Suspensions are finely divided drugs dispersed in a liquid vehicle. They can be stabilized through electrostatic, steric, or hydration repulsive forces between particles. Emulsions are dispersions of one liquid in another, stabilized by surfactants. Key parameters that impact stability include choice of emulsifier, phase ratio, manufacturing method, and temperature during processing and storage. Different types of suspensions and emulsions exist for various dosage forms. Understanding colloid science principles is important for developing stable formulations.

1. A Formulators Guide - Jim McElroy

2. ◦ Suspensions are classified on the basis of the
Dispersed Phase (DP) and the Dispersion Medium
(DM).
◦ The former (DP) is essentially a solid while the latter
(DM) may either be a solid, a liquid or a gas.

3. ◦ USP defines suspensions as “finely divided,
undissolved drugs dispersed in liquid vehicles.”
◦ The USP defines several suspension dosage forms
that are historically referred to by other names.
They are:
 Milks (flocculated suspensions)
 Gels *(structured vehicle)
 Lotions and Creams (emuslions)
 *If the DP is soluble in the DM then this gel is not a
suspension.

4. • Electrostatic Repulsive Force
• Steric Repulsive Force
• Van de Waals Force
• Repulsive Hydration force

5. ◦ Electrostatic Repulsive Force – charged particles
exert a force on one another.
 e.g. Ionic molecules keep the particles apart
◦ Steric Repulsive Force – arises from the adsorption
of large molecules. Can be controlled by
formulation
 e.g. Sterically stabilized dispersions are stable when
the polymer is soluble.

6. -
-
- -
-
-
- -
+
+
+
+
+
+
++
+
+
Electrostatically Stabilized Sterically Stabilized

7. ◦ Van de Waals Force - attractions between atoms,
molecules, and surfaces.
 e.g. particles overcome the repulsion forces (possibly
due to Brownian motion or differential sedimentation
rates, agglomerate and attract each other
◦ Repulsive Hydration Force – arises from the
structuring of water in the interfacial region.
Operates over short distances.
 e.g. it is controlled by the interdependcence of ionic
strength, surface charge density, particle size and
surface dipole density

8.  Colloid science has held that electrostatic and
electrodynamic (van der waals) forces are
principle determinants of colloid systems.
 Interaction between two dipoles that are
either permanent or induced. The temporary
dipole and the induced dipoles are attracted
to each other. It is always present, it is short-
range, and it is attractive.

9.  Hydration Repulsion is:
◦ work needed to remove water molecules from
hydrophilic(water loving) surfaces at small film
thicknesses and is described by an exponentially
decaying interaction potential.

10. Charge at
the true
surface
adsorbed counterions tightly
bound and move with the
solid
complete
neutralization
of the surface
charge
complete
neutralization
of the Nernst
potential
thickness of the double layer is
inversely related to ionic strength
and ion valence

11. • Flocculated Suspension
• Structured Vehicle
• Emulsions

12. ◦ Particles finer than 0.1 µm in water remain
continuously in motion due to
electrostatic charge (often negative) which
causes them to repel each other.
◦ The distance between particles is
approximately 100 to 200 A.
◦ The network is easily disrupted by shaking
but it reforms when the turbulence stops.

13.  Rapid rate of sedimentation due to large size
of floccules
 Clear supernatant as all particles are
incorporated into floccules
 High sediment volume
 Sediment easily re-dispersed by shaking

15. ◦ Adjust electrostatic repulsive force
 use an electrolyte
◦ Modify the Nernst (equilibrium) potential
 reduce surface charge by adsorbing
anions to it
◦ Adjust steric repulsive force
 adsorb a neutral polymer
◦ Heteroflocculation
 Add small oppositely charged particles to
produce a particle network

16.  Adjust or modify:
 the Nernst Potential using an ionic species
such as phosphate anions
 the electrostatic repulsive force by using an
electrolyte like sodium chloride
 The steric repulsive force adsorbing a neutral
polymer like polyvinyl alcohol

17. ◦ Produce a liquid phase which exhibits
shear thinning rheology, i.e. very viscous
on the shelf to prevent settling and fluid
when shaken.
◦ Usually contains a polymer and a clay (or
several polymers) in order to produce a
shear-thinning system.

18. ◦ May appear as a semi-solid when
undisturbed
◦ Fluid when shaken
◦ Thixatropic (becomes fluid when stirred or
shaken and returning to the semisolid
state upon standing )
◦ No sedimentation

19.  Exhibited by polymer solutions. Increasing
flow as the shear stress is increased. The
viscosity decreases as the shear stress is
increased.

20.  The system becomes
more viscous as the
shear stress is
increased.
 Note: Production equipment
often introduce more shear
than laboratory equipment.

21. ◦ Addition of “inert” small particles such as
clays like montmorillonite or silica dioxide
◦ Mixture of polymers and “inert” small
particles like sodium
carboxymethycellulose with
montmorillonite or silica dioxide
◦ Use of liquid-crystalline phases with
surfactants at concentrations above the
Critical Micelle Concentration (CMC).

22.  A two phase system consisting of two
incompletely immiscible liquids, one of
which is dispersed as finite globules in the
other.
 The particle size of the globules range from
0.1 to 10 microns.
 A surfactant system and (usually)
mechanical energy are needed to join the
phases.

23.  All emulsions eventually coalesce to reduce
the total free energy of the system…
the emulsion “breaks”

24. • Oil-in Water
• Water-in-Oil

26.  Important parameters include:
◦ Choice of emulsifiers
◦ Phase-Volume Ratio
◦ Method of Manufacture
◦ Temperature (processing and storage)
The better the emulsifying system the less
important the other factors

27.  Anionic - hydrophilic group has an anionic charge e.g. soaps,
shampoo, detergents
 Cationic - have a cationic charge e.g. preservatives,
conditioners
 Nonionic - no charge e.g. food additives
 Amphoteric - contains two oppositely charged groups e.g.
lysergic acid, psilocybin
 Finely Divided Solids – e.g. clays, bentonite (called a Pickering
Emulsion)
 Proteins - e.g. casein, egg yolks
 Naturally Occurring – e.g. lanolin, lecithin, acacia, carrageen
and alginates

28.  Molecules at an interface will align in the easiest
transition between two bulk phases.
 In a solution of water , surfactant molecules align
so that its polar groups are immersed in water
and its chains are sticking out into the air phase
 In an oil/water dispersion, surfactant molecules
align so that its polar groups are immersed in
water and its chains are sticking out into the oil
phase

29.  Emulsions change their size distributions over time
with the average droplet size shifting to larger
values
 A sharply defined distribution containing a the
maximum fraction of small-diameter droplets is
usually more stable

30.  Continuous Phase: O/W emulsion can be partially
controlled by clays and gums W/O emulsion by the
addition of high-melting waxes and polyvalent
metal soaps
 Internal Phase: No impact to final emulsion
viscosity
 Droplet Size & Distribution: The viscosity of
emulsions having similar size distributions about a
mean diameter is inversely proportional to the
mean diameter

31.  Method of Preparation
◦ Order of addition
◦ Rate of addition
◦ Energy effects

32. Placement of surfactants:
 Ideally, lipophilic surfactant should be dispersed in
the oil phase. Finer emulsions result when the
hydrophilic surfactant is also dispersed in the oil
phase.
Oil to water or water to oil:
 If processing permits, addition of aqueous to the
oil phase produces the finest emulsions.
 If the oil phase is added to the aqueous phase,
more energy will be required to produce small
droplets.

33.  A significant improvement in the emulsion can
sometimes be seen by adding the aqueous phase at
a slower rate.

34.  Emulsions can be sensitive to energy input
or energy removal from the system
 Cooling rate can impact the system
 Mechanical or heat energy will not
overcome systemic problems with a
formula

35.  Temperature can affect:
◦ The rheology of the system
◦ The HLB of the emulsifiers
◦ The ability of the emulsifier to adsorb or
desorb from the droplet interface
◦ The mechanical strength and the elasticity
of the interfacial film.

36.  It is an emulsion that is stabilized by solid particles
(for example colloidal silica) which adsorb onto the
interface between the two phases.
 Generally the phase that preferentially wets the
particle will be the continuous phase in the
emulsion system.
 Sunscreens fall typically into this category

37.  Oil, water and surfactants
 High concentration of surfactant relative to
the oil (~50%)
 System is optically clear fluid or gel
 Phases do not separate on centrifugation
 System forms spontaneously

38.  Suspensions are a preferred and widely
accepted pharmaceutical dosage form.
 Creating a stable formula that is efficacious
requires some knowledge about the basic
physics of the suspension/emulsion to be
deployed
 Ingredients are key