codSURFACE AND INTERFACIAL PHENOMENA 1.

The higher the HLB number, the more

hydrophilic is the surfactant
INTERFACIAL SURFACE 2. The lower the HLB number, the more
 The boundary that keeps the two phase apart lipophilic is the surfactant
 Surface – used instead when one of the two 3. Exceptions to HLB scale – sodium lauryl
phases is a gas or a vapor sulfate with an HLB value of 40

HYDROPHILIC–LIPOPHILIC BALANCE
15-18 Solubilizing agents Sodium lauryl sulphate
 The molecules at the interface possess a 13-15 Detergents Sodium Stearate
positive free energy (higher energy state) 8-16 O/W emulsifying agents Tween
 Over time, this free energy decreases resulting 7-9 Wetting agents Acacia
in separation 3-6 W/O emulsifying agents Span
 Surfactant / surface-active agents 1-3 Antifoaming agents Simethicone
- Prevents separation of the molecules at the
interface METHODS OF IP OR ST DETERMINATION

INTERFACES OF PHARMACEUTICAL INTEREST  DROP WEIGHT METHOD

 Liquid/Solid system - Principle: if a liquid is allowed slowly
- Suspensions through a capillary tube, the liquid first
forms a drop at the tip of the capillary tube,
 Liquid/Liquid system which gradually increases in size and finally
- Emulsions detaches when the weight of the drop (W)
equals to the surface tension at the
 Vapor/Liquid systems circumference of the tube (2 π ry)
- Foams W =2 πry
- The surface tension the liquid can be
INTERFACIAL TENSION determined by either (1) the drop weight
 Force per unit length existing at the interface method or (2) the drop count method using
between two immiscible liquid phases stalagmometer
 Unit: dynes/cm

SURFACE TENSION  CAPILLARY RISE METHOD

 Force per unit length that must be applied - Most accurate
parallel to the surface so as to counterbalance - Not suitable for interfacial surface
the net inward pull - capillary tube
 Unit: dynes/cm
 DU NOUY RING METHOD
FACTORS AFFECTING SURFACE TENSION - Du Nuoy Tensiometer
 Temperature
- Increase temperature; ST decrease;  BUBBLE PRESSURE
solubility increases  WILHELMY PLATE
 OSCILLATING DROP
 Surfactants  RENDANT DROP
- Move to the interface thereby decrease  SESSILE DROP
surface tension
- Based on HLB table SURFACTANTS
- Based on chemical structure  Substances having both hydrophilic or
hydrophobic regions in their molecular
HYDROPHILIC–LIPOPHILIC BALANCE structure
 Introduced by Griffin in 1947  Addition of surfactants lower interfacial and
surface tension, increasing solubility

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  Beyond saturation of surfactants lead to
formation of micelles (helps in solubility)
CRITICAL MICELLE CONCENTRATION
 The concentration at which micelle formation
occurs
 As the concentration of surfactant is increased
above CMC:
1. Colligative properties
POLYMERS
 Polymer – “many parts”
 A large molecule composed of many small
repeating units
POLYMERS vs. MACROMOLECULES
 Macromolecules – coined by Herman
Staudinger in 1953
 The difference between macromolecules and
polymers is that macromolecules are made up
of not necessarily repeating units
 Polymers are subset of macromolecules
CLASSIFICATIONS OF SURFACTANTS
1. ANIONIC SURFACTANTS
 Consists of the soaps of alkali, amines and
metals, sulfated alcohols and sulfonates
 The long-chain anion (negative charge) imparts
surface activity, the cation parts is inactive
 Not suitable for internal use because of their
unpleasant taste and irritant action on intestinal
mucosa
Alkali soaps (sodium and potassium stearate)
1.sodium, potassium and ammonium salts of
long –chain fatty acids (stearic acid and oleic
acid)
2.unstable below pH 10 and are incompatible
with acids and polyvalent inorganic and long-
chain fatty acids
Metallic soaps (calcium stearate)
1.salts of divalent and trivalent metals (calcium,
magnesium, zinc and aluminum)
Amine soaps
1.Formed by reaction between amines
(ethanolamine, diethanolamine and
triethanolamine) and fatty acids (oleic acid)
Alkyl Sulphates and Phosphates (sodium lauryl sulphate)
1.Esters formed by reaction of fatty alcohols
with sulphuric acid and phosphoric acid
Alkyl Sulphonates (Sodium dioctyl Sulphosuccinate also
known as Aerosol acid)
1.Effective wetting agent
2. CATIONIC SURFCTANTS
 In aqueous solutions, they dissociated to form
positively charged cations, which gives them
emulsifying properties
 Ex. quaternary ammonium compounds –
cetyltrimetylammonium bromide (cetrimide),
benzethonium chloride and benzalkonium
chloride
a. More popular as antiseptics or disinfecting
agents (bactericidal action)
b. Widely used as preservatives and for
sterilizing contaminated surfaces
c. Secondary emulsifying agents for external
application
d. Incompatible with anionic surfactants and
unstable at high pH
3. AMPHOLYTICS SURFACTANTS
 Possess both cationic and anionic groups in the
same molecule and their ionic characteristics
depend on the pH of the system
- Low pH – cations
- High pH – anions
- Intermediate pH – twitterions
 Ex. Lecithin and N-dodecyl alanine
4. NONIONIC SURFACTANTS
 Useful for oral and parenteral formulations (low
irritation and low toxicity)
 Less sensitive in the changes of pH of the
medium and the presence of electrolytes
 Sorbitan esters (Spans)
∙ stabilizes water in oil (w/o) emulsions
∙ Products of the esterification of
sorbitan with fatty acid
∙ Low HLB number, insoluble in water
and used as W/O emulsifier
 Polysorbates (Tweens)
∙ stabilizes oil in water (o/w) emulsions
∙ ethoxylated derivatives of sorbitan
esters
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 ∙ high HLB number, soluble in water and
used as O/W emulsifiers
5. POLYMERIC SURFACTANTS
 Common examples is the A-B-A blocks
copolymers
 A being the hydrophilic chain [poly(ethylene
oxide), PEO]
 B being the hydrophobic chain [poly(propylene
oxide), PPO]
APPLICATION OF SURFACTANTS
MEDICINAL APPLICATIONS
 AS ANTIMICROBIALS: Cationic surfactants such
as cetrimide and benzalkonium chloride have
useful antibacterial properties. They are used as
disinfectants for instruments and as an
antiseptic for the skin. These surfactants adsorb
over the surface of the bacterial cell (Gram-
negative bacteria) owing to their positive
charge. This changes the cell membrane
permeability, resulting in loss of essential
substances from the cell, in turn resulting in its
death.
 AS EXPECTORANTS: In acute and chronic inf. Of
the upper respiratory tract (e.g. bronchitis,
asthma and TB), the viscosity of bronchial
mucus increases. The mucus dries out, which
causes difficulty in breathing. Inhalation of
sprays or mists (aerosols) containing
surfactants, such as calfactants, loosens the
mucus and results in its easy removal, thereby
providing relief.
 AS CLEANING AGENTS: Since surfactants have
detergent properties, these are also used as
cleansing agents. However, their repeated use
should be avoided since this may cause
irritation of the skin. Ex of surfactants used as
cleansing agents include ammonium lauryl
sulphate
PHARMACEUTICAL APPLICATIONS
 AS SOLUBILIZING AGENTS: Surfactants have
been extensively used as solubilizing agent for
number of poorly soluble drugs such as oil-
soluble vitamins, volatile oils, hormones,
phenobarbitone and sulphonamides. Oil-soluble
vitamins such as vitamin A are unpleasant to
take in the form of fish live oil but are easily
palatable when administered in the form of oil
in water or as solubilized system in water. Such
solubilized systems are more resistant to
oxidation than either oily solutions or
emulsions. Surfactants have also been used to
solubilize many disinfectant compounds such as
cresol and chloroxylenol. Lysol, which is a
solution of phenol and alkali soap in water, is a
very good disinfectant. The disinfectant
property of the compound is increased by the
use of surfactants since they also alter the
permeability of the cell membrane of
microorganisms.
 AS WETTING AGENTS: Their hydrophobic
nature makes them aggregate and agglomerate
when added to water. Dispersions containing
such hydrophobic powders are often difficult to
prepare since the powders from large floccules
or float on the surface, thereby hindering the
preparation of uniform suspension. This can be
solved by the use of surfactants, which get
adsorbed at the solid/liquid interface and
increase the affinity of the hydrophobic powder
for water while reducing the attractive forces
between particles of the solid. Aerosol OT is a
very good example of wetting agent.
 AS FLOCCULATING AGENTS: Use of surfactants
coupled with the precipitation results in the
desirable action of controlled flocculation in
suspensions. For example, sulphamerazine, a
hydrophobic powder, can be dispersed by
means of aerosol OT in association with
aluminum ions. Although these flocculated
particles settle on standing, they do not form a
hard cake easily disperse in the vehicle on
shaking.
 AS ADDITIVES IN SEMISOLID PREPARATIONS:
Surfactants are often added to creams and
ointments to alter the release characteristics of
the incorporated drug. The release rate may be
accelerated because of the absorption of water
from the surrounding environment. Further, the
capacity of different ointment bases to take up
aqueous liquids can also be improved by the
addition of surfactants
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RHEOLOGY  Pseudoplastic
 Deals with the deformation and flow properties - Shear-thinning
of matter - There is no yield value
 “rheo” – to flow - Apparent viscosity decreases with an
 “logos” – study/science increase n the rate of shear
- Eg. Polymer solutions, liquid dispersion of
VISCOSITY tragacanth, sodium alginate,
 Resistance to flow methylcellulose and sodium CMC

FLUIDITY  Dilatant
 Ability to flow - Shear-thickening
- Apparent viscosity increases with increase
3 WAYS TO EXPRESS VISCOSITY in the rate of shear (such systems increase
in volume when sheared)
 Absolute viscosity
- No std used in the determination  Shear-dependent
- Unit: poise Plastic
- Measure of the resistance to flow of a fluid - Aka bingham bodies
under an applied force - Show no apparent response to low-level
stress
 Kinematic viscosity - Flow begins only after a limiting yield stress
- Type of absolute viscosity (yield value) is exceeded
- Related to absolute viscosity as a function - Eg. Flocculated particles in concentration
of the fluid’s specific gravity
- Unit: stokes Plasticity
- SUS – saybolt universal seconds - elastic
- Ratio of the absolute viscosity of the sample - Free flowing
to the density of the sample
 Time dependent
 Relative viscosity
- It is the ratio of the viscosity of a solution to Thixotropy
the viscosity of the solvent used - An isothermal and comparatively slow
- It is the ratio of the viscosity of the sample recovery of a consistency lost through
to the viscosity of the water shearing
- Unit: - Materials which become less viscous
overtime when shaken, agitated or stressed
NEWTON’S LAW OF FLOW
 The higher the viscosity of the sample, the Rheopectic
greater is the shearing stress (F) necessary to be - Materials which become more viscous
applied in order to produce a certain rate of overtime when shaken, agitated or stressed
shear gradient (G)
VISCOMETERS
2 classification 2 TYPES
 Newtonian  Single point
- Obeys the Newton’s law of flow - Capillary – capillary tube
- Ex. simple liquids like water ∙ Ostwald viscosity
- Falling sphere – ball bearing (glass or steel)
 Non-newtonian ∙ Hoeppler viscosity
- Don’t obey the newton’s law of flow, exhibit  Multipoint
either shear-dependent or time-dependent - Cup and bob viscosity
viscosity ∙ Coutte
 Cup rotates

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  Mac Michael viscosity through filter Suspensions,
paper RBC
∙ Searle
Don’t diffuse
 Bob rotates
 Rotavisco, Stormer,
Brookfield ATTRACTION BETWEEN THE DISPERSED PHASE AND
- Cone and plate THE DISPERSION MEDIUM
∙ Ferranti Shirley Viscosity
∙ Cone rotates SOLVATION
• Attachment of solvent molecules to the
molecules of the dispersed phase

HYDRATION
• Water is the dispersion medium

DISPERSED SYSTEMS
 Consists of a dispersed phase in a dispersion
medium TYPES OF COLLOIDAL DISPERSION
DISPERSIO DISPERSE COLLOID EXAMPLES
CLASSIFICATIONS N D PHASE TYPE
 Molecular dispersion MEDIUM
 Colloidal dispersion
 Coarse dispersion SOLID SOLID SOLID PEARLS,
SOLID LIQUID SOL OPALS
Classification of Dispersed Systems on the Basis of SOLID GAS SOLID CHEESE
Particle Size LIQUID SOLID EMULSIO BUTTER
LIQUID LIQUID N PUMICE
CLASS RANGE CHARACTERISTICS EXAMPLES LIQUID GAS SOLID MARSHMALLO
OF OF A SYSTEM GAS SOLID FOAM W
PARTICLE GAS LIQUID SOL, GEL JELLY, PAINT
SIZE EMULSIO MILK,
N MAYONNAISE
MOLECULA Less than Invisible in Oxygen
FOAM WHIPPED
R 1.0 nm electron molecules
SOLID CREAM
DISPERSION microscope Ions
AEROSOL SMOKE, DUST
Pass through Glucose
S CLOUDS,
semi-permeable
LIQUID MIST, FOG
membrane
AEROSOL
Rapid diffusion
S
COLLOIDAL 1.0 nm Visible in electron Colloidal
DISOERSION to 0.5 microscope silver sols
um Pass through Natural and TYPES OF COLLOIDAL SYSTEMS
filter paper synthetic
Slowly diffuse polymers LYOPHILIC COLLOIDS
 Systems containing colloidal particles that
COARSE Greater Visible under Grains of interact to an appreciable extent with the
DISPERSION than 0.5 microscope sand dispersion medium
um Don’t pass Emulsion

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LYOPHOBIC COLLOIDS
 Composed of materials that have little
attraction for the dispersion medium because of
the absence of a solvent sheath around the
particle

SPECIAL METHODS TO PREPARE LYOPHOBIC COLLOIDS

 DISPERSION METHODS
• Coarse particles are reduced in size
• High intensity ultrasonic generator, colloid mills

 CONDENSATION METHODS
Brownian Movement
• Materials of subcolloidal dimensions are caused
- Random/zigzag movement (no uniform
to aggregate into particles within the colloidal
movement)
size range
- Counteracts sedimentation to a measurable
• Redox rxn, supersaturation, hydrolysis, double
extent at room temperature by keeping the
decomposition
ASSOCIATION/AMPHIPHILIC COLLOIDS dispersed material in random motion
 Characterized by having two distinct regions of
opposing solution affinities with the same
molecule or ion Sedimentation
- Can be expressed using Stoke’s law
- d 2=¿ ¿

OPTICAL PROPERTIES OF COLLOIDS g = acceleration during gravity

• THE FARADAY – TYNDALL EFFECT
- Appearance of Tyndall cone
- Can be seen using ultra microscope
• ELECTRON MICROSCOPE
- Commonly used in capturing or yielding of
the _________ particles of the colloids
• LIGHT SCATTERING
- Property of scatter light
- Can be expressed by measuring of solid
turbidity
A given cone of disperse phase
The turbidity is proportional to the lyophilic
phase
d = diameter of particles
η = viscosity
What is the sedimentation rate (in cgs units) of a
suspension with spherical particles in water if the (a) the
diameter and density of the powder are 5μm and 1.33
g/cm3, respectively (the viscosity od water is 0.9 cP); (b)
the diameter of the powder is reduced to 1 μm; and (c)
the viscosity is increased to 4.5 cp while maintaining the
particles at 5 μm?

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