CHAPTER 14: DISPERSED SYSTEM

Dispersed phase - It consists of dispersed phase and dispersion

medium and are usually solid materials that are insoluble in the
dispersion medium.
• Particles of dispersed phase vary in size – 0.5µm to 10 µm –
fine dispersion – 1nm - 0.5µm colloidal dispersion – > 0.5 µm
coarse dispersion (usually 10-50µm susp & emulsion)
• In the case of emulsions, the dispersed phase is a liquid that is
neither soluble nor miscible with the liquid of the dispersing
phase.
• Emulsification - results in the dispersion of liquid drug as fine
droplets throughout the dispersing phase.
• Aerosol - the dispersed phase may be small air bubbles
throughout a solution or an emulsion.
• Dispersions - also consist of droplets of a liquid (solution or
suspension) in air.
• Coarse Dispersion - dispersions containing coarse particles,
usually 10 to 50 µm
• Fine Dispersions - dispersions containing particles of smaller
size are termed
• Colloidal Dispersions - if the particles are in the colloidal
range.
• greater size, particles in a coarse dispersion have a greater
tendency to separate from the dispersion
• Most solids in dispersion tend to settle to the bottom of the
container because of their greater density.

Molecule - is the smallest unit of any chemical compound that

possesses all the native properties of that compound

Dissolution - is the solid to liquid transformation that converts

solid drug particles to individual, dissolved liquid molecules.

SUSPENSIONS

• Refers to a two-phase system consisting of a finely divided

solid dispersed (suspended) in a liquid (the dispersing
medium).
• Preparations containing finely divided drug particles (the
suspensoid) distributed somewhat uniformly throughout a
vehicle in which the drug exhibits a minimum degree of
solubility
• It is a disperse system in which solid, vehicle-insoluble
particles (internal phase) are uniformly suspended by
mechanical agitation and formulation design throughout the
liquid vehicle (external phase).
• The solid particles is greater than 1um.
• Most good pharmaceutical suspensions = 1 to 50 µm
CLASSIFICATION OF SUSPENSION:
According to route of administration:
Oral suspensions
Topical /External suspensions
Parenteral suspension

ADVANTAGES:
Provide palatable mixtures of an insoluble derivative of a
drug that in its soluble form has a highly unpleasant taste
Prolongs the action of drug
Chemical stability
Ease of swallowing
Flexibility of doses

PROPERTIES DESIRED IN PHARMACEUTICAL

SUSPENSION
Settle slowly and should be readily redispersed upon
gentle shaking
particles size should remain fairly constant throughout
long periods of undisturbed standing
Pour readily and evenly from its container

SEDIMENTATION AND STROKES LAW

• The Stokes equation was derived for an

ideal situation in which uniform, perfectly
spherical particles in a very dilute suspension settle without
producing turbulence
• the basic concepts of the equation
do give a valid indication of the factors that
are important to suspension of the particles
and a clue to the possible adjustments that
can be made to a formulation to decrease the
rate of sedimentation

• Reducing the particle size of the dispersed phase produces a

slower rate of descent of the particles. Also, the greater the
density of the particles, the greater the rate of descent.
• If the particles were less dense than the vehicle, they would
tend to float, and floating particles would be quite difficult to
distribute uniformly in the vehicle.
• The rate of sedimentation may be appreciably reduced by
increasing the viscosity of the dispersion medium.
• The viscosity characteristics of a suspension may be altered
not only by the vehicle
used but also by the solid content. As the
proportion of solid particles in a suspension
increases, so does the viscosity.

VISCOMETER

• Particularly, Brookfield viscometer, which measures viscosity

by the force required to rotate a spindle in the fluid being
tested
• In most good pharmaceutical suspensions, the particle
diameter is 1 to 50 µm.
• One of the most rapid, convenient, and inexpensive methods
of producing fine drug powders of about 10 to 50 µm size is
micropulverization. (dry milling)
• Finer: < 10 um by fluid energy grinding is
Jet milling. l For parenteral or ophthalmic suspension)
• Spray drying – extremely small dimensions
Small particles reduces sedimentation rate but may pose a
problem on forming hard sediment.

MICROPULVERIZATION

• Micropulverizers are high-speed attrition or impact mills that

are efficient in reducing powders to the size acceptable for most
oral and topical suspensions.
• For still finer particles, under 10 µm, fluid
energy grinding, sometimes referred to as jet milling or
micronizing, is quite effective.
• In jet milling, the shearing action of high
velocity compressed airstreams on the particles in a confined
space produces the desired ultrafine or micronized particles. The
particles to be micronized are swept into violent turbulence by
the sonic and supersonic
velocities of the airstreams.
• Particles of extremely small dimensions may
also be produced by spray drying. A spray dryer is a cone-
shaped apparatus into which a solution of a drug is sprayed and
rapidly dried by a current of warm, dry air circulating in the
cone.
• However, one should avoid reducing the
particle size too much because fine particles have a tendency to
form a compact cake upon settling to the bottom of the
container. The result may be that the cake resists breakup.
• The particle shape of the suspensoid can
also affect caking and product stability. It has been shown that
symmetrical barrel-shaped particles of calcium carbonate
produced more stable suspensions than did asymmetrical needle-
shaped particles of the same agent.
• To avoid formation of a cake, it is necessary
to prevent agglomeration of the particles into larger crystals or
into masses.

FLOCS/FLOCCULE
• an aggregation of particles
• Form loose aggregate
• Rate of sedimentation is high
• Sedimentation volume is high à somewhat unsightly
• Sediment is formed rapidly
• Sediment is loosely packed
• AVOIDS the problem of CAKING
• clays such as diluted bentonite magma are an flocculating
agent.
• Electrolytes can also act as flocculating
agents, apparently by reducing the electrical barrier between the
particles of the suspensoid and forming a bridge so as to link
them together.
• surface-active agents (surfactants) can also
induce flocculation of particles in suspension and increase the
sedimentation volume.

Flocculating agents
Bentonite, MC, sodium
alginate, tragacanth,
pH adjustment
Electrolytes
Surfactants

DISPERSION MEDIUM
• Density of the suspensoid
• If suspensoid is flocculated
• Amount of the suspensoid
• Use of suspending agents
(MC, CMC, MCC,PVP, xanthan gum and bentonite) at
concentrations of 0.5% to 5%
• Apply Rheology - the study of flow, addresses
the viscosity characteristics of powders, fluids, and semisolids.

COMPONENTS OF A SUSPENSION:
Flocculating agents- enhance particle “dispersability”
Viscosity enhancers- reduce sedimentation
rate in the flocculated suspension (Hydroxypropylcellulose,
Hydroxypropyl methylcellulose)
Preservatives- prevents the growth of
microorganisms (Benzoic acid, Methyl
Paraben)
Stabilizers- any additive used in substance
and compounds to keep them stable, retard
deterioration
Wetting agents - increases penetration by
the dispersion medium (Alcohol, glycerin,
propylene glycol, and other hygroscopic
liquids.

PREPARATION OF SUSPENSION:
Wet the powders using wetting agents like
alcohol, glycerin, propylene glycol and other
hygroscopic agents
Use colloid mills or mortar and pestle to
effect thorough mixing
Add the dispersion medium to which other
soluble components are dissolved

EXTEMPORANEOUS PREPARATION

Capsules or tablets are place in mortar and

pestle
Vehicle is added and mixed thoroughly to
create a paste
Diluted to volume using desired vehicle
Caution on the use of alcohol, Benzyl
alcohol and Propylene glycol on neonates
and geriatric patients
• International Journal of Pharmaceutical Compounding -
hundreds of compounded liquid formulations are available
through journals
• It is known that drugs in liquid form have
faster decomposition rates than in solid form and some are
affected by the pH of the medium.
• Leucovorin calcium when compounded
from crushed tablets or the injectable form is most stable in milk
or antacid and is unstable in acidic solutions.
• The selected vehicle can be a commercial
product, such as the Ora family of preparations (Ora-Sweet,
Ora-Sweet SF, Ora-Plus, Ora-Blend, Paddock Laboratories).
• In the neonate, alcohol can alter liver
function, cause gastric irritation, and effect neurologic
depression.
• To minimize stability problems of the
extemporaneous product, it should be placed in an airtight, light-
resistant container and stored in the ref by patients

PACKAGING AND STORAGE

• Wide-mouth
• Tight containers
• Protected from freezing, excessive heat &light
• Shake well instruction
• Antacid oral suspensions, antibacterials,
antiprotozoal and anti-inflammatatory

Other examples:
Rectal suspensions: Barium sulfate for suspension,
Mesalamine, Colocort
Dry powders for suspension – “for oral suspension”

Antacid Oral Suspension

• Antacids are intended to counteract the
effects of gastric hyperacidity and, as such, are employed by
persons, such as peptic ulcer patients, who must reduce the level
of acidity in the stomach.
• They are also widely employed and sold over
the counter (OTC) to patients with acid indigestion and
heartburn.
• Most antacid preparations are composed
of water-insoluble materials that act within the gastrointestinal
tract to counteract the acid.
• A few water-soluble agents are employed;
including aluminum hydroxide, aluminum phosphate,
dihydroxyaluminum aminoacetate, calcium carbonate, calcium
phosphate, magaldrate, magnesium carbonate, magnesium
oxide, and magnesium hydroxide.

EMULSION
• A thermodynamically unstable two-phase
system consisting of at least two immiscible
liquids, one of which is dispersed in the form
of small droplets throughout the other, and
an emulsifying agent.