Coarse Dispersion

Chapter 8

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Outline
 Introduction
 Suspension
 Introduction
 Settling of Suspension
 Formulation
 Emulsion
 Theories of Emulsification
 Pharmaceutical Applications
 Microemulsions
 Semisolids
 Classification of Semi-solids

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 Introduction
 Solute does not completely dissolve in solvent and may
be visible in naked eye
 Size 10mcm-50mcm
 Examples are suspensions, emulsions, foams, aerosols

Dispersed phase In solid In Liquid In Gas

Solid Paste Suspension Solid Aerosol
Liquid Solid Emulsion Emulsion Liquid Aerosol
Gas Solid Foam Foam Nil

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Introduction
 Colloidal dispersion have much higher surface area
compared to coarse dispersion
 For undissolved solid in liquid dispersion, the solid
particles have a greater density than the dispersing
medium and thus tend to settle under the influence of
gravity
 For undissolved liquid in coarse dispersion, the dispersed
phase tend to separate as the top layer, also as a result of
differential density and gravity

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Types of Coarse Dispersions
 In preparing suspensions, particle-particle attractive forces
need to be overcome by high shearing action of such devices
as the colloid mill, or by use of surface active agents.
 The latter greatly facilitate wetting of the lyophobic powders
and assist in the removal of surface air that shearing alone
may not remove; thus the clumping tendency of particles is
reduced.
 Lowering of surface free energy by the adsorption of these
agents directly reduces the thermodynamic driving force
opposing dispersion of the particles
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Types of Coarse Dispersions
 In emulsification, shear rates at frequently necessary for
dispersion of the internal phase into fine droplets, the shear
forces are opposed by forces operating to resist distortion and
subsequent breakup of the droplets.
 Again surface active agents help greatly by lowering
interfacial tension, which is primarily reversible component
resisting droplet distortion.
 Surface active agents may also play an important role in
determining whether an oil-in-water (o/w) or water-in-oil
(w/o) emulsion preferentially survives the shearing action
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SUSPENSION
 A preparation containing finely divided drug particles
(suspensoid) distributed uniformly throughout a vehicle in
which exhibits a minimum degree of solubility
 Types:
1. Ready to use form
 Suspension already distributed to a vehicle with or without
additives
 Designated as drug oral suspension
2. 2. Dry powders or mixtures for reconstitution
 Suspension, which generally contains a powder mixture of drug
and other excipients
 Designated as drug for oral suspension

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SUSPENSION
 Properties of a good suspension:
1. Slow sedimentation rate
2. Resuspendable or Redispersable
3. Pourable
4. Particle size of suspensoid should remain fairly constant
 Suspending agents
 substances added to the dispersion medium to modify the
vehicle viscosity and assist in the suspension of the suspensoids
and slow down the sedimentation rate

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SUSPENSION
 Categories of Suspending agents
Natural polysaccharides Semi synthetic polysaccharides
• Ex. Starch, acacia • Ex. Methylcellulose,
microcrystalline cellulose
Clays (inorganic hydrated Synthetic thickeners
silicates • Carbomer, polyvinyl alcohol
• Ex. Bentonite, talc
Miscellaneous
• Ex. Gelatin

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Kinds of Suspension
 Gels
 Semi solid systems containing of dispersions made up of either
small inorganic particles of large organic molecules enclosing
and interpenetrating by a liquid
 Properties:
 Inhibition- taking up of liquid without increase in volume
 Swelling – taking up of liquid with increase in volume
 Syneresis – gel shrinking due to separation of dispersion
medium
 Thixotrophy – a reversible gel – solution formation

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Kinds of Suspension
 Lotions
 Are liquid suspensions or dispersions intented for external
application to the body
 Methods of preparation:
 Trituration
 Precipitation
 Lotion are usually applied without friction

 Magmas and milk

 Are aqueous suspensions of insoluble, inorganic drugs
 Thick and viscous, should be provided with a shake well label
 Freezing must be avoided

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Kinds of Suspension
 Mixtures
 Are aqueous liquid preparations which contain suspended,
insoluble solid substances and are intended for internal use
 Insoluble substances must be in finely divided state – using
colloids

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Settling in Suspension
 Theory of Sedimentation by _____
 dilute suspensions – free settling
 high concentration of dispersed phase 95%, 10%) – hindered
settling
 Effect of Brownian Movement
 with suspending agents, less Brownian movement
 Sedimentation of Flocculated Particles
 Difference between flocculated and deflocculated suspension
 Initial rate of settling of flocculated particles is determined by
floc size and porosity of aggregated mass

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Formulation of Suspension
Wetting of Particles
 Powdered substance is not readily wetted, although high
density, it FLOATS on the surface of liquids
 HYDROPHOBIC (High contact angle with water): Ex-
sulfur, charcoal
 HYDROPHILIC (low or zero contact angle with water):
Ex – talc, zinc oxide
 Surfactants are added to reduce interfacial tension
between solid particles and vehicle  wetting (increase
contact angle) deflocculation
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Formulation of Suspension
Controlled Flocculation
 How to control flocculation to prevent formation of
compact sediment that is difficult to redisperse?
 FLOCCULATING AGENTS
 ELECTROLYTES – reduce electric barrier between particles
to link them together in loosely arranged structure
Ex: monobasic potassium phosphate
 SURFACTANTS– ionic and nonionic; take note on the
concentration

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Formulation of Suspension
 FLOCCULATING AGENTS
 POLYMERS – long chain, high MW compounds containing
active groups spaced along their length
- part of the long chain is adsorbed on the particle surface and
remaining part on the dispersion medium  bridge between
dispersion will lead to formation of flocs
- Ex: bismuth subcarbonate

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Formulation of Suspension
Rheologic Considerations
 application of rheology in suspension:

viscosity of suspension affecting particle settling

change in flow properties of suspension when container

is shaken and poured from the bottle

spreading qualities of the lotion when it is applied to an

affected area
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Formulation of Suspension
Rheologic Considerations
 In manufacturing suspension, IDEAL suspending agent
should have: HIGH viscosity at negligible shear (during
storage) and LOW viscosity at high shearing rates (free-
flowing during agitation, pouring and spreading)

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EMULSION
 a heterogeneous system made up of 2 immiscible liquids
 a dispersion in which the dispersed phase is composed of
small globules of a liquid distributed throughout a
vehicle in which it is immiscible
Internal phase External phase Emulsifying agent

• discontinuous • continuous • lowers

phase phase interfacial
• dispersed • dispersing tension
phase medium
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EMULSION
 Qualities of emulsifying agents:
 compatible with other formulative ingredients
 stable
 non toxic
 conductivity test
 lightning of the bulb – (o/w)

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Theories of Emulsification
1. Surface tension theory
 emulsifiers tend to lower interfacial tension by reducing
the repellent force between liquids and diminishing each
liquids attraction for its own molecules
2. Oriented wedge theory
 emulsifiers tend to orient themselves in a liquid in
manner reflective of their solubility, the phase in which
the emulsifier in more soluble become the external phase

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Emulsion-Pharmaceutical Applications
 An o/w emulsion is a convenient means of orally
administering water insoluble liquids, especially when the
dispersed phase has an unpleasant taste
 The use of IV emulsion as a means of maintaining debilitated
patients who are unable to assimilate materials administered
orally
 When the emulsion is administered IV, the droplets are normally
rapidly taken up by the cells of the reticuloendothelial system
 Emulsification is widely used in pharmaceutical and
cosmetic products for external use
 Emulsification is used in aerosol products to produce foam

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Emulsion instability an be:
flocculation or coalescence or
creaming – breaking –
reversible irreversible

miscellaneous
physical and phase inversion
chemical changes
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Microemulsions
 Consist of large swollen micelles containing the internal
phase, much like that found in a solubilized solution
 They appear as clear transparent solution, but unlike
micellar solubilized system, microemulsions may not be
thermodynamically stable
 Contain droplets of oil in water (o/w) or droplets of water
in oil (w/o) with diameters of 10-20 nm and the volume
fraction of the dispersed phase varies from 0.2-0.8

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Microemulsions
 The droplet average molecular weight can be measured
by light scattering technique
 Microemulsions can be used to increase bioavailability of
drugs poorly soluble in water by the incorporation of
drug into internal phase
 Also been considered as topical drug delivery system
 Presently used in cosmetic science, foods, dry cleaning,
and wax polishing products

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SEMISOLIDS
A. Gels
 semi solid systems of at least 2 constituents
 Condensed mass enclosed – external phase
 Interpenetrated liquid – internal phase

 Jelly – when the coherent matrix is rich in liquid

 Ex. Ephedrine sulfate jelly
 Xerogel – when gels liquids removed and only the framework
remains
 Ex. Gelatin sheets, tragacanth ribbons, acacia tears

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SEMISOLIDS
 Classification of gels
1. Two-phase system
 a gel mass consist of a network of small discrete particles or floccules
 magma – if the particle size of dispersed phase is relatively large
 ex. Aluminum magma, bentonite magma, magnesia magma
 inorganic gels
 thixotropic gel-sol formation
2. Basic phase system
 macromolecule existing as twisted matted strands
 often bound by van der waals forces to form crystalline and amorphous
regions throughout the entire system
 also called mucilage
 organic gels

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SEMISOLIDS - Terminologies
Hydrogels • Gels containing water

Organogels • Gels containing organic liquid

Highly hydrated
• Diffusion occurs through pores
gels

• Drug dissolves in the polymer and

Lower hydrated gel transported between chains

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SEMISOLIDS
B. Gelatins
 Most widely employed natural polymer in
pharmaceutical products
 Used in the preparation of:
 Soft and hard gelatin capsules
 Tablet granulation
 Coatings
 Emulsions
 Suppositories

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SEMISOLIDS - Classification
 Organogels
 Gels that contain organic liquid
 Ex. Petrolatum
 Consist of
 Liquid component together with a protosubstance –
stabilized the system and thickens the gel
 Crystalline waxy fractions
 Provides rigidity to gel structure

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SEMISOLIDS- Classification
 Hydrogels
 Gels whose bases includes organic and inorganic ingredient
that are colloidally dispersible or soluble in water
 Organic hydrogels
Ex: Tragacanth, Pectin, Sodium algirate, Methylcellulose,
Sodium carboxymethylcellulose
 Inorganic hydrogels
Ex: Bentonite, mucilage

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SEMISOLIDS- Classification
 Emulsion Type Bases
 much greater affinity for water than oleaginous products
 compatible with most drugs
 w/o preparation are superior and that they do not lose water
readily by evaporation
 stable over long periods

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SEMISOLIDS- Classification
 Emulsion Type Bases
 Advantages of o/w to w/o
 easily removed from skin
 do not stain clothing
 water washable
 Disadvantage
 water loss by evaporation
 mold and bacterial growth

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SEMISOLIDS- Classification
 2 classes of Emulsion Type Bases
initially do not contain water but are capable of taking it
Emulsifiable up to yield o/w and w/o emulsion (absorption bases)

bases

• w/o bases in which water in incorporated

Emulsified • Emulsified o/w bases – any emulsion with an
aqueous phase, oil phase and emulsifying agent
bases

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SEMISOLIDS
 Instability and conditions (GELS)
• contraction of gels on standing and solvent are
squeezed out
Syneresis • presents a problem in the long term stability of
gels
• liberation of oil or water from ointment bases
Bleeding • usually results from deficient gel structure

• opposite of syneresis
Swelling • taking up of liquid with increase in volume

Thermal • increase in temp, which may cause rigid gels to

gelation melt

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