RHEOLOGY AND BIORHEOLOGY

Learning Objectives:
 Define rheology.
 Provide examples of fluid pharmaceutical products exhibiting various rheologic behaviors.
 Describe the application of rheology in the pharmaceutical science.
 Understand and define the different concepts in rheology.
 Appreciate the fundamentals of practical determination of rheologic properties using the four
types of viscometers.

Content Outline:
 Definition
 Classification of Rheologic Systems
 Thixothropy
 Determination of Rheologic Properties
 Application of Rheology in Pharmacy

Rheology
rheo – to flow; logos – science
Science of describing the flow and deformation of matter under stress.
Viscosity (η)
- the resistance of fluid to flow
- the higher the viscosity, the greater the resistance.

Significance
 formulation of medicinal and cosmetic creams, pastes and lotion.
 formulation in emulsion, suspension, suppositories and tablet coatings
 fluidity of solutions for injection
 in mixing and flow of materials, their packing into containers, their removal prior to use
(whether by pouring from a bottle, extrusion from a tube or passage through a single syringe
needle).
 affect patient acceptability, physical stability and even biological availability.

Classification of Rheologic Systems

 Newtonian System
 Non-Newtonian System

Newtonian System:

Newton’s Laws:
1. Everybody continues in its state of rest or uniform motion in a straight line unless it is acted
upon by another force.
2. The rate of change of momentum is proportional to the applied force and in the direction of the
applied force.
3. For every action there is equal and opposite reaction.

Definitions:
  Shear - the movement of material relative to parallel layer
 Shear Stress (F) - the force per unit area required to bring about a flow
 Shear rate (G) - the difference in velocity (dv) between two planes of liquids separated by
distance (dr)

The rate of shear should be directly proportional to the shearing stress.

=
Where:
F’/A = force per unit time
η = coefficient of viscosity or “viscosity”
dv = difference of velocity
dr = infinitesimal distance
dv/dr = velocity gradient or rate of shear

* 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.
• • •
= ∴ = ∴ = = = = [ ]
• • /
• •
= = [ ]
•

* the unit for viscosity is poise or for convenience centipoise (cp, cps). 1 poise = 100 centipoise
Poise - the shearing force 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.

Fluidity is a term sometimes used, is defined as the reciprocal of viscosity: Ø = 1/η

Flow curve for Newtonian flow.

 USP viscosity at 20oC

 Kinematic Viscosity - the absolute viscosity divided by the density of liquid at a specific
temperature
Kinematic viscosity = η/ρ
Where:
ρ = the density of the liquid
* The unit is Stoke(s) or centistoke(cs).

 Relative Viscosity - the relation of the solution viscosity η to the viscosity of the solvent
“standard” ηo.
Relative viscosity = ηrel = η/ηo

Temperature and viscosity:

Whereas the viscosity of a gas increases with temperature, that of a liquid decreases as temperature is
raised, and the fluidity of a liquid (the reciprocal of viscosity) increases with temperature.

Non-Newtonian Systems:

Non-Newtonian fluid - one in which the relationship between shear stress and shear rate is not a
constant
 When the shear rate is varied, the shear stress doesn’t very in the same proportion. The
viscosity of such fluids will therefore change as the shear rate is varied.
 Seen in liquid and solid heterogenous dispersions such as colloids, emulsions, liquid suspension
and ointments.

Three Classes:
 1. Plastic Flow 2. Pseudoplastic Flow 3. Dilatant Flow

Plastic Flow
 known as Bingham bodies
 a Bingham body does not begin to flow until a shearing stress corresponding to the yield value is
exceeded.
 Yield value (f) is an indication of the force that must be applied to a system to convert it to a
Newtonian System.
- an indication of the force of flocculation
- the more flocculated the suspension, the higher will be the yield.
 at stresses below the yield value, the substance acts as elastic material.
 substances that exhibit a yield value – solid
 substances that begin to flow at the smallest shearing stress and show no yield – liquid
 Plastic flow is associated with the preparation of flocculation and aggregation of particles in
concentrated suspension.
 The slope of the rheogram is termed mobility, analogous to fluidity in Newtonian system and its
reciprocal is known as Plastic Viscosity (U).
−
=

Pseudoplastic Flow
 known as shear-thinning
 the curve begins at the origin, there is no yield value occurs in dispersion of polymers (synthetic
or natural gum)
 As the shearing-stress is increased, disarranged molecules orient themselves to the direction of
 flow. This orientation reduces internal friction and resistance of the molecules an allows a
greater rate of shear at each stress.

Dilatant Flow
 known as shear-thickening
 certain suspension with a high percentage of dispersed solids exhibit an increase in resistance to
 flow with increasing rates of shear.
 system has increase in volume when sheared and hence – DILATANT.
 type of flow is the inverse of the flow properties possessed by the pseudoplastic system.
  when stress is removed, a dilatant system returns to its original state of fluidity.

Reasons for Dilatancy

1. At rest particles are closely packed with minimal inter-particle volume (void), so the amount of
vehicle to fill in voids and permits particles to move at low rate of shear.
2. Increase shear stress, the bulk of the system expand (dilate) and the particles take an open form
of packing.
3. The vehicles become insufficient to fill the voids between particles. Accordingly, particles are no
longer completely wetted (lubricated) by the vehicle.
4. Finally, the suspension will set-up as a firm paste.
5. This process is reversible.

Characteristics of Dilatant System

Resting Sheared
Closed packed particles Open packed particles
Minimum void volume Relatively low consistency
Relatively high consistency Increased void volume
Insufficient vehicle

Significance of Dilatancy
 Suggests appropriate precautions used during the processing of dilatant materials.
 Mixing (powder + granulating liquid) is usually conducted in high speed mixers, dilatant
materials may solidify under these conditions thereby damage the equipment.

THIXOTROPY
The decrease in viscosity as a function of time upon shearing, then recovery of original viscosity as a
function of time without shearing.
 The system contains asymmetric particles forming a loose network through sample.
 At rest, this structure impart rigidity to system resembling gel.
 As shear is applied, the structure begins to break and the material undergo Gel-to-Sol
transformation and exhibit shear thinning.
 Finally, at rest the structure is restored again Sol-to-Gel.

Thixotropic samples
 ketchup, paints, yoghurt, mayonnaise
 suspension
 emulsion, lotions, creams and ointments

Measurement of Thixotropy (2 approaches):

 (1st) To determine structural breakdown with time at constant rate of shear
 (2nd) To determine the structural breakdown due to increasing shear rate.

First:
1− 2
=
2
1
Where:
 B = thixotropic coefficient
U1, U2 = plastic viscosities; computed under plastic flow
t1, t2 = shearing rate constant (time), seconds

Second:
1− 2
=
2
ln( )
1
Where:
M = in dynes sec/cm2
U1, U2 = plastic viscosities
V1, V2 = maximum shearing rate of U1 and U2, respectively
t1, t2 = shearing rate constant (time), seconds

Negative Thixitropy
An increase in viscosity with time

Rheopexy
Solid forms a gel more readily when gently shaken or sheared than allowed to form a gel while the
materials are kept.

Rheopectic system – gel is the equilibrium form

Antithixotropy – sol is the equilibrium form

Determination of Viscosity:
1. Newtonian System
- Capillary viscometer
- Falling – Sphere viscometer
2. Newtonian and Non-Newtonian System
- Cup-and-Bob viscometer
- Cone-and-Plate viscometer

Capillary Viscometer
 also known as Ostwald viscometer
 determined by measuring the time required for the liquid to pass between two marks as it flows
by gravity through a vertical capillary tube
 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 2 marks.
=
Where:
= relative viscosity

Falling – Sphere Viscometer

 A glass or steel ball rolls down an almost vertical glass tube containing the test liquid at known
temperature.
 the rate at which a ball of particular density and diameter falls is an inverse function of the
viscosity of the sample.
  the time required for the ball to fall between two marks is accurately measured and repeated
several times.
= −
Where:
t = time interval in seconds for the ball to fall between two points
Sb, Sf = specific gravities of the ball and fluid, respectively
B = constant for a particular ball (manufacturer’s specs: 0.5 to 200,000 poise)
* ball to be used such that t is not less than 30 sec.

Cup-and-Bob Viscometer
 a sample is sheared in the space between the outer wall of a bob and the inner wall of a cup to
which the bob fits.
 popular instrument is the Stormer instrument.
o the test system is placed between the cup and the bob and allowed to make reach
temperature equilibrium.
o a weight is placed in the hanger and the time required for the bob to make 100
revolutions is recorded.
o the data is converted to revolutions per minute
o the weigh is increased and the whole procedure is repeated.
−
=
Where:
U = plastic viscosity
Wf – yield value intercept in grams
Kv = constant (reference oils)
V = rpm
W = grams

Cone Plate Viscometer

 Ferranti-Shirley, popular example
 the 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 and the sample is sheared in the narrow gap between
the stationary plate and the rotating cone
 the rate of shear in revolutions per minute is increased and decreased by a selector dial and the
viscous traction or torque (shearing stress) produced on the cone is read on the indicator scale.
Newtonian Liquid: =
Where:
C = instrument constant
T = torque reading
v = speed of the cone in revolutions per minute

Non-Newtonian Liquid: =
Tf = torque at the shearing stress axis
Cf = instrumental constant

Pharmaceutical Area in which Rheology is significant:

1. Fluids
 a. Mixing
b. Particle-size reduction of disperse system with shear
c. Passage through orifices, including pouring, packaging on bottles and passage through
hypodermic needles.
d. Fluid transfer, including pumping and flow through pipes
e. Physical stability of disperse system

2. Quasisolids
f. Spreading and adherence on the skin
g. Removal from jars or extrusion from tubes
h. Capacity of solids to mix with miscible liquids
i. Release of the drug from the base

3. Solids
j. Flow of powders from hoppers and into die cavities in tableting or into capsules during
encapsulation
k. packagability of powdered or granular solids

4. Processing
l. processing capacity of the equipment
m. processing efficiency