Transcript Rheology 7

Rheology
Rheology
Rheology is the branch of physics which deals
with deformation and flow of matter.
The term rheology keerG morf ,rheo )wolf ot(
dnalogy (science).
This term was used to describe the flow of liquids
and the deformation of solids.
Rheology
Viscosity : ot diulf a fo ecnatsiser eht fo noisserpxe na si
wolf;
the higher the viscosity, the greater the resistance.
Rheology ecneics eht sa denifed eb yam that concerned
with the deformation of matter under the influence of
stress, which may be applied perpendicularly eht ot
ydob a fo ecafrus(tensile stress), tangentially eht ot
ydob a fo ecafrus(shearing stress), or at any other angle
to the surface of the body .
There are two extremes of rheological behavior:
i) Elastic behavior—which refers to the ability of a
formulation to restore its original shape when the
external force is removed.
It is a spontaneous and reversible deformation.
Exhibited by elastic bodies.
ii) Viscous (or plastic) behavior, which is known as a
property of ideal Newtonian liquids, where any
deformation ceases when the applied force is
removed.
It is a permanent or irreversible deformation.
Plastic deformation is exhibited by viscous bodies.
Most viscoelastic materials lie between elastic and viscous
behavior.
Rheology is important in pharmaceutical science.
The flow properties influence each step of the pharmaceutical
development processes, such as:
1.
2.
3.
4.
Filling.
Mixing.
Packing.
Removal of a substance from the
container, extrusion from a tube, or
passage through a syringe needle.
The rheology of a particular product (which can range in
consistency from fluid to semisolid to solid) can affect:
1.
patient acceptability of the product.
2.
physical stability of the product
3.
biological availability of the product .
NEWTONIAN’S LOW OF FLOW
 Let us consider a block of liquid consisting of parallel plates of
molecules as shown in the figure (1).
 The bottom layer is considered to be fixed in place.
 If the top plane of liquid is moved at constant velocity, each
lower layer will move with a velocity directly proportional to
its distance from the stationary bottom layer
Figure (1): Representation
of shearing force acting on
a block of material
 Rate of Shear, G = dv/dr
It is the velocity difference dv between two planes of
liquid separated by an infinite distance dr.
It is Indicates how fast a liquid flows when a stress is
applied on it.
 The Shearing Stress, F =F'/A
It is the force per unit area required to cause flow.
 Rheogram
The graph representing the flow property of a material is
termed as Rheogram.
To express the rheological properties of liquids graphs
showing the variation of shear rate with shear stress
(obtained by plotting shear rate, G, versus shear stress,
F)
 Assessment of Rheological Property of Materials
There are a number of ways to quantify the thixotropic
behaviour of materials. Among these methods,
viscometers or rheometers is considered one of the
best instruments used to assess rheological behaviour at
varying shear stress and shear rates.
Classification of Systems
A system is considered as either a Newtonian flow or nonNewtonian flow depending on whether viscosity is correlated
with the shear rate or not.
Type of systems
Newtonian systems
Non-Newtonian systems
Plastic
Pseudo plastic
Dilatant
Classification of Systems
• The liquids that follow Newtonian flow include water,
ethanol, benzene, ethyl ether, glycerin and castor oil.
• Whereas the liquids that follow non-Newtonian flow include
ointments, creams, gels, pastes, and clays.
1.
Newtonian systems
A system is said to have Newtonian flow behavior when its
viscosity is independent of shear rate and dependent upon
the composition of the liquid, temperature and pressure.
It is observed that viscosity decreases as the temperature increases,
whereas it increases with an increase in pressure.
The graphs representing the flow properties are termed as
Rheograms.
In case of Newtonian system the flow curve (shear stress vs.
shear rate) is straight line passing through origin, indicating
that shear stress (τ) or the force per unit area (F/A) varies
directly with the shear rate as described in the following
equations.
 Newton recognized that:
The higher the viscosity of a liquid, the greater the force per
unit area (shearing stress) required to produce a certain rate of
shear.Thus, the rate of shear is directly proportional to the
shearing stress.
F'/A α dv/dr
F'/A = η dv/dr ……..(1)
where η is a constant known as
Viscosity
η = F / G…………...(2)
F = η G………..(3)
The slope of the line represents viscosity, which is defined as the
resistance to the relative motion of adjacent liquid layers.
The unit of viscosity is poise or dyne.sec.cm-2.
Poise
Is 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.
Centipoise (cp) = 0.01 Poise.
 Newtonian systems like water, simple organic liquids, true
solutions and dilute suspensions and emulsionssolutions and
dilute suspensions and emulsions
2.
Non-Newtonian systems
• As the name implies, there is a deviation from Newton's
relation between shear stress and the rate of shear.
• The viscosity of non-Newtonian fluids changes according to
the rate of shear, thus non-Newtonian systems have no
constant viscosity.
• non-Newtonian systems can be of three general types, such as
plastic, pseudo plastic and dilatants.
In case of plastic materials, it is observed that there is no flow
until it reaches the yield value as shown in the following
figure:
When stress above the yield value is
applied, they exhibit free flowing
liquid nature.
Materials exhibiting this type of flow
property are also termed as
Bingham Bodies.
Dilatant systems (also called as shear thickening agent) are
systems whose viscosity increases with an increase in the rate
of shear, as shown in the following Figure:
This property is exhibited by
dispersions containing high
percentage
of
small,
deflocculated particles, for
example:
clays,
slurries,
suspensions of starch in water,
aqueous glycerine or ethylene
glycol.
Fig. Effect of shear rate on the
viscosity of (A) Newtonian liquids,
(B) shear-thinning systems and (C)
shear thickening
The viscosity of the fluid varies with the shear stress and the
consistency depends upon:
The rate of shear.
The duration of shear (Time)
Time dependant behaviour
 Thixotropy is a term to describe an isothermal system in which
the apparent viscosity decreases under shear stress, followed by
a gradual recovery when the stress is removed.
 The opposite of thixotropic materials are rheopectic materials
which are materials that become more viscous as the duration of
applied force increases.
Thixotropy and rheopexy profiles (viscosity vs. time).
Because of the wide range applications of the thixotropic
properties in the field of pharmacy, formulations in
particular, it is essential to understand this complex
phenomenon utilized in the advanced formulations.
The factors affecting thixotropic
property
The phenomenon of thixotropy is influenced by several factors
like
1. pH,
2. temperature,
3. polymer concentrations,
4. polymer modification or combinations,
5. addition of cations or anions and excipients, such as lecithin,
sodium chloride and glycerol.
1. pH
• Due to wide variations in the pH value of the physiological
fluids, solution to gel (sol–gel) conversion induced by pH
changes seems to be an ideal approach for enhancement of the
pharmacological efficacies of the topical drug delivery,
especially ophthalmic and intravaginal applications.
1. pH
One of the most widely used polymers with thixotropical
property is polyacrylic acid (PAA) (Carbopol polymers),
whose aqueous solutions were less viscouse and acidic in
nature, and were transformed into gels upon increasing the
pH.
2. Temperature
Thermo-reversible gels can be used as a delivery system which
requires a sol–gel transition at body temperature.
For example, the viscosity of Poloxamer-407 (Pluronic F127)
is increased with temperature.
Poloxamers (Pluronics) are hydrophilic
non-ionic polymeric surfactant (triblock
copolymer) consisting of a central
hydrophobic block of polypropylene
glycol flanked by two hydrophilic
blocks of polyethylene glycol.
3. Concentrations of the polymer(s)
• The Poloxamer based system developed for the ophthalmic
drug delivery showed the strong concentration dependence of
sol–gel–sol conversion.
• A rheological property of binary hydroalcoholic gels made of
Carbopol and hyaluronic acid varied as a function of the
polymer concentration.
4. Polymer combinations
• An aqueous mixture of 1.5% HPMC and 0.3% PAA exhibited
the rheological characteristics that were similar to those of
2.0% PAA solution.
5. Addition of cat/anions
• An addition of cat/anions significantly affected the viscosity of
the thixotropic formulations.
• An incorporation of positively charged ions, such as Ca++, into
sodium alginate (SA) dispersions enhanced the viscosity and
shifted the flow type from Newtonian to a pseudo plastic flow
with thixotropic properties.
6. Addition of excipients
• An addition of excipients, such as lecithin, sodium chloride
and glycerol, to the gel system significantly affected its
viscosity, producing viscous thixotropic gels with enhanced
stability of the system.
• Lecithin, a permeation enhancer, induced sol–gel conversions
of Poloxamer 407 gels through the formation of micellar
structures and affected in vitro permeation rate of
triamcinolone acetonide.
Pharmaceutical applications of
thixotropy
The time-dependent change in viscous nature of thixotropy finds
its major applications in pharmaceutical formulations
including:
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•
•
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Hydrogel,
Ointment,
Suspensions, and
Emulsions.
Through various routes including:
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Oral,
Topical,
Ophthalmic, and
Mucosal administration.
1. Ophthalmic formulations
The conventional ocular drug delivery systems like solutions,
suspensions and ointments showed drawbacks,
such as
•Increased pre-corneal elimination,
•High variability in efficiency
•Blurred vision.
Various formulations including gels and nanoparticles with
thixotropic property have been developed as an ophthalmic
drug delivery system to address these drawbacks.
• It was reported that aqueous PAA gels administered into rabbit
eyes could be retained for 4–6 h and resulted in a longer
duration and greater activity of incorporated pilocarpine
compared with viscous drug solutions.
2. Parenteral formulations
• It is of strong interest for biomedical field to develop a
hydrogel which is able to pass through a needle without losing
its structure.
• An ideal thixotropic liquid should have high consistency under
the storage conditions yet being removed easily.
2. Parenteral formulations
• In one study, 50% hydrogels made of hyaluronane and alginate
were formulated, their thixotrophic behavior was verified, and
their mechanical properties were determined before and after
the passage through the needle.
• The unique property of these gels to flow like a liquid with
thixotropic behavior allowed them to be used as an injectable
hydrogel drug delivery system for various bioactive agents
(drugs, proteins, vaccines or plasmid DNAs).
3. Nasal formulations
• The major limiting factor for drug delivery to the nasal mucosa
has been the mucociliary clearance.
• It was reported that thixotropic solutions containing
methylcellulose derivatives lowered the clearance rate and
enhanced the bioavailability of the drugs administered through
the nose.