Rheology by Aliyi G.
Bule Hora University 1
Bule Hora University
College of Health and Medical Sciences
CHAPTER 7
Department Of Pharmacy
INTEGRATED PHYSICAL PHARMACY AND PHARMACEUTICS I
RHEOLOGY
8/3/2021
By: Aliyi Gerina [[Link]]
Outline
2
Introduction
Newtonian and Non-Newtonian systems
Thixotropy
Determination of viscosity
Different factors affecting rheological
properties
Pharmaceutical applications of rheology
Rheology by Aliyi G. Bule Hora University 8/3/2021
Objectives
3
At the end of this lesson the students should be able to:
Define rheology
Define and understand Newton's law of flow and its application
Differentiate flow properties and corresponding rheogram between
Newtonian and Non-Newtonian materials
Appreciate the fundamentals of determination of rheological properties
Recognize different factors affecting rheological properties of materials
Provide examples of fluid pharmaceutical products exhibiting various
rheological behaviors
Rheology by Aliyi G. Bule Hora University 8/3/2021
Introduction
4
o The term “rheology” from the Greek rheo (“to flow”) and
logos (“science”).
o It is defined as the science concerned with deformation of
matter under the influence of stress.
• Definition:
• the flow of fluids (liquids and gases) and
• the deformation of solids under the influence of shearing stress.
Rheology by Aliyi G. Bule Hora University 8/3/2021
Introduction…
5
The deformation of any pharmaceutical system can be
arbitrarily divided into two types:
• Elastic Deformation:
• it is a spontaneous and reversible deformation
• Plastic Deformation:
• it is a permanent and irreversible deformation
The plastic deformation: flow and exhibited by viscous bodies.
➢ Great importance in any liquid dosage forms like
suspensions, solutions,
Rheology by Aliyi G. emulsions etc
Bule Hora University 8/3/2021
Introduction…
6
Ideal solids deform elastically
▪ The energy required for the deformation
▪ is fully recovered when the stresses are removed
Ideal fluids such as liquids and gases deform irreversibly they flow
▪ The energy required for the deformation
▪ is dissipated within the fluid in the form of heat and
▪ cannot be recovered simply by removing the stresses.
Rheology by Aliyi G. Bule Hora University 8/3/2021
Recoverable versus permanent
The deformation is recoverable if the
7 Deformation is permanent if
material returns to its initial shape when the material remains deformed
the stress is removed. when the stress is removed.
While elastic deformation is recoverable, plastic
deformations are not
Rheology by Aliyi G. Bule Hora University 8/3/2021
Importance of Rheology
8
o In liquid, and semisolid DF: In preparation, development
and evaluation of suspensions, emulsions, pastes, suppositories,
tablets coating.
o The manufacturer of medicinal and cosmetic creams , pastes,
and lotions must be able to pour the products with an
acceptable
o consistency and
o smoothness for each batch.
Rheology by Aliyi G. Bule Hora University 8/3/2021
Importance of Rheology …
9
o Rheology involved in
✓ Mixing and flow of materials
✓ Packaging into containers
✓ Removal prior to use.
➢ Whether this is achieved by
▪ pouring from a bottle
▪ extrusion from a tube or
▪ passage through a syringe needle.
▪ The product rheology must be optimized:
▪ by controlling the viscosity of the product.
Rheology by Aliyi G. Bule Hora University 8/3/2021
Importance of Rheology …
10
o In acceptability to the patient, physical stability, and even
biological availability (i.e., viscosity affect the absorption rate of
drugs from GIT).
o Rheology properties of pharmaceutical systems can influence the
selection of equipment used in its manufacture
✓ Inappropriate equipment from rheological perspective may result in
an undesirable product, at least in terms its flow characteristics.
Rheology by Aliyi G. Bule Hora University 8/3/2021
Classification of rheological systems
11
o Materials are classified according to type of flow in to two
categories
✓ Newtonian systems
▪ Simple fluids which obey Newtonian law of flow
✓ Non-Nowtonian systems
▪ do not obey Newtonian law of flow
Rheology by Aliyi G. Bule Hora University 8/3/2021
Newtonian systems : Viscosity
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▪ The flow of liquids or semisolids is described by viscosity.
A fluid’s internal resistance to flow
and may be thought of as a measure
of fluid friction
Measure of the resistance of liquid
Viscosity to deformation under shear stress
The resistance offered when one part
of the liquid flows past another.
Rheology by Aliyi G. Bule Hora University 8/3/2021
Newtonian fluids: Viscosity…
13
Newtonian law of flow
o The phenomenon of viscosity is best understood by a consideration
of a hypothetical cube of fluid made up of infinitely thin layers
o which are able to slide over one another like a pack of playing cards.
o When a tangential force is applied to the uppermost layer
✓ each subsequent layer will move at progressively decreasing velocity and
the bottom layer will be stationary.
Rheology by Aliyi G. Bule Hora University 8/3/2021
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Rheology by Aliyi G. Bule Hora University 8/3/2021
Newtonian fluids: Viscosity…
15
The bottom layer is considered to be fixed in place
The adhesive force between the wall and the flowing layers
Inter-molecular cohesive forces
Inter-molecular force (viscous forces) : viscosity
Viscosity is the opposing force to flow,
◼ it is characteristic of the medium.
In other words, viscosity describes the internal friction of a moving
fluid.
Rheology by Aliyi G. Bule Hora University 8/3/2021
Newtonian fluids: Viscosity…
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o A velocity gradient will therefore exist, and
o this will be equal to the velocity (ms-1) of the upper layer in
divided by the height (m) of the cube.
o Fig. Representation of the shearing force required to produce a definite velocity
gradient between the parallel planes of a block of material.
Rheology by Aliyi G. Bule Hora University 8/3/2021
Newtonian fluids: Viscosity…
17
The difference in velocity (dv) b/n two planes
of a liquid separated by an infinitesimal
distance (dx) is the velocity gradient or a rate of shear (dv/dx
or G).
Shear rate (G) = dv/ dx
o The resultant velocity gradient is the rate of shear, G,
will have units s-1.
Rheology by Aliyi G. Bule Hora University 8/3/2021
Newtonian fluids: Viscosity…
18
The force required for one layer of a liquid to slip past
another layer with a given velocity depends
Directly
◼ on the viscosity ofthe liquid and
◼ on the areas of layers exposed to each other and
Inversely on the distance separating the two surfaces.
A fluid with high viscosity resists motion
because its molecular make up gives it a lot of internal
friction.
18
Rheology by Aliyi G. Bule Hora University 8/3/2021
Newtonian fluids: Viscosity…
19
o The applied stress,the shear stress,
o S , is derived by dividing the applied force, F’, by the area of the
upper layer.
o It have units of N m-2.
Shear stress (S) = F’/ A
Rheology by Aliyi G. Bule Hora University 8/3/2021
Newtonian fluids: Viscosity…
20
Newton recognized that: the higher the viscosity of a liquid, the greater the
force per unit area required to produce a certain rate of shear
Thus, the rate of shear is to the shearing stress
Newtonian law Absolute viscosity or dynamic viscosity
F ' dv F'
F'
=
dv
= A = =
S Shearing Stress
A dx A dx dv G Rate of Shear
dx
Where is a constant known as coefficient of viscosity, usually
referred to simply as viscosity or absolute viscosity.
Where
S is the shearing stress ([Link]-2)
G is the rate of shear (sec-1)
Units: dynes-sec/cm 2
SI unit: N-sec/m2
Rheology by Aliyi G. Bule Hora University 8/3/2021
Newtonian fluids: Kinematic Viscosity
21
It is the absolute viscosity divided by the density of liquid
at a specified temperature.
KV = η/p
The preferred unit when the shear stress and shear rate of the fluid
are influenced by the density.
Units: Stock (s) or centistokes .
Rheology by Aliyi G. Bule Hora University 8/3/2021
Newtonian fluids
22
Liquids that obey Newton’s law of flow:
Newtonian liquids
Newton’s equation for the flow of a liquid is
S=η*G
Plot of shear stress Vs shear rate:
the slope gives the viscosity.
The curve always passes through the origin.
The reciprocal of viscosity is called fluidity: 1/η = Slope
Rheology by Aliyi G. Bule Hora University 8/3/2021
Characteristics of Newtonian flow
23
o The passage through the origin indicateso The linear nature of the curve
that shows that the viscosity (η) of a
o even a mild force can induce flow in
Newtonian liquid
these systems. o is a constant unaffected by
the value of the rate of shear.
Rheology by Aliyi G. Bule Hora University 8/3/2021
Newtonian fluids…
24
o Examples of Newtonian fluids include:
▪ Water
▪ Air
▪ Glycerin and most mineral oil
▪ True solutions
▪ Very dilute suspension and emulsions
▪ Liquid paraffin
Rheology by Aliyi G. Bule Hora University 8/3/2021
Non-Newtonian systems
25
o Most pharmaceutical fluids do not follow Newtonia law
o because the viscosity of the fluid varies with the rate of shear.
o These materials are non-Newtonian fluids.
o The viscosities of non-Newtonian fluids vary with shear rate
stating a single viscosity is misleading : apparent viscosity
Rheology by Aliyi G. Bule Hora University 8/3/2021
Non-Newtonian system…
26
o It can be seen in liquid and solid heterogeneous dispersions
o such as colloids, emulsions, liquid suspensions and ointments.
o there are three classes of non-Newtonian flow
➢ plastic,
➢ pseudoplastic
➢ dilatant
Rheology by Aliyi G. Bule Hora University 8/3/2021
Plastic flow (Bingham bodies)
27
A plastic material does not flow
until a certain minimum shearing stress, the yield value, is
applied.
The substance initially behaves like an elastic body and fails
to flow when less amount of stress is applied.
Further increase in the stress leads to a nonlinear and
increase in the shear rate which then turns to linearity
Rheology by Aliyi G. Bule Hora University 8/3/2021
Plastic flow,…
28
The slope of the rheogram is termed
mobility, analogous to fluidity in
Newtonian systems and its reciprocal is
known as the Plastic viscosity, U
Where u is the plastic viscosity and
f is the Bingham yield stress or
value
Rheology by Aliyi G. Bule Hora University 8/3/2021
Plastic flow,…
29
Extrapolations of the linear plot gives
‘x’ intersect: yield value.
This curve does not pass through the
origin
Intersects the shear stress axis at a
particular point, yield value.
As the curve above yield value tends
to be straight,
the plastic flow is similar to the
Newtonian flow above yield value.
Rheology by Aliyi G. Bule Hora University 8/3/2021
Plastic flow,…
30
Flocculated particles in a concentrated suspensions usually
show plastic flow.
The yield value represents the stress required to break the inter-
particular contacts so that particles behave individually.
Thus it is indicative of the forces of flocculation
◼ increased by the increased concentration of the dispersed phase.
Rheology by Aliyi G. Bule Hora University 8/3/2021
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Rheology by Aliyi G. Bule Hora University 8/3/2021
Plastic flow,…
32
o Other examples of plastic flow:
✓ Solid powder materials
✓ Topical ointments
✓ Pastes
Rheology by Aliyi G. Bule Hora University 8/3/2021
Pseudo-plastic Flow (shear thinning)
33
Pseudo plastic flow is exhibited by polymer dispersions like:
Tragacanth in water
Sodium alginate in water
Methyl cellulose in water
Sodium carboxy methyl cellulose in water
Rheology by Aliyi G. Bule Hora University 8/3/2021
Pseudo-plastic Flow…
34
The relationship between shear The viscosity of a pseudo-plastic
stress and the shear rate substance decreases with
increasing G (shear-thinning
is not linear and the curve
systems).
starts from origin.
Rheology by Aliyi G. Bule Hora University 8/3/2021
Pseudo-plastic flow behavior; Structural reasons
35
At rest, the linear polymers dispersed at random in the
dispersion medium.
As shearing stress is applied, the macromolecules become
aligned with the long axis parallel to the direction of
flow.
With this ordered alignment the molecules pass one
another with less frictional resistance, and the viscosity
is decrease.
Rheology by Aliyi G. Bule Hora University 8/3/2021
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Rheology by Aliyi G. Bule Hora University 8/3/2021
Pseudo-plastic Flow…
37
Rheology by Aliyi G. Bule Hora University 8/3/2021
Pseudo-plastic Flow…
38
If the S is decreased, the orientation of the macromolecules
becomes more random.
Greater frictional resistance to the flow is reflected in an
increased viscosity.
Since only a molecular alignment is involved
Emulsions and dispersions of many types: shear-thinning
Rheology by Aliyi G. Bule Hora University 8/3/2021
Dilatant Flow(Shear thickening)
39
Resistance to flow (viscosity) increases with increase in shear
stress.
When S is applied their volume increases and
◼ hence they are called Dilatant.
This property is also known as shear thickening
Dilatant flow is observed in suspensions containing
more than 50%W/V of solids,
deflocculated particles .
Rheology by Aliyi G. Bule Hora University 8/3/2021
Dilatant Flow,…
40
Rheology by Aliyi G. Bule Hora University 8/3/2021
Dilatant Flow,…
41
At rest, the particles are closely packed with a
minimum interparticle volume, or voids.
The vehicle is sufficient to fill this volume.
As the shear stress is increased, the bulk of the system
expands or dilates.
Increase in the inter-particle void volume
◼ Vehicle become insufficient to fill the increased voids.
• The resistance to flow increases:
➢ This process is reversible
Rheology by Aliyi G. Bule Hora University 8/3/2021
Dilatant Flow,…
42
o The effect is reversible and removal of the shear stress results in
the re-establishment of the fluid nature.
Rheology by Aliyi G. Bule Hora University 8/3/2021
Dilatant Flow,…
43
o Dilatancy can be a problem during the processing of
dispersions and the granulation of tablet masses when
high-speed blenders and mills are employed.
▪ If the material being processed becomes dilatant in nature then
the resultant solidification could overload and damage the
motor.
Rheology by Aliyi G. Bule Hora University 8/3/2021
summary
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Rheology by Aliyi G. Bule Hora University 8/3/2021
Thixotropy
45
o Non-Newtonian,
➢ Time dependent behavior.
o Definition
o Thixotropy: It is the decrease in viscosity as a function of
time upon shearing, then recovery of original viscosity as a
function of time without shearing.
o Thixotropic material is
o any material that exhibits a reversible time-dependent decrease in
apparent viscosity.
Rheology by Aliyi G. Bule Hora University 8/3/2021
Thixotropy,...
46
Thixotropic substances on applying shear stress convert to
sol (fluid) and on standing they slowly turn to gel
(semisolid).
Rheology by Aliyi G. Bule Hora University 8/3/2021
Reason for thixotropic property
47
Thixotropic systems contain
asymmetric particles which
set up a loose three
dimensional structure which is
◼ rigid and resembles a gel which is
broken down on applying shear:
Solution
◼ On removing the applied stress,
the material reform its original
structure of state: Gel
Rheology by Aliyi G. Bule Hora University 8/3/2021
Thixotropy,...
48
o Rheogram : show a hysteresis where, as the S is
increased an up-curve is obtained, on reducing the S
gradually a down curve shifted to the left side is obtained.
o In the case of
o plastic and
o pseudoplastic materials the downcurve will be displaced to the
right of the upcurve.
Rheology by Aliyi G. Bule Hora University 8/3/2021
Thixotropy,...
49
Rheogram of thixotropic materials depends on
Applied shear rate or shearing force
The length of the time a sample is subjected to
shearing or kinematic history.
The previous history of the sample has
significant effect on
the rheologic properties of a thixotropic system.
50
Rheology by Aliyi G. Bule Hora University 8/3/2021
Thixotropy,...
50
Thixotropic substances are now a day’s more used in
suspensions to give stable suspensions.
On storage turn to gel: viscosity increases infinitely, do not allow
the dispersed particles to settle down:
◼ stable suspension
When shear stress is applied they turn to solution and
◼ thus are easy to pour and measure for dosing.
Solve the problems,
stability and
pourability.
Rheology by Aliyi G. Bule Hora University 8/3/2021
Thixotropy,...
51
Examples
Gels that show thixotropic flow
include aluminum hydroxide gel and bentonite magma
Paints are also another example of thixotropic fluids
When modern paints are applied the shear created by the brush
or roller will allow them to thin and wet out the surface evenly
Once applied the paints regain their higher viscosity which
avoids drips and runs.
Rheology by Aliyi G. Bule Hora University 8/3/2021
Irreversible Thixotropy
52
Application of shear stress causes breakdown of structure
within the system but
The structure does not reform on removal of the shear stress,
or
The time lag is so long that from a practical point of view
the effect is irreversible.
Example: gels produced from higher [Link] polysaccharides
On application of high shear,
◼ The 3D structure of the polysaccharides is reduced to a 2D
one and
▪ The original gel-like structure is never recovered.
Rheology by Aliyi G. Bule Hora University 8/3/2021
Negative thixotropic or Antithixotropy
53
Antithixotropy is believed to result from an increased collision
frequency of the dispersed particles in suspensions which
results in an increased inter-particle bonding with time.
This changes the original state of the system from a network of a
large number of individual particles and small floccules to an
equilibrium state consisting of a small number of relatively large
floccules.
Which helps the dispersed particles to acquire a random orientation
and the network is established: Gel
Rheology by Aliyi G. Bule Hora University 8/3/2021
Negative thixotropic…
Negative thixotropic or Antithixotropy…
54
At rest the large floccules break up and gradually return to the
original state of small floccules and individual particles.
viscosity decreases: Solution
Rheology by Aliyi G. Bule Hora University 8/3/2021
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Rheopexy is the conversion of solids to gel up on
application of shearing stress.
Substances with low melting point
shows rheopectic property.
Example: polymers with low melting point
Rheopectic fluids are rarely encountered
Rheology by Aliyi G. Bule Hora University 8/3/2021
Determination of the rheological properties
56
o Different equipments called viscometers are used to measure
rheological properties
o such as viscosity of different fluids and semisolids.
o Successful determination and evaluation of rheologic properties of
any particular system depend on choosing the correct instruments
▪ For Newtonian system
▪ Single point instruments can be used
➢ Instruments that operate at a single rate of shear.
▪ For no-Newtonian system,
▪ multipoint instruments should be used
➢ instruments that can operate at different rates of shear
Rheology by Aliyi G. Bule Hora University 8/3/2021
Determination of the rheological properties…
57
Ostwald Viscometer
It is a type of capillary viscometer
This is ‘U’ shape tube with two bulbs and two marks .
It is used to determine the viscosity of Newtonian
liquids.
Rheology by Aliyi G. Bule Hora University 8/3/2021
Determination of the rheological properties…
58
Principle:
When a liquid flows by gravity, the time required for the
liquid to pass between two marks, upper mark and lower
mark,through a vertical capillary tube is determined.
The time of flow of the liquid under test is compared with
the time required for a liquid of known viscosity (usually
water).
Rheology by Aliyi G. Bule Hora University 8/3/2021
Determination of the rheological properties…
59
The viscosity of unknown liquid η1 can be determined
using the equation
η1 = (ρ 1t1 ) η2
ρ 2t2
ρ1= Density of unknown liquid
ρ2= Density of known liquid
t1= Time of the unknown liquid
t2= Time of the known liquid
η 2= Viscosity of known liquid
Rheology by Aliyi G. Bule Hora University 8/3/2021
Determination of the rheological properties…
60
Falling-sphere viscometer
Consists of cylindrical transparent tube having
graduated section near the middle of its length and
generally a steel ball that is allowed to fall through the tube.
Rheology by Aliyi G. Bule Hora University 8/3/2021
Determination of the rheological properties…
61
The tube is filled with the liquid whose viscosity is to be determined
and the ball is allowed to fall.
The velocity of the falling ball is measured and viscosity is calculated
using stoke’s law
V= d2 (ρ s- ρ o ) g
18
where d= Diameter of the falling ball; ρ s =Density of the sphere;
ρ l=Density of liquid; g= Gravitational acceleration; v = Terminal settling
velocity
2
As d g/18 is constant, can be replaced by another constant ‘K'
Therefore, the equation will be
= K(ρ s- ρ 1 )
V
Rheology by Aliyi G. Bule Hora University 8/3/2021
Factors affecting rheological properties
62
Chemical factors
Extent of Polymer Hydration
In hydrophilic polymer solution the molecules are regarded
as completely surrounded by immobilized water molecules
forming a solvent layer.
Such hydration of hydrophilic polymers gives rise to an
increased viscosity.
Rheology by Aliyi G. Bule Hora University 8/3/2021
Factors affecting rheological,…
63
Impurities, Trace Ions and Electrolytes
Chemical impurities are the major factors in changing the
viscosity of natural polymers.
At high conc. =>compete for adsorbed water molecules
surrounding the hydrated polymer => the polymer
become dehydrated => the viscosity of the dispersion
decreased => precipitation occurs.
Rheology by Aliyi G. Bule Hora University 8/3/2021
Factors affecting rheological,…
64
Physical factors
Temperature
A temperature increase usually produces a rapid viscosity
decrease.
Prolonged heating may produce drastic decrease in
viscosity
◼ due to decomposition of the polymer,
e.g., gelatin.
Rheology by Aliyi G. Bule Hora University 8/3/2021
Factors affecting rheological,…
65
Concentration
In concentrated suspensions:
a decrease in particle size or an increase in the surface area of
the solid phase produce an increase in the viscosity of the
system.
This due to immobilization of the vehicle with an increase in
the fraction of the suspension volume occupied by the solid.
Rheology by Aliyi G. Bule Hora University 8/3/2021
Significance of rheology
66
Rheology of emulsion
o All except dilute medicinal emulsions exhibit
o non-Newtonian behavior.
o The fluid emulsions
o are usually pseudoplastic.
o Those approaching a semisolid nature behave
o plastically.
o The semisolid creams
o are usually viscoelastic.
Rheology by Aliyi G. Bule Hora University 8/3/2021
Significance of rheology …
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Rheology of suspension
o Most exhibit plasticity and pseudoplasticity along with
thixotropy.
o The rheological properties of suspensions are markedly
affected by
▪ the degree of flocculation
▪ The types and quantities of suspending and
▪ thickening agent.
o Preferred rheological properties
▪ Pseudoplasticity
Rheology by Aliyi G. along with
Bulethixotropy
Hora University 8/3/2021
Significance of rheology …
68
o Flocculated suspensions will exhibit
o plastic or
o pseudoplastic (more usually) behaviour.
o If the breakdown and reformation of the bonds between
floccules is time dependent then thixotropic behaviour will
also be observed.
o Concentrated deflocculated suspensions exhibit
o dilatancy.
Rheology by Aliyi G. Bule Hora University 8/3/2021
Significance of rheology …
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Rheology of semisolids
o Rheological characteristics of semisolids affect
▪ The stability and their extrudability from tubes
▪ The capacity to take up solids or liquids
▪ The spreadabilty on the skin and
▪ Release of active from the base.
Rheology by Aliyi G. Bule Hora University 8/3/2021
Significance of rheology …
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o Most of the topical semi-solids
o show plastic flow behaviour.
o Hydrocarbon bases (e.g petrolatum) exhibit
o plastic flow with varying degree of thixotropy..
o Some paste exhibit
o dilatancy when subject to shear where as others demonstrate typical
o pseudoplastic flow with thixotropy
Rheology by Aliyi G. Bule Hora University 8/3/2021
Significance of rheology …
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Rheology of powders
o Good flow property of powder are required to ensure
uninterrupted flow from hopper and into the die cavities
▪ in high speed tabletting machines
▪ during encapsulation and
▪ during the packaging
o Factors affecting the flow properties of particulate solid are
▪ the surface characteristics and
▪ Stickiness.
Rheology by Aliyi G. Bule Hora University 8/3/2021
Significance of rheology …
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o Improvement in the flow characteristics can be achieved by
▪ reducing the surface roughness of particle
✓ reduced by the presence of fines in powder
✓ which fill the irregularities.
▪ reducing the stickiness b/n particles
✓ reduced by the addition of lubricant
✓ such as talc, starch and magnesium strearate
Rheology by Aliyi G. Bule Hora University 8/3/2021
Significance of rheology …
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Rheology and processing
o The rheological considerations of the material are important
o to ensure proper mixing.
o Large impellar operating at a low shear rate is required
o for shear thinning systems.
o Semisolid material exhibiting dilatant properties
o should be processed with low shear mixer.
Rheology by Aliyi G. Bule Hora University 8/3/2021
Significance of rheology …
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o Low shear mixing is sometimes required in certain
polmeric dispersion
o in order to prevent the breakdown of struture due to
depolymerisation at high shear rates.
o Rheological considerations are also important
o during fluid transfer including pumping from one vessel to
another and flow though pipes.
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Thank You!!!
Rheology by Aliyi G. Bule Hora University 8/3/2021
