Physical

Pharmaceutics II –
BP403T
Dr. Asim Kumar Samanta
Assistant Professor
Dr. Vishwanath Karad MIT World Peace University,
School of Health Science and Technology,
Kothrud, Pune, Maharashtra 411038
Rheology
Unit II

2
Syllabus
• Rheology:
• Newtonian systems, law of flow, kinematic viscosity, effect of temperature,
• Non-Newtonian systems, pseudoplastic, dilatant, plastic, thixotropy,
thixotropy in formulation,
• Determination of viscosity, capillary, falling Sphere, rotational viscometers
• Deformation of solids:
• Plastic and elastic deformation, Heckel equation, Stress, Strain, Elastic
Modulus

3
Rheology
• Rheology word derived from Greek rheos meaning ‘flow’ and logos
meaning ‘science’
• Rheology is the study of the flow or deformation of matter under the
influence of stress.
• Study of flow properties of liquids is important for pharmacist working in
the manufacture of several dosage. forms, viz., simple liquids, gels,
ointments, creams, and pastes.
• These systems change their flow behavior when exposed to different stress
conditions.
• Manufacturers in cosmetic and medicinal industries rely on rheology to
ensure consistent product quality.
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Importance and Fundamentals
• Formulation of medicinal and cosmetic creams, pastes and lotions.
• Formulation of emulsions, suspensions, suppositories, and tablet
coating.
• Fluidity of solutions for injection.
• In mixing and flow of materials, their packaging into the containers,
their removal prior to use, the pouring from the bottle.
• Extrusion of a paste from a tube
• Passage of the liquid to a syringe needle.

5
Importance and Fundamentals
• Impact on Patient Acceptability:
• Rheology of a particular product can affect its patient acceptability, physical
stability, and even biologic availability. For example, viscosity has been shown
to affect absorption rates of drugs from the gastrointestinal tract.
• Equipment Selection in Manufacturing:
• Rheological properties play a role in the selection of processing equipment for
pharmaceutical systems. Inappropriate equipment may lead to undesirable
flow characteristics and impact the quality of the final product.

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Newton's Law of Flow
• According to Newton’s law, higher the viscosity of a
liquid, the greater is the force per unit area
(shearing stress F) required to produce a certain
rate of shear (G).
• Velocity gradient or rate of shear (G) should be
directly proportional to shearing stress (F)

Taking the proportionality constant as η

or,

Where, F = F’/A
G = dv/dr
η = coefficient of viscosity, usually referred to simply as
viscosity 7
Newtonian fluids
• Newtonian fluids: Fluids that obey Newton’s law of flow
i.e. fluid whose stress versus rate of shear curve is linear
and passes through the origin, are called Newtonian fluids.

or,
• Flow curve or Rheogram obtained by plotting F versus G
for a Newtonian system where a straight line passing
through the origin.
• Viscosity (η): It is the property of the body to resist the
flow.
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Viscosity
• Viscosity (η): It is the property of the body to resist the flow.
Viscosity is the internal friction in the fluid, i.e. resistance to the
relative motion of the adjacent layers of a liquid.
• Unit of viscosity: Poise
• Poise: Shearing force (F) required to produce a velocity of 1
cm/sec between two parallel planes of liquid each 1 cm2 in area
and separated by a distance of 1 cm.
• CGS units for poise are dyne sec/cm2 or g/cm sec.
• A more convenient unit for most work is the centipoise (cp, plural
cps). 1 cp = 0.01 poise.
• Fluidity (φ) a term sometimes used, is defined as the reciprocal of
viscosity
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Absolute Viscosity of Some
Newtonian Liquids at 20°C

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Kinematic viscosity
• Kinematic viscosity is the absolute viscosity divided by the density of
the liquid at a specific temperature:

• Units of kinematic viscosity are the stoke (s) and the centistoke(cs).
• An Ostwald viscometer was used to measure acetone, which was
found to have a viscosity of 0.313 cp at 25°C. Its density at 25°C is
0.788 g/cm3. What is the kinematic viscosity of acetone at 25°C?
• Water is ordinarily used as a standard for viscosity of liquids. Its
viscosity at 25°C is 0.8904 cp. What is the viscosity of acetone relative
to that of water (relative viscosity, ηrel) at 25°C?
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Effect of temperature
• The dependence of the viscosity of a liquid on temperature is
expressed approximately for many substances by an equation
analogous to the Arrhenius equation of chemical kinetics

Where, A = constant depending on the molecular weight and molar volume of the liquid
Ev = activation energy required to initiate flow between molecules

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Non-Newtonian flow
• Non-Newtonian fluids are fluids with no direct linear relationship
between shear stress and shear rate, i.e. they do not follow Newton’s law
of flow.
• Majority of fluid pharmaceutical products are not simple liquids and do
not follow Newton's law of flow.
• Non-Newtonian behavior is generally exhibited by liquid and solid
heterogeneous dispersions such as colloidal solutions, emulsions, liquid
suspensions, and ointments.
• Three classes
• Plastic flow
• Pseudoplastic flow
• Dilatant flow 13
Plastic flow
• Plastic flow curve intersect the axis of shear stress at some point without
passing through origin.
• If straight part of the curve extrapolated to the axis it is called yield point
or yield value.
• Materials does not begin to flow until a shearing stress corresponding to
the yield value is exceeded.
• At stresses below the yield value, the substance acts as an elastic
material.
• The equation describing plastic flow is

• The slope of the rheogram in is termed the mobility, analogous to

fluidity in Newtonian systems, and its reciprocal is known as the plastic
viscosity (U) and f is the yield value, or intercept, on the shear stress axis
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in dynes/cm2
Plastic flow
• So plastic flow shows Newtonian flow above yield value.
• Yield value is important for certain dispersions.
• Materials which show this type of behavior are termed as
Bingham bodies.
• Concentrated flocculated suspensions (e.g. concentrated zinc
oxide suspension) and semisolid dosage forms, such as gels,
creams and ointments, are examples of plastic materials.
• Association with Concentrated Suspensions:
• Plastic flow is linked to the presence of flocculated particles in
concentrated suspensions. The continuous structure formed by these
particles creates a yield value, which represents the force of
flocculation. Frictional forces between particles can also contribute to
the yield value.
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Pseudoplastic flow
• In pseudoplastic flow, curve is passing from origin
(Zero shear stress), so no yield value is obtained. As
shear stress increases, shear rate increases but not
linear  Viscosity of a pseudoplastic substance
decreases with increasing rate of shear and called
shear thinning system
• Because no part of the curve is linear the viscosity
of a pseudoplastic material cannot be expressed by
any single value an apparent viscosity can be
determined at any shear rate from the slope of the
tangent to the curve.
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Pseudoplastic flow
• Many pharmaceutical products, including
liquid dispersions of natural and synthetic
gums exhibit pseudoplastic flow
• Example: tragacanth, sodium alginate,
methylcellulose, and sodium carboxymethyl
cellulose
• Mechanism of Pseudoplasticity:
• Pseudoplastic behavior arises from a shearing
action on long-chain molecules, Increased
shearing stress causes these molecules to align in
the direction of flow  reducing internal
resistance and releasing solvent associated with
the molecules, further lowering viscosity.
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Pseudoplastic flow
• The equation describing plastic flow is , where N > 1
• The exponent N rises as flow becomes increasingly non-Newtonian.
When N = 1, equation reduces to equation and flow is Newtonian.
• The term η′ is a viscosity coefficient. Following rearrangement, we can
write equation in the logarithmic form
• This is an equation for a straight line. Many pseudoplastic systems fit
this equation when log G is plotted as a function of log F.
• In case of pseudo plastic flow, N > 1. i.e. More N >1, the greater
pseudo plastic flow of material. If N = 1, the flow is Newtonian.
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Dilatant flow
• Certain suspensions with a high percentage of
dispersed solids exhibit an increase in resistance to
flow with increasing rates of shear. Such systems
actually increase in volume when sheared and are
hence termed dilatant.
• This type of flow is the inverse of that possessed by
pseudoplastic systems  Also called “shear-
thickening” system
• When stress is removed, a dilatant system returns to
its original state of fluidity.
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Dilatant flow
• The equation describing dilatant flow is , where N < 1
• N is always less than 1 and decreases as degree of dilatancy increases.
As N approaches 1, the system becomes increasingly Newtonian in
behavior.
• Substances possessing dilatant flow properties are invariably
suspensions containing a high concentration (about 50% or greater) of
small, deflocculated particles.

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Dilatant flow - Explanation
• At rest, particles are closely packed with less voids spaces, also amount of vehicle is
sufficient to fill the void volume  This leads particles to move relative to one another
at low rate of shear.

• So therefore, dilatant suspension can be poured from bottle because in these

condition it is fluid.
• As shear stress is increased, the bulk of the system expands or dilates; hence the term
dilatant  particles shows the open packing  leads to a significant increase in
interparticle void but the amount of vehicle is insufficient to fill this void space
resistance to flow increases as particles are no longer completely wetted, or
lubricated, by the vehicle  Finally system show the paste like consistency. 21
Dilatant flow – Processing
Precautions
1.Processing Challenges: While conventional processing
methods for dispersions containing solid particles involve the
use of high-speed mixers, blenders, or mills, these methods
may not be suitable for dilatant materials. High shear
conditions during processing can cause dilatant materials to
solidify, potentially damaging processing equipment.
2.Precautionary Measures: Given the risk of solidification
and equipment damage, appropriate precautions must be
taken during the processing of dilatant materials. Alternative
processing methods or modifications to traditional techniques
may be necessary to mitigate these risks effectively.

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 Thixotropy
• It is a phenomenon, defined as isothermal and
comparatively slow recovery, on standing of a material, of a
consistency lost through shearing.
• Rate of shear is progressively increased and plotted against
shear stress, different behaviors are observed depending
on the type of material.
• For Newtonian systems, the upcurve and downcurve are
superimposable if the rate of shear is reduced after reaching the
maximum.
• For non-Newtonian systems, the downcurve is often displaced to
the left of the upcurve, indicating lower consistency at any given
rate of shear.
• Thixotropic behavior can be shown by plastic and pseudo-
plastic system. 23
Thixotropy concept (Particle –
Particle interaction) (Gel – Sol –
Gel Transformation)
• Shear disrupts this structure, causing a gel-to-sol transformation and exhibiting
shear thinning.
• Upon stress removal, the structure starts to reform gradually through random
Brownian movement of particles.

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Thixotropy
• Rheograms obtained with thixotropic materials depend highly
on the rate of shear increase or decrease and the duration of
exposure to each shear rate.
• shear rate of a thixotropic material is increased in a constant
manner from point a to point b and is then-
• decreased at the same rate back to e  hysteresis loop abe
• held constant for time t1 seconds, shearing stress, and hence
consistency, would decrease to an extent depending on time of
shear, rate of shear, and type of  hysteresis loop abce.
• held at the same rate of shear for t2 seconds  hysteresis loop abcde.
• Rheogram of a thixotropic material is not unique but will
depend on rheologic history of the sample and approach used
in obtaining the rheogram  Important point for quantitative
measure of thixotropy.
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Measurement of Thixotropy
• The measure of area of hysteresis loop formed by
the up and down curves in a thixotropic materials
gives the value of thixotropic break down. This
value can be obtained by using a planimeter.
• First method:
• Sample is applied with a constant shear rate for t1
seconds results in formation of hysteresis loop abce. 𝑼 −𝑼
𝟏 𝟐
𝑩=
• Similarly, applying the shear rate for t2 seconds results 𝒕
𝐥𝐧 𝟐
𝒕𝟏
in formation of abcde.
• This behaviour can be used for calculating thixotropic
where U1 and U2 are the plastic
coefficient, B, which indicates the rate of break down viscosities of the two downcurves
with time at constant shear rate. 26
Measurement of Thixotropy
• Second method:
• Determine the structural breakdown due to
increasing shear rate
• Thixotropic co-efficient M, which indicates
loss in shear stress per unit increase in
shear rate, is obtained from where, U1 and
U2 are plastic viscosities, V1 and V2 are
maximum shearing rates.
• The value M will depend on the rate of
shear chosen.
𝑼𝟏 −𝑼 𝟐
𝑴= Where, U1 and U2 are the plastic viscosities for two separate
𝒗𝟐
𝐥𝐧 downcurves having maximum shearing rates of v1 and v2
𝒗𝟏
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Bulges
• Concentrated aqueous magma (gel) of bentonite
(10-15% w/w) produces a hysteresis loop with a
characteristic bulge in the up-curve as shown in
Fig.
• This may be due to the arrangement of
crystalline plates of bentonite in the form of
"house-of-cards structure" that causes the
swelling of bentonite magmas.
• This three-dimensional structure result in a
bulged hysteresis loop.
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Spurs
• Gel formulations containing procaine pencillin gel
shows a typical rheogram with a characteristic
spur-like protrusion. The spur represents a sharp
point of structural breakdown at low shear rate.
• The structure demonstrates a high yield or spur
value, Y, that traces out a bowed up-curve when
the three-dimensional structure breaks in the
viscometer.

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Negative Thixotropy (or) Anti-
thixotropy
• Increase in thickness or resistance to flow with increased
time of shear.
• Negative Thixotropy represents an increase rather than a
decrease in consistency on the downcurve. Example:
magnesia magma (1-10%).
• The down curve falls to the right of up curve and it
continuously thickened and finally reached equilibrium at
which the up and down curves overlapped each other.
• After reaching equilibrium the system was found to have
gel-like property and showed greater suspendability.
• When allowed to stand, however, the material returned
to its sol-like properties.
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Rheopexy
• Rheopexy is a phenomenon in which sol forms a gel more readily
when shaken gently or sheared than when allowed to form the gel
while the material is kept at rest.
• E.g. magnesia magma and clay suspensions
• In a rheopectic system, the gel is the equilibrium state.
• In anti-thixotropy, the sol is the equilibrium state.
• Antithixotropy should not be confused with dilatancy or rheopexy 
Dilatant systems are deflocculated and ordinarily contain greater than
50% by volume of solid dispersed phase, whereas antithixotropic
systems have low solids content (1%–10%) and are flocculated
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 Thixotropy in Formulation
• Thixotropy is a desirable property in liquid pharmaceutical systems. This property is
crucial for maintaining particles in a suspended state.
• Ideal systems should have high consistency in the container but pour or spread easily.
• Example: Gel preparation stored in a lamitube  Gel does not start flowing as we open the cap and
invert the tube  Only starts flowing upon the application of pressure  Reason behind this is
nothing but thixotropy (i.e., shear thinning).
• Well-formulated thixotropic suspensions resist settling in the container.
• Example: Same principle also applies for suspensions  At rest they have high viscosity and does not
allow the particles to settle down rapidly  upon shaking its viscosity gets reduced and can be easily
removed from the container.
• Thixotropy is beneficial for parenteral suspensions used in intramuscular depot therapy.
• Example: Concentrated procaine penicillin G parenteral suspension (40-70% w/v) in water has high
viscosity in rest  Structural breakdown that occurs when it passes through the syringe needle helps
in easy flowability  After the injection, it restores its consistency and forms a depot at the site of
injection which helps in maintaining the sustained levels of drug in the body. 32
Thixotropy in Formulation
• Thixotropic systems may experience changes over time, affecting
formulation adequacy.
• Monitoring thixotropic changes requires examining multiple
rheological parameters.
• Parameters such as plastic viscosity, hysteresis area, yield value, and spur
value are essential for studying thixotropic aging effects.
• Understanding thixotropy is crucial for ensuring pharmaceutical
product quality and efficacy.

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Determination of Rheologic
Properties
Selection of viscometer

Single point Multi point

e.g. Ostwald viscometer e.g. Cup and bob viscometer
Falling sphere viscometer Cone and plate viscometer

Principle: Shear stress α rate of shear. Principle: Viscosity determination at several rate of
Equipment works at single rate of shear shear to get the consistency curve

Application: Newtonian fluid Application: Non-Newtonian fluid

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Ostwald viscometer
• Ostwald viscometer (Capillary)
• Ostwald viscometers are mainly used to determine the
viscosity of the Newtonian fluids.
• These type of viscometers act under the influence of gravity.
• Principle:
• The time of flow of the liquid under test is compared with the
time required for a liquid of known viscosity (usually water) to
pass between the two marks.
• Therefore, the viscosity of the unknown liquid can be
determined from the following equation –
η1 and η2 are the viscosities of the unknown and the standard liquids,
ρ1and ρ2 are the respective densities of the liquids
t1 and t2 are the respective flow times in seconds, 35
 Ostwald viscometer
• Poiseuille's equation
• Previous equation is based on Poiseuille's equation for a liquid flowing through a
capillary tube.

• Where, r  radius of the inside of the capillary, t  time of flow, ΔP  pressure

head under which the liquid flows, l  length of the capillary, and V  volume of
liquid flowing.
• The radius, length, and volume of a given capillary viscometer are invariants and
can be combined into a constant K. Hence , equations can then be written as

• The pressure head ΔP depends on the density of liquid being measured,

acceleration due to gravity (g) and difference in heights of liquid in viscometers.

36
Ostwald viscometer
• Acceleration of gravity is constant, & if the levels in capillary are kept
constant for all liquids.
• If these constants are incorporate into the previous equation then,
viscosity of liquids may be expressed as:

• On division of above equations, we will get the equation

37
Falling sphere viscometer
• It is called as Hoeppler viscometer
• Principle:
• A glass or steel ball rolls down an almost vertical glass
tube containing the test liquid at a known constant
temperature. The rate at which a ball of a particular
density and diameter falls is an inverse function of the
viscosity of the sample.
• Construction:
• Glass tube position vertically. Constant temperature
jacket with Water circulation around glass tube.

38
Falling sphere viscometer
• Working:
• A glass or steel ball is dropped into the liquid & allowed to reach equilibrium with
temperature of outer jacket. The tube with jacket is then averted so that, ball at
top of the inner glass tube. the time taken by the ball fall between two marks is
measured, repeated process for several times to get concurrent results. For better
results select ball which takes NLT 30 sec to fall between two marks.

• where t is the time interval in seconds for the ball to fall between the two points
• Sb and Sf are the specific gravities of the ball and fluid, respectively, at the
temperature being used.
• B is a constant for a particular ball and is supplied by the manufacturer.

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Cup-and-Bob Viscometer
• In cup-and-bob viscometers, the sample is sheared in the
space between the outer wall of a bob and the inner wall
of a cup into which the bob fits.
• The various instruments available differ mainly in
whether the torque results from rotation of the cup or of
the bob.
• Couette type of viscometer:
• the cup is rotated.
• The viscous drag on the bob due to the sample causes it to
turn.
• The resultant torque is proportional to the viscosity of the
sample.
• e.g. MacMichael viscometer 40
Cup-and-Bob Viscometer
• Searle type of viscometer
• Stationary cup and a rotating bob.
• The torque resulting from the viscous drag of the system under examination is
generally measured by a spring or sensor in the drive to the bob.
• e.g. Stormer viscometer
• Working:
• The test sample is placed in the space between the cup and the bob  allowed to
reach temperature equilibrium. A weight is placed on the hanger  time recorded for
the bob to make 100 revolutions  these data converted to rpm. The weight is
increased and the whole procedure repeated.
• Rheogram constructed using rpm values and weight added.
• Convert the rpm values and weight values to shear rate and shear stress values by
using appropriate constants.
41
Cup-and-Bob Viscometer
• Apparent viscosity of a pseudoplastic system (by modified Stormer
viscometer)

• where Kv is a constant for the instrument, v is rpm generated by the weight,

w, in grams
• The equation for plastic viscosity when employing the Stormer
viscometer.

• where U is the plastic viscosity in poises, wf is the yield value intercept in

grams,
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Cone-and-Plate Viscometer
• Ferranti–Shirley viscometer is an example of a
rotational cone-and-plate viscometer
• Operation:
• Sample is placed at the center of the plate  which is
then raised into position under the cone. A variable-
speed motor drives the cone,  the sample is sheared
in the narrow gap between the stationary plate and the
rotating cone. The rate of shear in rpm is increased and
decreased by a selector dial and the viscous traction or
torque (shearing stress) produced on the cone.
• A plot of rpm or rate of shear versus shearing stress can
be constructed.
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Cone-and-Plate Viscometer
• The viscosity of a Newtonian liquid measured in the cone–plate viscometer is
calculated by use of the following equation-

• where C is an instrumental constant, T is the torque reading, and vis the speed of the
cone in rpm.
• For a material showing plastic flow, the plastic viscosity is given by the equation-

• where the yield value (f) is given by , where Tf is the torque at the shearing stress axis
(extrapolated from the linear portion of the curve) and Cf is an instrumental constant.
44
Deformation of
Solids
Deformation of Solids
• Deformation of solids:
• It is defined as change in the size and shape of an object upon Stress
application external force.
• It is defined from the concept of Strain and stress.
Deformation
• Stress (σ)
• It is the force per unit area that applies to an object to deform it.
• Stress (σ) = Force/Area Removal of Stress

• Its unit is Nm-2 or Pa

• Strain Elastic
Deformation
• It is the measure of the amount of deformation.
• Example- If the Bar has original length(L) and when the load is applied
on a bar the length of bar will change which is indicated as (ΔL). Plastic
Deformation
• Strain (ε) = ΔL /L
• It has no unit. 46
Elastic deformation
• Introduction
• During initial compression, materials deform elastically.
• The change in shape due to applied pressure is reversible.
• The specimen returns to its original shape upon release of
pressure.
• Hooke's Law:
• This law states that “In an elastic member, stress (σ) is directly proportional to
strain (ε) within the elastic limit".
• σ = Eε, where E is Young's Modulus of Elastic Modulus.
• ε = (l-lo)/lo, where lo is the initial length and l is the final length.

47
Elastic Modulus
• Elastic modulus (E) is the proportionality constant depends on the
material being deformed and the nature of the deformation.
• Elastic modulus determine the amount of force required per unit
deformation.
• E =σ/ε
• Long elastic modulus material is difficult to deform
• Small elastic modulus is easy to deform

48
Elastic deformation
• The relationship indicates that the slope
of stress vs. strain curve can be used to
find the elastic or young modulus E.
• The elastic range ends when the
material reaches its yield strength.
• At this point plastic deformation begins.

49
Plastic deformation
• Plastic deformation is the permanent change
in shape of a specimen due to applied stress.
• The onset of plastic deformation is seen as
the change of curvature in the stress–strain
curve.
• Transition from elastic to plastic is
characterized by yield strength of the material
• Plastic deformation is important because it
permits pharmaceutical excipients and drugs
to establish large true areas of contact during
compaction. In this way, strong tablets can be
prepared.
50
Heckel Equation
• Relationship between relative density (D) and compression pressure
(P).
• D = ρS/ρA, where ρS is the density of the powder or compact, and ρA
is the absolute density of the material.
• D ranges from 0.4 to 0.95 for loose powders and highly compacted
tablets.
• Porosity (ε) is inversely related to relative density: ε = 1 - D.
• Heckel Relationship:
• It is based on the assumption that the decreasing void space within the tablet
follows a first-order rate process.

• K (consolidation ability) is a constant that reflects the ability of the powder to

consolidate into a coherent mass.
51
• Heckel equation (Integrating above equation): ln(1/1 - D) = KP + A.
Heckel Equation
• Heckel Plot:
• A Heckel plot obtained by plotting ln(1/1 - D) vs. P
• Only the terminal portion of the plot is linear and
conforms to equation.
• Initial nonlinear region indicates significant particle
rearrangement and the Heckel equation does not
apply
• Different terminal slopes indicate different
deformation properties
• K is the slope of the Heckel equation and is a measure
of the plasticity of the material
• A greater slope indicates that the material has greater
plasticity and is more easily permanently deformed.

52
Heckel Equation
• Application:
• Help in understanding powder flow and compaction properties which is
crucial for tablet manufacturing.
• Ensuring consistent tablet quality and performance like disintegration and
dissolution.
• Making aesthetically pleasing and robust tablet such as a smooth, elegant
appearance without cracks or chips.

53
Pharmaceutical Areas in which
Rheology is Significant
• Fluids • Solids
• Mixing
• Particle-size reduction of disperse systems with • Flow of powders from hoppers
shear and into die cavities in tableting
• Passage through orifices, including pouring, into capsules during
packaging in bottles, and passage through encapsulation
hypodermic needles
• Fluid transfer, including pumping and flow • Packageability of powdered or
through pipes granular solids
• Physical stability of disperse systems
• 2. Quasi-solids • 4. Processing
• Spreading and adherence on the skin Conclusion:
• Production capacity of the
Rheology plays a crucial role in pharmaceutical
• Removal from jars or extrusion from tubes equipment
formulations.
• Capacity of solids to mix with miscible liquids • Processing
Understanding efficiency
rheologic behavior helps in formulating
• Release of the drug from the base
effective and stable products.
54
End

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