RHEOLOGY

The term “rheology,” from the Greek rheo (“to flow”) and logos (“science”), was suggested
by Bingham and Crawford (as reported by Fischer1) to describe the flow of liquids and the
deformation of solids.
Viscosity is an expression of the resistance of a fluid to flow; the higher the viscosity, the
greater is the resistance.

IMPORTANCE & FUNDAMENTALS

1. Formulation of medicinal and cosmetic creams, pastes and lotions.
2. Formulation of emulsions, suspensions, suppositories, and tablet coating.
3. Fluidity of solutions for injection and Passage of the liquid through syringe needle.
4. In mixing and flow of materials, their packaging into the containers, their removal
prior
to use, the pouring from the bottle.
5. Extrusion of a paste from a tube .
6. Influence the choice of processing equipments in the pharmaceutical system
NEWTONIAN LAW OF FLOW
Newton’s law of flow states that the application of stress on a liquid leads to flow in the direct
proportion to the amount of stress applied. The constant that relates the flow of a liquid to the
applied stress is called viscosity, η.
If the bottom layer is fixed in place and the top plane of liquid is moved at a constant
velocity, each lower layer will move with a velocity directly proportional to its distance. from
the stationary bottom layer.
The difference of velocity, dv, between two planes of liquid separated by an infinitesimal
distance, dr, is the velocity gradient or rate of shear, dv/dr.
The force per unit area, F /A, required to bring about flow is called the shearing stress and is
given the symbol F.
Newton was the first to study flow properties of liquids in a quantitative way. He recognized
that the higher the viscosity of a liquid, the greater is the force per unit area (shearing stress)
required to produce a certain rate of shear. Rate of shear is given the symbol G. Hence, rate
of shear should be directly proportional to shearing stress, or

where η is the coefficient of viscosity- as viscosity

where F = F /A and G = dv/dr. A representative flow curve, or rheogram

The unit of viscosity is the poise.

Fluidity, φ is defined as the reciprocal of viscosity.

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

The units of kinematic viscosity are the stoke (s) and the centistoke (cs).

Temperature Dependence and the Theory of Viscosity

Viscosity of a gas increases with the increase of temperature. Viscosity of liquid decreases as
the temperature is raised & the fluidity of a liquid, increases with 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 is a constant depending on the molecular weight and molar volume of the liquid and
Ev is an “activation energy” required to initiate flow between molecules.
NON-NEWTONIAN SYSTEMS
The majority of fluid pharmaceutical products do not follow Newton's law of flow. These
systems are referred to as non-Newtonian. Non-Newtonian behavior is generally exhibited by
liquid and solid heterogeneous dispersions.
Plastic Flow
 Plastic flow curves do not pass through the origin
 intersect the shearing stress axis (or will if the straight part of the curve is extrapolated
to the axis) at a particular point referred to as the yield value.
 A Bingham body 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. A plastic
system resembles a Newtonian system at shear stresses above the yield value.
 The slope of the rheogram is termed the mobility, analogous to fluidity in Newtonian
systems, and its reciprocal is known as the plastic viscosity, U.

where f is the yield value, or intercept, on the shear stress axis in dynes/cm2.

 Viscosity of a plastic substance decreases with increasing rate of shear- so called as

shear thinning system
 Example: Plastic flow is associated with the presence of flocculated particles in
concentrated suspensions. In which a continuous structure is set up. The yield value
is present due to contacts between adjacent particles brought about by Van der Waal's
forces consequently, the yield value is an indication of the force of flocculation, the
more flocculated the suspension, the higher will be the yield value. Beyond yield
value, particles become separate and starts flowing like a newtonium fluid.

Pseudo plastic flow

Liquid dispersion of natural and synthetic gums shows pseudo plastic flow. The curve for a
pseudoplastic material begins at the origin or at least approaches it at low rates of shear.
  The curved rheogram for pseudoplastic materials is due to shearing action on the long
chain molecules of materials such as linear polymers.
 In contrast to Bingham bodies, there is no yield value no part of the curve is linear,
one cannot express the viscosity of a pseudoplastic material by any single value.
 The apparent viscosity may be obtained at any rate of shear from the slope of the
tangent to the curve at the specified point

N = no. of given exponent

η = Viscosity coefficient
In case of pseudo plastic flow, N > 1.
More N >1, the greater pseudo plastic flow of material.
If N = 1, the flow is Newtonian.
Taking Log on both sides

Example:
1. Tragacanth in water
2. Sod. Alginate in water
 3. Methyl cellulose in water
4. Sodium CMC in water

 The curved rheogram for pseudoplastic materials results from a shearing action on the
long-chain molecules which become entangled and associated with immobilized
solvent.
 When shearing stress is applied the normally disarranged molecules begin to align
their long axes in the direction of flow.
 This orientation reduces the internal resistance of the material and allows a greater
rate of shear at each successive shearing stress.
 In addition, some of the solvent associated with the molecules may be released,
resulting in an effective lowering of the concentration and size of dispersed
molecules.
 An equilibrium exists between the shear induced changes and random coiling
tendency caused by Brownian motion which entraps water inside the coils.
 The viscosity decreases as the shear is increased, so they known as “shear thinning
systems

Dilatant flow
 Dilatant flow is usually seen in suspensions containing a high concentration (>50%)
of small, deflocculated particles. Exhibit an increase in resistance to flow with
increasing rates of shear. Systems increase in volume when sheared is termed as
dilatant.
 Dilatant materials are called shear-thickening systems.
  At rest: particles are closely packed and has minimum voids volume
 The Vehicle is sufficient to fill this void volume and allows the particles to move
relative to one another at low rates of shear. One can pour a dilatant suspension from a
bottle without shaking as it is relatively fluid without shear stress applied.
 If the shear stress is increased by shaking, the bulk expands or dilates as the particles
move quickly part from each other and take an open form of packing.
 Such an arrangement results in a significant increase in the void volume, with the
vehicle now being insufficient to fill the voids between the particles.
 The resistance to flow increases since the particles are no longer completely wetted or
lubricated by the vehicle and eventually the suspension will set up as a firm paste.

Caution must be taken in processing dilatant materials.

 Usually, the processing of dispersions containing solid particles is facilitated by the
use of high speed mixers, blenders or mills.
 Dilatant materials may solidify under these conditions of high shear, thereby
overloading and damaging the processing equipment.
THIXOTROPY
Thixotropy is defined as an isothermal and comparatively slow recovery, on standing of a
material, of a consistency lost through shearing.
If the rate of shear is reduced once the desired maximum is reached, the down-curve would
be superimposable on the up-curve. This is true for Newtonian systems.
 In case of non-Newtonian systems, the down-curve can be displaced relative to the up-curve.
With shear-thinning systems (pseudo plastic), the down-curve is frequently displaced to the
left of the
  Thixotropic systems usually contain asymmetric particles that, through numerous
points of contact, set up a loose three-dimensional network throughout the sample. At
rest, this structure confers some degree of rigidity on the system, and it resembles a
gel. As shear is applied and flow starts, this structure begins to break down as points
of contact are disrupted and particles become aligned. The material undergoes a gel-
to-sol transformation and exhibits shear thinning.
 On removal of stress, the structure starts to reform. This process is a progressive
restoration of consistency as asymmetric particles come into contact with Shearing
stress Rate of shear Pseudoplastic Plastic. Thixotropy in plastic and pseudoplastic
flow systems. one another by undergoing random Brownian movement.
 Rheograms obtained with thixotropic materials are therefore highly dependent on the
rate at which shear is increased or decreased and the length of time a sample is
subjected to any one rate of shear.

MEASUREMENT OF THIXOTROPY
Main characteristic of a thixotropic system is the hysteresis loop.
 The area of hysteresis has been proposed as a measure of thixotropic breakdown.
 Two approaches for plastic material.
1. Determine the structural breakdown with time at a constant rate of shear.
2. Determine the structural breakdown due to increasing shear rate.
• Limitations:
- Does not taken into account the shape of the up- and down-curves. So
- Two different materials may produce loops of similar area but which have
completely different shapes representing totally different flow behaviou
1. Determine the structural breakdown with time at a constant rate of shear
In which,
 The shear rate of thixotropic material is increased from a to b and then decrease at
same rate back to e.
 This results in Hysteresis loop abe.
 If the sample taken to point b & shear rate held constant for certain period of time (t1
sec.) then stress & consistency decrease to an extent depend on rate, time of shear &
str. of sample, results the Hysteresis loop abce.
 If sample held for same rate of shear for (t2 sec.), then loop abcde observed.

 Determine the structural breakdown due to increasing shear rate

 Application of thixotropy
o Thixotrophy is desirable property in emulsion and suspension
o Higher the thixotrophy, higher the physical stability of suspension.
o The degree of thixotrophy is related to the specific surface of penicillin used.
 o Thixotropy in formulation :Thixotropy is a desirable property in liquid
pharmaceutical systems that ideally should have: A high consistency in the
container yet pour or spread easily. a well formulated suspension will not settle
out readily in the container will become fluid on shaking and will remain so long
enough for a dose to be dispensed. will regain consistency rapidly enough so as to
maintain the particles in a suspended state.
o Also desirable with emulsions, lotions, creams, ointments and parenteral
suspensions to be used for intramuscular depot therap, eg: Concentrated parenteral
suspensions containing 40-70% w/v of procain penicillin G in water has high
inherent thixotropy . Break down of the structure occurres when passed through
the needle, Consistency was then recovered as rheologic structure reformed after
administration. Formulation of a depot of drug at the site of IM injection and drug
was slowly removed & made available to the body
 NEGATIVE THIXOTROPY OR ANTI THIXOTROPY: represents an increase
rather than a decrease in consistency on the downcurve. This increase in thickness or
resistance to flow with increased time of shear It was observed that when magnesia
magma was alternately sheared at increasing and then decreasing rates of shear, the
magma continuously thickened (an increase in shearing stress per unit shear rate) but
at a decreasing rate, and it finally reached an equilibrium state in which further cycles
of increasing-decreasing shear rates no longer increased the consistency of the
material.

Bulges and Spurs

Dispersions employed in pharmacy may yield complex hysteresis loops when sheared in a
viscometer in which shear rate (rather than shear stress) is increased to a point, then
decreased, and the shear stress is read at each shear rate value to yield appropriate rheograms.
Two such complex structures are Bulges and Spurs
A concentrated aqueous bentonite gel, 10% to 15% by weight, produces a hysteresis loop
with a characteristic bulge in the upcurve. It is presumed that the crystalline plates of
bentonite form a “house-of-cards structure” that causes the swelling of bentonite magmas.
This three-dimensional structure results in a bulged hysteresis loop.

In still more highly structured systems, such as a procaine penicillin gel for intramuscular
injection, the bulged curve may actually develop into a spur like protrusion.The structure
demonstrates a high yield or spur value, Υ, that traces out a bowed upcurve when the three-
dimensional structure breaks in the viscometer. The spur value represents a sharp point of
structural breakdown at low shear rate. thixotropic, forming intramuscular depots upon
injection that afforded prolonged blood levels of the drug