids – materials which have very little attraction for the
dispersion medium
Ex. Gold, silver, sulfur

C. Association or amphiphilic colloids – small molecules in dilute solution tend to associate

into aggregate (micelles) which are of colloidal dimensions
Ex. Surface active agents

2. Methods of purifying colloids:

A. Dialysis – diffusion through a membrane of parchment cellophane or collodion (removes

molecules or ions which pass through the membrane)

B. Ultrafiltration – filtration through ultrafilters prepared from colloidion impregnated with

and dried for a long period of time, allowing passage of all substances except colloidal
particles

3. Properties of colloids:

A. Optical property:
Tyndall effect – scattering of light produced when a strong beam of light is passed
through a colloidal solution

B. Kinetic property:
Brownian movement – random movement of the colloidal particles

C. Electrical property – presence of charge on the surface of particles

4
INTERFACIAL TENSION

SURFACE TENSION
INTERFACIAL TENSION
• the study of the interfacial phenomena is
concerned with the properties of the
molecules situated at or near the
boundary between two immiscible phases
called the interface or interfacial region

INTERFACE - boundary between two

immiscible phases existing together
 INTERFACE
• EXAMPLES:
• solid – solid (powder)
• solid – liquid (suspension)
• liquid – liquid (emulsion)
• solid – gas (foam)
• liquid – gas (foam)
INTERFACIAL FORCES

• Cohesive force – force of attraction

between molecules of the same phase
• Adhesive force – force of attraction
between molecules of different phases
Example: Wetting – a process in which
water forms a film over a glass or metal due
to the existence of adhesive forces
 SURFACE TENSION

SURFACE refers to either gas / solid and

gas / liquid interface

SURFACE TENSION – the force with which

the surface of one side of a line 1 cm in
length pulls or attracts the surface of the
other side of the line
 SURFACE TENSION
FACTORS AFFECTING SURFACE
TENSION:
1. Temperature – ↑ T ↓ γ
2. Adding substances:
a) electrolytes – ↑ γ of the liquid
b) non-electrolytes – ↓ γ of the liquid
SURFACE ACTIVE AGENTS

• surfactants / amphiphiles
• colloidal substances
• substances whose molecules and ions
move on their accord to the interface when
dispersed on a liquid thereby reducing
surface tension
SURFACE ACTIVE AGENTS
• amphiphatic compounds
• possess both hydrophilic (lipophobic) and
hydrophobic (lipophilic) portions
• hydrophilic portion – anionic, cationic and
non-inonic group
• hydrophobic portion – saturated and
unsaturated hydrocarbon chains,
heterocylic or aromatic systems
Natural Emulsifying agents

Acacia
Gelatin
Lecithin
Cholesterol
Agar
Methylcellulose
 Major uses of surfactants
Emulsifying agent – reduces interfacial
tension between oil and water, resulting in
minimizing surface energy through the
formation of globules
Wetting agent – aids in attaining intimate
contact between solid particles and liquids by
lowering contact angle (0º) between the
surface and the liquid; aids in the absorption if
drugs in body
Solubilizing agent
METHODS OF DETERMINING
SURFACE TENSION

1. Capillary Rise Method

2. Du Noüy Ring Method
3. Drop Weight Method
4. Others: Bubble pressure, Sessile drop,
Wilhemy plate and Pendant drop
 CAPILLARY RISE METHOD

• A capillary tube is placed in a liquid that

wets its surface, the liquid rises in the
capillary

•The height of the liquid depends on the

force of the surface tension pulling the
liquid upward, as compared to the force of
gravity pulling the liquid column downward
 CAPILLARY RISE METHOD
1
hdgr
2
• γ – surface tension (dynes/cm)
• h – height of liquid in capillary tube (cm)
• d – density of the liquid (g/cm3)
• g – acceleration of gravity (980.7 cm/s2)
• r – radius of the capillary (cm)
 DU NOÜY RING METHOD

• employs an instrument (tensiometer)

• Surface tension is based on the force
needed for the restoration of the original
position of the ring and is equal to force
necessary to pull a ring away from the
surface of the liquid
dial reading in dynes
x C. F.
exact 2 x ring circumfere nce
Du Noüy Tensiometer

Stalagmometer
 DROP WEIGHT METHOD
• Stalagmometer
• At equilibrium, upward force = downward force
2 π r γ = mg

1 m 1
where m
wt. of liquid
2 m 2 no. of drops
PHYSICAL PHARMACY

CLASSIFICATION OF SURFACTANTS:

I. Chemically:

A. ANIONS:
1. carboxylates – soaps
2. sulfonates – dialkyl sod. Sulfosuccinate such as sodium
dioctyl sulfosuccinate
3. sulfates – sodium lauryl sulfate

SOAPS:
1. alkali soaps such as K+, Na+, & NH4+ salts of lauric acid and
oleic acid o/w emulsifying agent but with disagreeable
taste therefore irritant to GIT , for external use
2. Ca, Mg & Al salts of fatty acids w/o, liniments & creams
3. Salts formed from fatty acids and an organic amine such as
triethanolamine o/w for external use

B. CATIONIC: used more as antiseptic

1. amine salts
2. quaternary amine cpds.
Ex. Tetradecyltrimethylammonium bromide
Benzalkonium chloride – inactivated in the presence
of anions; used as preservative for eye-drops

C. NON-IONIC: most stable; undissociated surfactants; most

widely used
1. sorbitan esters- sorbitan monooleate
2. glyceryl ester – glyceryl monostearate
3. Polysorbates – polyoxyethylene sorbitan monopalmitate
4. polyethylene glycol ester – polyethylene glycol 400
monostearate
5. Fatty acid alcohol – Cetomacrogol and macrogol ether –
used as emulsifying wax in o/w emulsion and solubilizing
agent for volatile oil

D. AMPHOTERIC: contains both anion and cation

Ex. Lecithin, cephalin, proteins

II. System of Hydrophile-Lipophile Classification:

- used to classify non-ionic surfactant

- HLB: 1- 10 lipophilic surfactants
- HLB: above 10 – 20 hydrophilic surfactants
 A. Lipophilic – sorbitan esters
- used as antifoaming agents, w/o emulsifying agent and wetting
agent
- commercially available as Span, Arlacel, Glyceryl monstearate

B. Hydrophilic – polyoxyethylene sorbitan esters

- used as o/w emulsifying agent, detergents and solubilizing
agent
- commerically available as Tween, Myrj, Polysorbate

Commercially available surfactants:

Span 20 – Sorbitan monolaurate

Span 40 – Sorbitan monopalmitate
Span 60 – Sorbitan monostearate
Span 65 – Sorbitan tristearate
Span 80 – Sorbitan monooleate
Span 85 – Sorbitan trioleate

Tween 20 – Polyoxyethylene Sorbitan monolaurate

Tween 40 – Polyoxyethylene Sorbitan monopalmitate
Tween 60 – Polyoxyethylene Sorbitan monostearate
Tween 65 – Polyoxyethylene Sorbitan tristearate
Tween 80 – Polyoxyethylene Sorbitan monooleate
Tween 85 – Polyoxyethylene Sorbitan trioleate

Macrogol ether
Brij 30 – Polyoxyethylene lauryl ether
Brij 72 – Polyoxyethylene stearyl ether
Brij 92 – Polyoxyethylene oleyl ether

Arlacel 83 – Sorbitan sesquioleate

Myrj 45 – Polyoxyethylene monostearate

Natural emulsifying agents:

methylcellulose, agar, gelatin, cholesterol, acacia, lecithin
RHEOLOGY: a branch of Physics which deals with the deformation and flow of
matter

Viscosity (η) (absolute) - internal friction – resistance of a fluid to flow

Unit: poise (p) or dynes-s/cm2; 1 p = 100 cp
Kinematic viscosity – absolute viscosity to density
Unit: stokes (s) or centistokes (cs)
Relative viscosity – absolute viscosity of liquid to water (no unit)

Poise (p) – unit force per unit area required to cause two parallel liquid surfaces
of unit area and unit distance apart to slide past each other with unit velocity.

Fluidity (Φ) – reciprocal of viscosity

Factors affecting viscosity:

For gas, ↑ Temp. ↑ η (independent of pressure)
For liquid, ↑ Temp. ↓ η ↑ Φ
↓ MW, ↓ η
+ electrolytes, ↓ η
+ org. subs., ↑ η

Newton’s Law of Flow:

The higher the viscosity of a liquid, the greater the shearing stress is
required to produce certain of rate of shear.

Classification of Liquids according to the type of Flow:

A. Newtonian – shear stress is directly proportional to the rate of shear

B. Non-newtonian:
1. Plastc flow:
a) associated with flocculated particles (stick together)
b) presence of yield value (stress at which flow begins)
c) at stresses above yield value, materials turn into free-flowing
Ex. Ointments, pastes, creams, cataplasms, cerates, butter, and margarine

2. Pseudoplastic flow
a) shear thinning behavior
b) viscosity decreases with increase rate of shear
c) exhibited by polymers in solution
d) rate of shear increases faster than shear stress

Ex. Natural and synthetic gums, liquid dispersion of tragacanth, sodium

alginate, methylcellulose
 3. Dilatant flow
a) shear thickening
b) associated with particles which do not tend to aggregate or stick together
c) viscosity increases with increase rate of shear
d) viscosity increases with agitation

Ex. Paint, suspension ( ≥ 50% conc.)

Thixotropy – reversible sol-gel transformation which is used in some

pharmaceutical formulations
Ex. Aqueous dispersion of sodium bentonite, Colloidal SiO2, Magnesium
bentonite

INSTRUMENTS FOR DETERMINING VISCOSITY:

A. Single- point viscometer
1. Capillary viscometer – Ostwald v. and Saybolt v.
2. Falling sphere viscometer – Hoppler v.

B. Multi-point viscometer
1. Cup and Bob V.
a. Searle type – bob is rotating
Stormer v., Haake-Rotovisko, Brookfield Synchro-Lectric viscometer
b. Couette type – cup is rotating
MacMichael v., Coaxial-cylinder v.
2. Cone and plate viscometer – Ferranti-Shirley v.

C. Others:
Penetrometers for ointments
Measurement for viscoelasticity
Optical activity
- property of substances possessing the
power of rotating the plane of polarized
light

Condition for a molecule to show

optical activity:
- Dissymmetric (contains a chiral carbon)
- Molecule should not superimposed with
its mirror image
Enantiomorphs / enantiomers /
optical antipodes

Enantios – opposite
Morphs – forms

- molecule whose mirror images are

non-superimposable
-Rotate the plane of polarized light to the
same degree but in opposite directions
All amino acids are optically active
except glycine.
R – CH – COOH
NH2
Specific rotation (solution) /
Optical rotation (pure substance)

- angular rotation in degrees thru which

the plane of polarization of light is
rotated when the polarized light passes
thru a one decimeter layer of the liquid at
a specified temperature
Polarimeter
Optical Rotatory Dispersion:
- measurement of the angle of optical
rotation at various wavelength
- serves as a basis for determining
purity and identity of substances
•optical activity is a function of
chemical constitution as well as
concentration
 MOLAR
REFRACTION
INTRODUCTION:
• light travels in straight line
• transmitting medium have same
density
• water has higher optical density
than air
• speed of light is reduced as it
enters water
Light ray enters the denser
medium:
• normal to the boundary, no
refraction occurs
• at oblique angle, refraction occurs
and ray is bent toward the normal
REFRACTION
• bending of light rays
• pass obliquely
• from one medium to another
• different optical densities
REFRACTIVE INDEX (n)
- ratio of the velocity of light in air to its
velocity in a material under like
conditions

n v 1 sin i
r
v 2
sin r
REFRACTIVE INDEX:
• characteristic of a substance with
temperature and wavelength
• as T , n due to a in optical
compactness
• shorter waves are refracted more
than longer waves
USES OF REFRACTIVE INDEX:
• To identify a substance
• To measure purity of a substance
• to determine the concentration of
the substance in another
THEORY OF REFRACTION:
- When a light ray passes
obliquely upon the interface of two
substances of different densities,
an abrupt change in the direction of
the beam in the second medium is
observed.
THEORY OF REFRACTION:
• If angle of incidence is increased
where the angle of refraction =
90°, light passes along the
surface of the boundary of the two
media
• the angle of incidence known as
critical angle
THEORY OF REFRACTION:
• If angle of incidence > critical
angle, total reflection will occur.
REFRACTOMETER or
INTERFEROMETER
- instrument to measure refractive
index
- Critical angle refractometer (Abbe) –
most widely used
- white light or monochromatic
radiation ( Sodium doublet line at
589.6 nm or mu)
REFRACTOMETER
MOLAR REFRACTION (Rm)
- product of specific refraction (rd)
and molecular weight (MW)
- sum of atomic, group and bond
refractions in a molecule
Significance:
• differentiate keto (-C=O) and enol
(=C-OH) tautomers
REACTIONS KINETICS – the study of the rates at which reactions take place

RATE OF REACTION – measures the moles of reactants disappearing or mole

of product appearing per unit time

FACTORS AFFECTING / INFLUENCING THE RATE OF CHEMICAL

REACTION:
1) concentration
2) temperature

I. Concentration:
Reaction order – refers to the way in which concentration of the reactant
influences the rate of chemical reaction

1) Zero-order reaction is used for long-term stability studies

2) First-order reaction is used for accelerated stability studies.
3) Second-order reaction which involves a single reactant may also be
encountered
a. The solvent concentration (water is held constant by having a large
excess. The reaction becomes a pseudo-first order or an apparent
first order reaction. This depends on the concentration of the
drug.
EX. SOLUTIONS (soluble drug)

b. The water is held constant and there is a large excess of insoluble

drug. The reaction becomes pseudo-zero order reaction. The
reaction depends on the solubility of the drug and not the
concentration.
Ex. SUSPENSIONS (insoluble drug)

4) Shelf-life (t90) – the time when 10% of the drug has been lost (90%
remaining)
5) Half-life (t1/2) – the time when 50% of the drug has been lost (50%
remaining)

II. Temperature: Energy of Activation

Reaction rates are proportional to the number of collisions per unit time.
Since the number of collisions increases as the temperature increases, the
reaction rate is expected to increase with increased temperature.

Energy of activation (Ea) – the additional energy possess by reactants above

its average energy for a reaction to take place. The lower the Ea, the less stable
is the drug.
 REACTION ORDER CLASSIFICATION
ZERO-ORDER FRIST-ORDER SECOND-ORDER
1.CHARAC- Rate pf rxn. Is Rate of rxn. is Rate of rxn. Is
TERISTICS independent of the proportional to the first proportional to the
concentration of power of the conc. of the product of the conc.
the reactants reactants of 2 atoms or
molecules (may be
the same kind or of
different kinds)
2. SAMPLE ______________ Decay of radioactive Combination of
REACTIONS atoms, decomposition hydrogen and
rxn. Hydrolysis rxn. oxygen,
(pseudo-first order rxn.) decomposition of HI,
1 Br2 → 2Br hydrolysis of ester in
1 N2O5 → N2O4 + ½ O2 alkaline solution
(saponification)
2HCl H2↑ + Cl2↑
CH3COOH+C2H5OH
CH3COOC2H5+
H2O
3. KINETIC Conc. vs. time Conc. vs. time-
PROFILE - linear curvilinear
Log conc. vs. time –
linear
4. t1/2 0.5 [D]o / Ko 0.693/K1

5. t90 0.1[D]o / Ko 0.105/K1

 Osmosis
• spontaneous process
• diffusion of water across a semi-
permeable membrane
• semi-permeable membrane
allows passage of solvent but not
solute
 Osmosis
• movement of solvent from lower
solute concentration to higher
solute concentration

• movement of solvent from

higher solvent concentration to
lower solvent concentration
Osmosis
Osmotic Pressure
• Pressure required to stop
osmosis
• depends on the number of
solute particles
Non-electrolytes – molecules
Electrolytes – ions
Solutions to be mixed with body
fluid should have the same
osmotic pressure. WHY?
for greater comfort
efficacy
safety
Body
fluids:
Osmotic
pressure
0.9%
NaCl
• blood solution
• lachrymal fluid
Iso-osmotic
- solutions which have the same
osmotic pressure
- solute can diffuse through
biological membrane
Isotonic
- solutions which have the same
osmotic pressure and tone
- implies biological compatibility
Ex.
1.9% w/v H3BO3 solution
• iso-osmotic with blood and
lachrymal fluid
• isotonic with lachrymal fluid
H3BO3 can pass freely through
the erythrocyte membrane
regardless of concentration which
causes hemolysis.
Solution types relative to a cell:
Isotonic –solute concentration
of solution equal to that of cell
Hypotonic - solute concentration
of solution lower than cell
Hypertonic- solute concentration
of solution higher than of cell
Hemolysis Crenation
 METHODS OF ADJUSTING
SOLUTION TO ISOTONICITY
Class I: (add NaCl)
A. Cryoscopic Method
B. Sodium chloride equivalent Method
Class II: (add water)
A. White-Vincent Method
B. Sprowl’s Method
 Cryoscopic Method

• Freezing point of human blood and

lachrymal fluid = - 0.52°C
• for hypotonic solution (Tf above - 0.52°C);
add therapeutically active solute such as
NaCl, dextrose, KNO3, H3BO3
•For hypertonic solution
(Tf below - 0.52°C);
dilute the solution
 Cryoscopic Method

Procedure:
1. Find the difference between the
freezing point depression (ΔTf or ‘D’ in °C) of
the drug and the body fluid.
2. Calculate the amount of NaCl
needed to render the solution
isotonic based on the ΔTf or ‘D’
of a 0.9% NaCl solution.
 NaCl Equivalent Method

NaCl Equivalent (‘E’)

– the weight in gram of NaCl that will
produce the same osmotic effect as 1 g of
the drug
Ex. E of H3BO3 = 0.52
0.52 g of NaCl will
produce the same osmotic
effect as 1 g of H3BO3
 Calculate the NaCl Equivalent
of a Drug
MW NaCl i subs.
E X
i NaCl MW subs.
KCl is a 2-ion electrolyte dissociating 80% in a
certain concentration. Calculate its dissociation
value (i).
80 K+ ion
80 Cl- ion
20 undissociated particles
180 particles represent 1.8 times as many
particles as there were before dissociation, i = 1.8
ZnCl2 is a 3-ion electrolyte dissociating 80%
in a certain concentration. Calculate its
dissociation value (i).

80 Zn+ + ion
80 Cl- ion
80 Cl- ion
20 undissociated particles
260 particles represent 2.6 times as
many particles as there were before
dissociation, i = 2.6
Dissociation values (i)

Non-electrolytes 1.0

Electrolytes (2 –ion) 1.8

Electrolytes (3 –ion) 2.6

Electrolytes (4 –ion) 3.4

Electrolytes (5 –ion) 4.2

Papaverine HCl (MW 376) is a 2-ion
electrolyte dissociating 80% in a given
concentration. Calculate its NaCl equivalent.
value (i).

MW NaCl i subs.
E X
i NaCl MW subs.
58.5 1.8
E X
1.8 376
E 0.156
 NaCl Equivalent Method
Procedure:
1. Calculate the amount of NaCl represented
by the ingredients in the Rx.
Amount of the ingredient X its E

2. Calculate the amount of NaCl represented

an isotonic solution based on the volume
specified in the Rx.
0.009 X volume of Rx
 NaCl Equivalent Method

3. Calculate the amount of NaCl to be added

to make an isotonic solution.
Step 2 – Step 1
4. If the agent to be used in adjusting the
solution is other than NaCl, divide the
amount of NaCl by the E of the other
substance.

amount of NaCl to be added

E of the other substance
 White - Vincent Method
• involves the addition of water to the drugs
to make an isotonic solution
• followed by the addition of an isotonic or
isotonic-buffered diluting solution to bring
the solution to final volume
• Example of isotonic or isotonic-buffered
diluting solution
Dextrose solution 5.6%
Sodium nitrate solution 1.3%
Isotonic NaCl solution USP
 White - Vincent Method
• Calculate E using Liso
E = 17 (Liso / MW)
• Calculate of the volume of an isotonic solution
V = [∑(W1 X E1)] x v
Where: V = volume of an isotonic solution based on
the amount of drug
W = wt. of drug (g)
E = sodium chloride equivalent of solute
v = 111.1 mL (vol. of a 0.9% NaCl that
contains 1 g of NaCl)
 Sprowls’ Method

• A simplification of White-Vincent Method

where the weight of drug is fixed as 0.3 g
for one fluidounce of a 1% solution

followed by the addition of an isotonic or

isotonic-buffered diluting solution to
bring the solution to final volume
Example of isotonic or isotonic-buffered
diluting solution
Dextrose solution 5.6%
Sodium nitrate solution 1.3%
Isotonic NaCl solution
 Sprowls’ Method
Calculate of the volume of water to dissolve the drug
V = (0.3 g X E1 x v)
Where: V = Sprowl’s value is the V in the White-
Vincent Method
W = wt. of drug (0.3 g)
E = sodium chloride equivalent of solute
v = 111.1 mL (vol. of a 0.9% NaCl that
contains 1 g of NaCl)