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Pestic. Sci. 1989, 25, 25-34

The Physical Stability of Suspension Concentrates with

Particular Reference to Pharmaceutical and Pesticide

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Formulations*

Paul F. Luckham
Department of Chemical Engineering & Chemical Technology, Imperial College of
Science & Technology, Prince Consort Road, London SW7 2BY, UK

(Revised manuscript received 6 January 1988; accepted 18 April 1988)

ABSTRACT

The word stability is ubiquitous in colloid science but means different things

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to dgferent people. In a suspension concentrate it is possible to identify three
different physical processes which may lead to instability in a particulate
system, namely a change in particle size due to Ostwald ripening, particle
aggregation and particle sedimentation. Although these processes may occur
simultaneously they are here treated separately in order to promote
understanding of the physical forces involved.

1 INTRODUCTION

The formulation of a pesticide or a pharmaceutical product as a concentrated

suspension may often have a considerable advantage over supplying the product
as a powder, which may be difficult to disperse. The suspension concentrate
formulation usually consists of particles covering a wide size range (0.1pm-10 pm)
dispersed in a liquid medium, generally water, at high solid volume fractions (up
to 60%). The stability of this formulation has to be controlled to satisfy various
criteria essential for the application and shelf life of the formulation, as well as its
biological or medical effectiveness. The word ‘stability’, though, is ubiquitous in
colloid science and, unfortunately, means different things to different people. First,
there are several physical processes which occur in a formulation and the stability
of the system may be discussed with respect to any of these; there is an additional
complication in that it is necessary to distinguish between ‘kinetically’ stable and
*Presented at the symposium ‘Formulation of pesticides and pharmaceuticals I--colloidal aspects’ on

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3 November 1987, organised in London by the Colloid and Surface Chemistry Group and the
Physicochemical and Biophysical Panel of the Pesticide Group, Society of Chemical Industry.
25

Pestic. Sci. 0031-613X/88/$03.50 0 1989 Society of Chemical Industry. Printed in Great Britain
26 zy
zyxwvutsrqp Paul F . Luckham

truly thermodynamically stable systems. Thermodynamic stability implies that the

system has reached its lowest free energy state so that its properties do not change
with time, whilst kinetic stability implies that the system does not change within
a certain time period although it would eventually.
At least three different physical processes may lead to instability in a particulate
system, viz.:
1. a change in the particle size distribution as a result of Ostwald ripening;
2 . aggregation of suspensions as a result of attractive inter-particle forces; and
3. sedimentation of the suspension under a gravitational field. (This may also
alter the particle size distribution throughout the formulation as large
particles settle more quickly through the suspension.)
These processes, of course, occur simultaneously. However, in order to
understand more clearly the physical forces involved in such a formulation, each
case will be treated separately, and this will promote understanding of how the
‘stability’ of suspensions may be controlled.

2 OSTWALD RIPENING (CRYSTAL GROWTH)

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Small particles are more soluble than large particles as they have a higher surface

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energy per unit mass. This may be represented by the Kelvin equation:

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where S, and S2 are the solubilities of crystals of radius rl and r, respectively, y
is the solid/solution interfacial tension, p is the density, M is the molecular weight
of the solute molecules, R is the gas constant and T the absolute temperature.
Thus, as the solvent becomes saturated with solute, the larger crystals grow
and become even larger. Another mechanism for crystal growth is related to
polymorphic changes in solutions and again the driving force is the difference in
solubility between the two polymorphs, i.e. the less soluble polymorph grows at
the expense of the more soluble polymorph.
Crystal growth may result in undesirable changes in suspension concentrates.
Increase in particle size may accelerate settling of particles leading to their caking
in the sediment (Section 4). In pesticide formulations, increase in particle size may
cause blockage of nozzles of spraying equipment and can often affect biological
efficacy. With pharmaceutical formulations, increase in particle size may affect
syringeability and cause patient discomfort. Thus control of crystal growth in
particulate dispersions is very important and remains a challenge to the formulator.
Dispersing agents (surfactants) are added to most suspensions and their role in
modifying the rate of crystal growth is crucially important. The dispersant may
affect the rate of dissolution by altering transport away from the boundary layer;
an increased rate of dissolution would thus increase the rate of crystal growth.
Dispersants may also dissolve the solute, reducing its diffusion coefficient and thus
slowing crystal growth, as well as modifying the rate of nucleation of solute on a
The physical stability of suspension concentrates 21 zy
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larger particle. Adsorption of a dispersing agent onto the surface of a crystal can
drastically change the surface energy, effectively making the surface inaccessible
to the solute and, if the dispersant is strongly adsorbed on the particle surface,
crystal growth may no longer be possible. Thus a dispersant, if properly chosen,
may be used to inhibit crystal growth in suspension concentrates. (For a fuller
discussion of this topic the reader is referred to a recent review by Tadros.’)

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3 STABILITY OF PARTICLES AGAINST AGGREGATION

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The assumption that the stability/instability of a suspension with respect to
aggregation can be described in terms of the pairwise interactions between particles
is the central premise of the classical DLVO (Derjaguin, Landau, Verwey &
Overbeek) theory of colloid stability.293Although this assumption is valid at low
volume fractions (4) of particles, it is questionable at high 4, where multiple
interactions may be important. Nevertheless, pairwise additivity is a useful
approximation to make and deviations from it do not qualitatively alter the
arguments outlined below.
In order to estimate the total free energy between two particles as a function
of their distance of separation, d, it is necessary to know the various contributions
to inter-particle forces.
3.1 Van der Waals forces
Dispersion forces between atoms arise due to fluctuating dipole-induced dipole

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interactions and the force is a l/d6 where d is the distance between the atoms.
For spherical particles of radius r , the most widely used and simplest approximation
for the free energy of interaction GA is
r(A;)- ~ j ) ,
G, =
12d2
where A , and A , are the so-called Hamaker constants of the particle and solution
respectively and are properties of the material; d is now the separation between
the particles and r the particle radius.
3.2 Electrical interactions
Particles may become charged by a variety of means, for example, isomorphic
substitution of ions (clays), protonation of acid/base groups on the surface,
adsorption of potentialdetermining ions, of ionic surfactants or of polyelectrolyte.
When a surface becomes charged, there will be an excess concentration of co-ions
close to that surface which will exactly counterbalance the surface charge. Some
of these ions will be adsorbed on the surface itself in the so-called ‘Stern plane’
(Fig. 1). The rest of the ions will, for entropic reasons, not be adsorbed exactly
at the Stern plane but will be in a diffuse layer close to the surface. The effective
thickness of this electrical double-layer is generally assumed to be K - ’ where K is
the Debye-Huckel parameter and is a property only of the liquid surrounding
28 zyxwvutsrqpo Paul F . Luckham

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the surface. For 1 :1 electrolytes zyxwvu

Fig. 1. Schematic representation of the electrical
double layer.

K is given by
St'ern
plane

where C , is the bulk electrolyte concentration, e the electronic charge, the relative
(3)

dielectric constant of the medium and E~ the permittivity of free space and T the
absolute temperature. For aqueous solutions at room temperature, values for the
thickness of the electrical double layer of approximately 100 nm, 10 nm and 1 nm
for electrolyte concentrations of and lo-' mol d m - 3 may be estimated
from eqn (3). Thus, when two charged particles approach such that their double
layers overlap, they experience a repulsion due to an increase in osmotic pressure
of the solution between the particles. Various analytical approximations have been

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derived for this electrostatic repulsion free energy, G,, and exact numerical
calculations have also been performed recently. The following equation applies
within the limits of large particles at high electrolyte solutions (i.e. Icy>> 1) and
low Stern (surface) potentials, Yd (- < 25 mV).
G, = 27m,,rY j In( 1 + exp(rcd)) (4)
Generally the experimentally measurable zeta potential is substituted for the Stern
potential.
Thus, from the above equations, it is clear that G , depends on the surface
potential Yd, particle radius r , and the salt concentration (via K ) .
For charged stabilised particles, the total interaction free energy, G,, is the sum
of the van der Waals and electrical double layer repulsive terms, i.e.
G, = G, + G, (5)
The general form of GT can easily be deduced from the way in which both
repulsion and attraction vary with the distance of separation d . The repulsion
decays exponentially with decreasing surface separation with a practical range of
the order of the thickness of the double layer. The attraction, however, decreases
as an inverse power of the distance. For very small distances, G , is very large,
consequently attraction will predominate at very small and very large distances.
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The physical stability of suspension concentrates 29

-5 0

0 25
d Inm)
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Fig. 2. The functional form of GT for an aqueous
suspension of charged spheres; Case 1 at low
electrolyte concentrations and Case 2 at high
electrolyte concentrations.

At intermediate distances, repulsion predominates as long as the electrolyte

concentration is not too high. At high electrolyte concentrations the van der Waals
term dominates and a monotonic decrease of energy with decreasing distance is
observed. These two cases are illustrated in Fig. 2 in which the curves reveal three

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important consequences:
(i) For the case of low electrolyte concentrations (case 1; Fig. 2) there is a
potential energy barrier which must be surmounted before the particles
make lasting contact in the primary minimum; if the height of the barrier
is +>lcT(the thermal energy of the particles) no such contacts will occur
and the suspension is ‘kinetically’ stable.
(ii) Since G, decays more rapidly at larger distances than G,, a secondary
minimum Gminappears in G,; if the depth of this minimum is of the order
of K T the suspension will reversibly aggregate (flocculate). G, and G, are
both proportional to the particle radius Y so that increase in particle size
makes a secondary minimum type flocculation more significant. The effect
is also more important at high electrolyte concentrations.
(iii) If G, > G, at all particle separations, irreversible aggregation (coagulation)
occurs. This is the case at low surface potentials and high electrolyte
concentrations (case 2; Fig. 2). By controlling the size, shape and charge
on the particles, the strength and nature of particle interactions may also
be controlled (Section 4).
3.3 Steric interactions
So far, only charge-stabilised systems have been considered. In many practical
cases this is not a useful form of stabilisation, for example in non-polar media,
where Yd.vO mV, and in systems where moderate electrolyte concentrations have
to be tolerated. Also, there can be problems in preparing dispersions at high solid
30

concentrations due to coagulation into a primary minimum as the particles are

packed close together. Moreover, if one wishes to weakly flocculate the system
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Paul F . Luckham

(which will prevent rapid settling of particles and leave an open flocculated structure
(Section 4)), then the depth of G,,, is difficult to manipulate in charge-stabilised
dispersions. These problems may be overcome by using polymers adsorbed to

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particles. The adsorbed polymer layer completely surrounds the particles as
illustrated schematically in Fig. 3. The van der Waals term, G,, is now characterised

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by three Hamaker constants (an additional one being due to the polymer layer);
in many cases, however, eqn (1) is still adequate, although more complicated
expressions have been d e ~ e l o p e d .The
~ total energy of interaction, G,, can be
expressed, in a similar way to eqn ( 5 ) , as the sum of G,, the van der Waals energy,
and G,, the free energy arising from the steric interaction of the polymer layers
surrounding the separate particles. As with electrostatic stabilisation, an energy
minimum can arise (Fig. 4) in which weak flocculation can occur.
When the surface separation is less than twice the adsorbed layer thickness,
the steric interaction comes into play. The precise form of the steric interaction

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has been measured experimentally’ and reasonably approximate theories
de~eloped.~.’ Conceptually, however, it is useful to consider the steric interaction
to be due to two components, one accounting for the free energy of mixing of the
polymer layers as they overlap, and a second term representing a loss in
configurational entropy of the adsorbed polymer as the particles approach. Using
this approach Napper’ has devised the following equation for the free energy of

\ ’\

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,’G*
d

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Fig. 3. Schematic representation of a polymer Fig. 4. The functional form of the interaction
coated particle. between polymer stabilised particles.
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CS = - zy
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The physical stability of suspension concentrates

interaction Gs between two particles bearing adsorbed polymer

27crkTVi n 2 r 2
(t - x)Smix+ Z n r k T T S , ,
31

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v,
where the first term is due to the free energy of mixing and the second term is due
to entropic effects. Vs and V, are the volume of a segment of polymer and a solvent
molecule respectively, n is the number of segments per polymer chain, is the
number of polymer chains per unit area and x is the Flory-Huggins’ interaction
parameter. Smixand S,, are geometric terms and are dependent on the assumed
segment density distribution of the adsorbed polymer normal to the particle
surface.

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For particles to be stable, i.e. not to aggregate, the initial stages of the interaction
between particles must be repulsive. This stage is dominated by the osmotic term.
The strength and range of this term are determined by two factors, (i) the thickness
of the adsorbed polymer layer, and (ii) the x parameter.
The adsorbed layer thickness, 8,is important, as it must be large enough lo
prevent particles aggregating due to van der Waals forces; some 5 nm or so is
typical. The x parameter is also crucially important since, if x > 0 5 , i.e. the solubility
of the polymer is poor, then the osmotic component to the steric interaction is
negative, implying that particles bearing an adsorbed layer of this polymer will

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aggregate together. There are usually clearly-defined critical conditions,
particularly of temperature, under which sterically-stabilised suspensions will tend
to flocculate, and these are often strongly correlated with the corresponding phase

TABLE 1
Comparison of Critical Flocculation Temperature (CFT) with @-Temperaturefor some

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Aqueous Dispersions (Extracted from Ref. 8)

Stabilising polymer Molecular Dispersion CFT ( K )

weight medium

Poly(oxyethy1ene) 1400 0.39 M MgSO, 317+2 330 & 10

4 700 320 327 & 5
10 000 318 319 f 3
13 500 318 315 f 3
23 000 3 14 315 f 3
Poly(acry1ic acid) 9 800 287 f2 287 f 5

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19 300 298 298 f 5
51 900 283 287 f 5
89 700 281 287 f 5
Poly(acry1ic acid) 16 000 0.2 M HC1 286 2 287 f 5
Poly(viny1 alcohol) 26 000 2.0 M NaCl 320 C 3 300k5
57 000 301 300f3
270 OOO 312 300f3
Poly(acry1amide) 18 000 2.1 M (NH&SO, 292 3 -
60 000 295 f 5 -
180 000 280 f 7 -
32 zyxwvutsrqpo
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zyx Paul F. Luckham

separation, 8, point for the polymer in solution (see Table 1 for typical examples
from the literature).
The design of steric stabilisers has been discussed elsewhere.’ Essentially the
polymer must adsorb strongly to the surface and extend sufficiently from the
particle surface to prevent aggregation by van der Waals forces. These conditions
are mutually exclusive for homopolymers but block and graft copolymers, where
one part of the polymer adsorbs strongly whilst a second part extends from the
particle surface, are particularly effective stabilisers.
It is relatively easy to modify particle-particle interactions for steric-stabilised
systems. For example, changing the molecular weight of the adsorbed polymer
changes the adsorbed layer thickness which, in turn, modifies the particle separation
where the adsorbed polymer layers initially overlap, and this determines the
strength of the van der Waals force experienced. Also by changing the solubility
conditions for the adsorbed polymer, i.e. by the addition of a non-solvent or
electrolyte, the strength and nature of the steric interaction may be modified. Thus,
control of the state of aggregation may be achieved readily for steric-stabilised
systems.

4 SEDIMENTATION

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So far, the role of external fields on the stability of suspension concentrations has
been neglected. By far the most important are gravitational or centrifugal fields,
but magnetic and electrical may be of importance in some applications and may
be treated in a similar manner to the procedure outlined below for gravitational
fields.

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The sedimentation velocity, V, of a dilute suspension of spherical, non-interacting
particles can be adequately described by the Stokes equation

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where p is the density of the particles, po is the density of the medium, g the
acceleration due to gravity and q the viscosity. This equation predicts a settling
rate of 4.4 x lO-’cm s - l for 0.1 pm particles but 4.4 x

effect of particle size on sedimentation.

cm s - l for 10pm
particles, assuming a density difference of 0.2 g cm- 3 , which illustrates the drastic

The settling of more concentrated systems is more complicated as the particles

no longer settle independently of each other. This is a result of the particles being
closer together, so that the colloidal forces outlined above become important and
retard the sedimentation rate. Various attempts have been made to modify Stokes’
equation for the rate of settling of concentrated dispersions. These efforts are
largely empirical and have been reviewed by Tadros.’
For stable suspension concentrates, however, the important target is to limit
the rate of settling. A simple method, as is evident from eqn (7), is to balance the
densities of the particles and liquid but this will only work where the density
difference is fairly small, and will not work for mixed suspensions. It should be
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The physical stability of suspension concentrates

remembered that close density-matching can only be achieved at one temperature.

It is clear from eqn (7) that an increase in the viscosity of the medium reduces
33

settling. Thus polymers and naturally-occurring gums are used as thickening

agents. In general, the higher the molecular weight of the polymer of one type
(e.g. hydroxyethylcellulose-based polymers) the lower the quantity required to
increase the viscosity. It must be recalled, however, that polymers also affect the
dispersion stability which may also alter the settling rate. The use of thickeners
does suffer from two drawbacks: (i) with pesticides, spontaneity of dispersion on
dilution is required, which is difficult to achieve with a viscous concentrate, and
(ii) the viscosity is temperature dependent and thus polymer thickeners may not
be suitable where a wide temperature range is likely to be experienced on storage.
It has long been known that fine inorganic materials such as clays and oxides,
when added to a dispersion medium of a coarser suspension, can eliminate claying.

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This is due to the fine particles forming a three-dimensional gel network in the
liquid medium, effectively increasing the viscosity of the dispersion medium and

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retarding the settling rate. Frequently, mixtures of clays and polymers are used
to control settling.
A neater method of controlling settling, however, is to control the extent of
aggregation of the dispersion. As was seen earlier, for a charge-stabilised dispersion,
the DLVO theory2j3 predicts the appearance of a secondary minimum at large

-
particle separations which may be quite deep when the particle radius exceeds

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1 pm, particularly with asymmetric particles. The depth of this minimum depends
on the Hamaker constant, the surface potential and electrolyte concentration.
Thus, by careful control of the parameters, it is possible to arrive at a secondary
minimum of sufficient depth for flocculation to occur. Flocculated systems settle
faster than stable systems but a cake does not form; instead, a relatively open
network is formed (see Fig. 5). The greater the strength of attraction between the

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particles the more open the network structure. However, if the attraction is weak,
low shearing of the system, or even dilution, causes the flocs to break and enables
rapid dispersion of the materials. Such a situation is of practical importance and
is the basis of the thixotropic behaviour shown by many concentrated dispersions.
On shaking the container, floc structure is readily broken down but reforms on
standing. By adjusting the solids concentration it is possible to arrange for the

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Fig. 5. Schematic representation of sedimenta-
tion of particulates having different types of
Repulsion Weak attrattion Strong attraction interaction.
34 zyxwvutsrq
zy Paul F . Luckham

volume of the container to be equivalent to the floc sediment volume, e.g. non-drip
paint. Although self-structuring suspensions are an ideal objective, their formation
is not an easy task. In practice, control of the parameters mentioned above requires
skill in the manufacture of the product.
For systems stabilised by polymers or non-ionic surfactants, the energy/distance
curve also shows a minimum, the depth of which depends on particle size, Hamaker
constant and the thickness of the adsorbed polymer layer, which may readily be
changed by varying the molecular weight of the polymer, so that if the adsorbed
polymer layer is not ‘too’ large a weakly flocculated thixotropic system will again
result.

ACKNOWLEDGEMENT

paper.

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The author would like to thank Dr M. A. Ansarifar for his critical reading of this

zyxwvut
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zyxw REFERENCES

1. Tadros, Th. F. Ado. Colloid Interface Sci., 12 (1980) 141-208.

2. Derjaguin, B. V. & Landau, J. Acta Physicochem. U R S S , 14 (1941) 633-49.
3. Verwey, E. J. W. & Overbeek, J. Th. G. Theory of the Stability of Lyophohic Colloids,
Elsevier, Amsterdam, 1948.
4. Vold, J. M . J . Colloid Sci., 16 (1961) 1-15.
5. Klein, J. & Luckham, P. F. Macromolecules, 17 (1984) 1041-9.
6. Scheutjens, J. M . H . M. & Fleir, G. J . Macromolecules, 18 (1985) 1882-905.
7. De Gennes, P. G. Adu. Colloid Interface Sci., 27 (1987) 189-210.
8. Napper, D. H . Polymeric Stabilisation of Colloidal Dispersions, Academic Press, New
York, 1984.