Chapter 14:DISPERSE SY

STEMS
DISPERSE SYSTEMS: COMPONENTS
DISPERSED PHASE

The undissolved or immiscible drug (suspen

soid) distributed throughout the liquid vehi
cle. Also called the “internal phase”
DISPERSION MEDIUM

The liquid vehicle, to which the insoluble dr

ug is distributed. Also called “external phase”

Lyophobic is also known as solvent hating, an

d is therefore easily wet by non-polar solvent
than polar solvent or water.
DISPERSE SYSTEMS PARTICLE SIZES
Colloidal dispersions – 1 nm to 0.5 nm
 Coarse dispersions (suspensions and emuls
ions) – 10 um to 50 um
Fine dispersions ( magmas and gels) – 0.5 u
m to 10 um
ACACIA MUCILAGE
May be prepared by placing 350-g of acacia in a gradua
ted bottle, washing with cold purified water and allowi
ng it to drain, add enough warm purified water, in whi
ch 2 g benzoic acid has been dissolved to make the pro
duct measure 1000-ml Therefore the resulting concent
ration will be 35%
By geometric dilution, the potent drug is placed on a
n approximately equal volume of diluent in a mortar &
mixed thoroughly by trituration. Then a second portio
n of diluent equal in volume to the mixture is added an
d the trituration is repeated. This process is continued
by adding equal volume of diluent is incorporated.
SUSPENSIONS
Disperse systems containing finely divided, insoluble
drug particles (“suspensoids’) distributed somewhat u
niformly throughout a liquid vehicle.
 Ready to use liquid form (antacids and analgesics) La
beled as “Oral Suspension”
SUSPENSION
Possible instability phenomena in suspensions:
1. Crystal growth due to hydrate formation
2. The aggregation of particles
3. The creation of a cake that would be difficult to redis
perse
4. The change of viscosity characteristics

 Freeze-thaw cycling technique to stress suspensions f

or stability testing purposes.
Physical
Formulation
stability
Likely physical Effects
instability
problems

Suspensions 1- settling 1-Loss of drug

2- caking content

3- crystal uniformity in

growth different doses

from the bottle
In suspension formulation,
- buffers are used as suspension adjuvants.
- drug substance , antibiotics are active ingredients
- gelatin, veegum, methocel are suspending agents
Packaging Materials
The following problems must be considered from the
stability point of view:
1. Permeability
2. Container sealant integrity
3. Light transmission
4. Interaction between container-closure and product
- leaching & particle release
- sorption
- chemical reactions
REASONS for SUSPENSIONS
For improving product stability
 Ease of administration and flexibility in ad
ministration of a range of doses
Features desired in Pharmaceutical Suspen
sion
1. Particles should settle slowly and should
be readily re-dispersed upon shaking of the
container.
2. The particle size of the suspension shoul
d remain fairly constant throughout long pe
riods of undisturbed standing.
3. The suspension should pour readily and e
venly from its container.
DISPERSED PHASE: PHYSICAL FEATURES
Particle diameter is 1µm to 50µm
Particle size reduction is accomplished by: 
Micropulverization – 10µm-50µm

Fluid energy grinding (jet milling or micron

ization) – under 10 µm
PACKAGING AND STORAGE OF SUSPENSIO
N
packaged in wide-mouth containers having
adequate airspace above the liquid to permit
thorough mixing by shaking and ease of pou
ring
 stored in tight containers protected from fr
eezing, excessive heat, and light.
CAKING = problem usually encountered in suspension

AGITATION = suspension adjunct used to prevent the p

roduct from drying at topical application

Accdg to Stoke’s law, the sedimentation rate of suspensi

on is directly proportional to particle size.

Spray drying technique can produce finely divided parti

cles for suspension formulation.
EXAMPLES OF ORAL SUSPENSIONS

Antacid Oral Suspensions

are intended to counteract the effects of gast

ric hyperacidity and as such are employed by
persons, such as peptic ulcer patients, who
must reduce the level of acidity in the stoma
ch. They are also widely employed and sold
over the counter (OTC) to patients with acid
indigestion, heartburn, and sour stomach.
Antibacterial Oral Suspensions

include preparations of antibiotic substances (e.g., ery

thromycin derivatives, and tetracycline and its derivati
ves), sulfonamides (e.g., sulfamethoxazole and sulfisox
azole acetyl), other anti- infective agents (e.g., methen
amine mandelate and nitrofurantoin), or combination
s of these (e.g., sulfamethoxazole–trimethoprim).
RECTAL SUSPENSIONS
EMULSIONS
A dispersion in which the dispersed phase i
s composed of small globules of liquid distri
buted throughout another liquid, in which i
t is immiscible.
PURPOSE OF EMULSIONS AND OF EMULSIFICATION

Emulsification enables the pharmacist to prepare r

elatively stable and homogeneous mixtures of two
immiscible liquids.
 It permits administration of a liquid drug in the fo
rm of minute globules rather than in bulk.
For orally administered emulsions, the o/w type pe
rmits palatable administration of an otherwise dist
asteful oil by dispersing it in a sweetened, flavored
aqueous vehicle.
Advantages of Emulsions
1. increased therapeutic effects
2. increased spreading ability
3. ability to mask unpleasant odors
TYPES OF EMULSIONS
W/O emulsion - water is the internal phas
e - oil is external phase
 O/W emulsion - oil is the internal phase -
water is external phase
Types emulsion may be tested using the following me
thods:

1. dye solubility test

2. Dilution test
3. Conductivity test
4. UV Fluorescence test
5. Cobalt chloride test
THEORIES OF EMULSIFICATION

SURFACE-TENSION THEORY
ORIENTED WEDGE THEORY
PLASTIC FILM OR INTERFACIAL FILM T
HEORY 
SURFACE-TENSION THEORY

Initially, when oil and water are mixed it bec

omes immiscible due to the presence of surf
ace tension. The use of surfactants result in t
he lowering of interfacial tension between t
wo immiscible liquids.
ORIENTED WEDGE THEORY

This theory assumes monomolecular layers

of emulsifying agent curved around a drople
t of the internal phase.
 PLASTIC FILM OR INTERFACIAL FILM TH
EORY

This theory places the emulsifying agent at the

interface between the oil and water, surroundin
g the droplets of the internal phase as a thin lay
er of film adsorbed on the surface of the drops.
Types of Emulsifiers/Surfactant
s
1. Natural= gelatin, egg yolk, casein, wool fat, cholesterol,
agar, acacia, tragacanth, chondrus, cellulose derivatives.
2. Finely divided = bentonite, MgOH, AlOH, magnesium
trisilicate
3. Synthetic = anionic (sodium lauryl sulfate), cationic (b
enzalkonium chloride), nonionic (sorbitan fatty acid este
rs such as Span and Tweens)
SPANS – are resistant to addition of acids and electrolytes;
hydrophobic (low HLB value) or lipophilic; and they for
m w/o emulsion
The HLB System

HYDROPHILE – LIPOPHILE BALANCE

Used to classify non-ionic surfactant.
All NON –IONIC surfactants have an HLB value. The
higher the HLB number, the more hydrophilic. The lo
wer the HLB number, the more lipophilic
Application of Surfactants HLB VALUE SURFACT
ANT RANGE APPLICATION

1–3 Antifoaming agents

3–6 Water-in-Oil emulsifiers
7–9 Wetting agents
8 – 18 Oil-in-Water emulsifiers
13 – 16 Detergents
 15 – 20 Solubilizing agents
Addition of antifoaming agent and application of compr
essed air will break up the foam in emulsion producin
g a smooth emulsion.

To increase the viscosity of the aqueous phase of an emu

lsion, there is a need to add dissolved micromolecules.
Methods of Emulsion Preparation
 WET GUM METHOD (English method) 4:2:1 of
oil : water : gum Formation of Primary Gum as the
nucleus of the emulsion.
 DRY GUM METHOD (Continental method) 4:
2:1 ratio of oil: water: gum Formation of Primary M
ucilage as the nucleus of the emulsion
BOTTLE METHOD (Forbes Bottle method) 2:2
: 1 ratio of oil : water : gum Applicable to emulsions
containing Volatile Oils. eg. Preparing emulsion us
ing volatile oil is added to acacia in a bottle.
MICROEMULSION
Thermodynamically stable system

Optically transparent isotropic mixture of a

biphasic O/W system stabilized with surfact
ants
Diameter of particle: 100 Å (10 mμ) to 1000
Å (Angstrom)
EXAMPLES OF ORAL EMULSIONS
MINERAL OIL EMULSION OR LIQUID
PETROLATUM EMULSION
>prepared by dry gum method

>employed as lubricating agents with 30ml

dose

Mineral oil is a common levigating agent

CASTOR OIL EMULSION
Castor oil emulsion is used as a laxative for i
solated bouts of constipation and in prepara
tion of the colon for radiography and endosc
opic examination. 
 the adult dose is 45 mL, about three tables
poonfuls. For children 2 to 6 years of age, 15
mL is usually sufficient, and for children less
than 2 years of age, 5 mL may be given.
Simethicone Emulsion
Simethicone emulsion is a water-dispersible
form of simethicone used as a defoaming ag
ent for the relief of painful symptoms of exc
essive gas in the gastrointestinal tract.
The emulsion in drop form is useful for reli
ef of gas in infants due to colic, air swallowin
g, or lactose intolerance. 
Topical Emulsion
Use to treat dry skin are o/w emulsion
A number of topical emulsions, or lotions a
re used therapeutically to deliver a drug syst
emically.
The physical stability of emulsion
and suspension can be influenzed b
y factors affecting the chemical sta
bility of excipients such as emulsifi
ers, suspending agents, antioxidant
s, etc.
During storage the instability of a
n emulsion is evidenced by the ff p
henomena: creaming, reversible ag
gregation (flocculation) and irrever
sible aggregation (coalescence)
Creaming – is the upward motion of aggregates or glo
bules to rise to the top of the emulsion.
Flocculation refers to the rapid formation of emulsion
droplets or aggregates due the absence of a protective
barrier at the oil-water interface and insufficient emuls
ifier surface coverage. Or it is the aggregation of the dis
persed globules into loose clusters within the emulsio
n. . It is the phenomenon applied to solid surfaces.
Cracking – the coalescence of oil globules in o/w emul
sion
EMULSION
PROBLEM REMEDIES
1. Creaming - Reconstituted by shaking or mixing
2. Flocculation
3. Coalescence
- Used of accelerated test methods such as exposure t
o:
a. elevated temperature
b. freeze-thaw cycles (temp cycling)
c. shaking tests
d. ultracentrifugation
Physical
Formulation
stability
Likely physical Effects
instability
problems

Emulsions 1- Creaming 1- Loss of drug

2- coalescence content
uniformity in
different doses
from the bottle