Here is my assignment on rheology. Hope it helps others on slide share ;)

1. UNIVERSITY OF MAURITIUS
Bachelor of Pharmacy – Year 2
PHARMACEUTICS III
TITLE:
‘To the pharmacist, rheology is important in
the flow of emulsions, through colloid mills,
triturating suspensions in mortar and pestle
and mechanical properties of glass or plastic
containers and of rubber closures’. Discuss.
Presented by:
NARAINO MAJIE Nabiilah - 1216824
Date of Submission: 29th April 2014

2. INTRODUCTION
Rheology is the science concerned with the deformation of matter under the influence of
stresses, which may be applied perpendicularly to the surface of a body (a tensile stress),
tangentially to the surface (a shearing stress), or at any other angle to the surface. The
deformations that result from the application of stress may be divided into two types:
1. Spontaneously reversible deformations or elastic deformations, and
2. Permanent or irreversible deformations that are referred to as flow and are exhibited by
viscous bodies.
The work used in producing an elastic deformation is recoverable when the body returns to
its original shape after removal of the applied stress. However, in irreversible deformations
the work used in maintaining deformation is dissipated as heat and is not recoverable
mechanically when the stress is removed.
From the rheological viewpoint systems are:
 Solid if they preserve shape & volume.
 Liquid if they preserve their volume.
 Gaseous if neither the shape nor volume remains constant when forces are applied to
them
The shear stress that causes a particular rate of shear is obtained by dividing the shearing
force by the area of the surface of the surface to which the shearing force is tangentially
applied. The ratio of the applied shear stress to the rate of shear is known as the coefficient of
viscosity. The simplest definition of viscosity is resistance to flow. Sir Isaac Newton defined it as
“the resistance that arises from lack of slipperiness in a fluid.” The effect of rate of shear on this ratio
varies for different systems which have led to these systems to be classified into the following
types:
1. Newtonian
Fluids which obey the Newton's law of viscosity are called as Newtonian fluids. Newton's
law of viscosity is given by
τ = μdv/dy ;
where τ = shear stress
μ = viscosity of fluid
dv/dy = shear rate, rate of strain or
velocity gradient

3. All gases and most liquids which have simpler molecular formula and low molecular weight
such as water, benzene, ethyl alcohol, CCl4, hexane and most solutions of simple molecules
are Newtonian fluids.
2. Non-Newtonian
Fluids which do not obey the Newton's law of viscosity are called as non-Newtonian fluids.
Generally non-Newtonian fluids are complex mixtures: slurries, pastes, gels, polymer
solutions etc.
Various non-Newtonian Behaviours:
Time-Independent behaviours:
These are properties are independent of time under shear.
 Bingham-plastic: Resist a small shear stress but flow easily under larger shear stresses.
e.g. tooth-paste, jellies, and some slurries.
 Pseudo-plastic: Most non-Newtonian fluids fall into this group. Viscosity decreases with
increasing velocity gradient. e.g. polymer solutions, blood. Pseudoplastic fluids are also
called as Shear thinning fluids. At low shear rates (du/dy) the shear thinning fluid is more
viscous than the Newtonian fluid, and at high shear rates it is less viscous.
 Dilatant fluids: Viscosity increases with increasing velocity gradient. They are
uncommon, but suspensions of starch and sand behave in this way. Dilatant fluids are also
called as shear thickening fluids.

4. Time dependent behaviours:
These are properties which are dependent upon duration of shear.
 Thixotropic fluids: for which the dynamic viscosity decreases with the time for which
shearing forces are applied. e.g. thixotropic jelly paints.
 Rheopectic fluids: Dynamic viscosity increases with the time for which shearing forces
are applied. e.g. gypsum suspension in water.
 Visco-elastic fluids: Some fluids have elastic properties, which allow them to spring back
when a shear force is released. e.g. egg white.
In manufacturing, having a complete rheological understanding of the material being
processed is important to verify the equipment can effortlessly handle the job and perform it
in an accurate and reproducible manner.
In pharmaceutical industries, rheology is involved in the study of viscosity is of true liquids,
solutions, dilute and concentrated colloidal systems. It is also involved in the mixing and flow
of materials, their packaging into containers, and the pouring from the bottle, extrusion from
a tube or a passage of the liquid to a syringe needle. It can affect the patient’s acceptability of
the product, physical stability, biologic availability, absorption rate of drugs in the
gastrointestinal tract and influence the choice of processing equipments in the pharmaceutical
system.

5. IMPORTANCE OF RHEOLOGY IN SUSPENSIONS
The rheological properties of suspensions are markedly affected by the degree of
flocculation. The reason for this is that the amount of free continuous phase is reduced, as it
becomes entrapped in the diffuse floccules. Consequently, the apparent viscosity of a
flocculated suspension is normally higher than that of a suspension which is in all ways
similar, with the exception that it is deflocculated.
In addition, when a disperse system is highly flocculated then the possibility of interaction
between floccules occurs and structured systems result. If the forces bonding floccules
together are capable of withstanding weak stresses then a yield value will result, and below
this value the suspension will behave like a solid. Once the yield value has been exceeded the
amount of structural breakdown increases with increased shear stress. Therefore, flocculated
suspensions will exhibit plastic or, more usually, pseudoplastic behaviour. Obviously, if the
breakdown and reformation of the bonds between floccules is time dependent then
thixotropic behaviour will also be observed.
The formation of structures does not occur in deflocculated suspensions and so their
rheological behaviour is determined by that of the continuous phase together with the effect
of distortion of the flow lines around the particles; in this situation the
Einstein equation may apply. The equation is as follow:
r
 +2.5 
As the suspension becomes more concentrated and the particles come into contact, then
dilatancy will occur.
Many pharmaceutical products, particularly those for children, are presented as suspensions
and their rheological properties are important. In general these properties must be adjusted so
that:
1. The product is easily administered (e.g. easily poured from a bottle or forced through a
syringe needle);
2. Sedimentation is either prevented or retarded; if it does occur, redispersion is easy;
3. The product has an elegant appearance.
Deflocculated particles in Newtonian vehicles
When such systems sediment, a compact sediment or cake is produced which is difficult to
redisperse. The rate of sedimentation can be reduced by increasing the viscosity of the
continuous medium, which will remain Newtonian. However, there is a limit to which this
viscosity can be increased because difficulty will be experienced, for example, in pouring the

6. suspension from a bottle. Furthermore, if sedimentation does occur, then subsequent
redispersion may be even more difficult.
Deflocculated particles in non-Newtonian vehicles
Only pseudoplastic or plastic dispersion media can be used in the formulation of suspensions
and both will retard the sedimentation of small particles, as their apparent viscosities will be
high under the small stresses associated with sedimentation. Also, as the medium will
undergo structural breakdown under the higher stresses involved in shaking and pouring, both
these processes are facilitated.
The hydrocolloids used as suspending agents, such as acacia, tragacanth, methylcellulose,
gelatine and sodium carboxymethylcellulose, all impart non- Newtonian properties -
normally pseudoplasticity -to the suspensions. Thixotropy can occur and this is particularly
the case with the mineral clays, such as bentonite (which must only be used in suspensions
for external use). The three-dimensional gel network traps the deflocculated particles at rest
and their sedimentations retarded and may be completely prevented. The gel network is
destroyed during shaking so that administration is facilitated. It is desirable that the gel
network is reformed quickly so that dispersion of the particles is maintained.
Flocculated particles in Newtonian vehicles
Such particles will still sediment, but because the aggregates are diffuse a large volume
sediment is produced and, as such, is easier to disperse. These systems are seldom improved
by an increase in the viscosity of the continuous phase as this will only influence the rate of
sedimentation. The major problem is one of pharmaceutical inelegance, in that the sediment
does not fill the whole of the fluid volume.
Flocculated particles in non-Newtonian vehicles
These systems combine the advantages of both methods. Furthermore, variations in the
properties of the raw materials to be suspended are unlikely to influence the performance of a
product made on production scale. Consequently, less difference will be observed between
batches made by the same method and plant.

7. IMPORTANCE OF RHEOLOGY IN EMULSIONS
Emulsions consist of droplets of one liquid dispersed in another immiscible liquid. The
rheology of emulsions has many similar features to that of suspensions. However, they differ
in three main aspects:
(i) The mobile liquid/liquid interface that contains surfactant or polymer layers introduces a
response to deformation and one has to consider the interfacial rheology,
(ii) The dispersed-phase viscosity relative to that of the medium has an effect on the rheology
of the emulsion,
(iii) The deformable nature of the dispersed-phase droplets, particularly for large droplets, has
an effect on the emulsion rheology at high phase volume fraction, φ.
Because nearly all but the most dilute of medicinal emulsions exhibit non-Newtonian
behaviour, their rheological characteristics have a marked effect on their usefulness. The fluid
emulsions are usually pseudoplastic, and those approaching a semisolid nature behave
plastically and exhibit marked yield values. The semisolid creams are usually viscoelastic.
A considerable variety of pharmaceutical products can be formulated by altering the
concentration of the disperse phase and the nature and concentration of the emulsifying agent.
The latter can be used to confer viscoelastic properties on a topical cream merely by varying
the ratio of surface-active agent to long-chain alcohol.
Factors that affect rheology of emulsions
These factors are:
 The volume fraction of the disperse phase,
 The viscosity of the disperse droplets,
 The droplet size distribution,
 The viscosity and chemical composition (ph, electrolyte concentration, etc.) Of the
medium,
 The interfacial rheology of the emulsifier film and
 The concentration and nature of the emulsifier.
Viscosity of the continuous phase
It has been well documented that a direct relationship exists between the viscosity of an
emulsion and the viscosity of its continuous phase. Syrup and glycerol, which are used in oral
emulsions as sweetening agents, will increase the viscosity of the continuous phase. Their
main disadvantage is in increasing the density difference between the two phases, and thus
possibly accelerating creaming. Hydrocolloids, when used as emulsifying agents in o/w

8. emulsions, will stabilize them not only by the formation of multimolecular layers around the
dispersed globules, but also by increasing the continuous phase viscosity. They do not have
the disadvantage of altering the density of this phase. If oil is the continuous phase, then the
inclusion of soft or hard paraffin or certain waxes will increase its viscosity.
Viscosity of the dispersed phase
For most practical applications it is doubtful whether this factor would have any significant
effect on total emulsion viscosity. It is possible, however, that a less viscous dispersed phase
would, during shear, be deformed to a greater extent than a more viscous phase, and thus the
total interfacial area would increase slightly. This may affect double-layer interactions and
hence the viscosity of the emulsion.
Nature and concentration of the emulsifying system
It has already been shown that hydrophilic colloids, as well as forming multimolecular films
at the oil/water interface, will also increase the viscosity of the continuous phase of an o/w
emulsion. Obviously, as the concentration of this type of emulgent increases so will the
viscosity of the product. Surface-active agents forming condensed monomolecular films will,
by the nature of their chemical structure, influence the degree of flocculation in a similar
way, by forming linkages between adjacent globules and creating a gel-like structure. A
flocculated system will exhibit a greater apparent viscosity than its deflocculated counterpart
and will depend on surfactant concentration.
RHEOLOGICAL SIGNIFICANCE ON PROPERTIES OF CONTAINERS OF
SUSPENSIONS AND EMULSIONS
Typical liquid-based oral dosage forms are elixirs, emulsions, extracts, fluidextracts,
solutions, gels, syrups, spirits, tinctures, aromatic waters, and suspensions. These products are
usually non sterile but may be monitored for changes in bio burden or for the presence of
specific microbes. These dosage forms are generally marketed in multiple-unit bottles or in
unit-dose or single-use pouches or cups. The dosage form may be used as is or admixed first
with a compatible diluent or dispersant. A bottle is usually glass or plastic, often with a screw
cap with a liner, and possibly with a tamper-resistant seal or an overcap that is welded to the
bottle. The same cap liners and inner seals are sometimes used with solid oral dosage forms.
A pouch may be a single-layer plastic or a laminated material. Both bottles and pouches may
use an overwrap, which is usually a laminated material. A single-dose cup may be metal or
plastic with a heat-sealed lid made of a laminated material. A liquid-based oral drug product

9. typically needs to be protected from solvent loss, microbial contamination, and sometimes
from exposure to light or reactive gases (e.g., oxygen).
Container-closures (or 'stoppers' or 'bungs') are an important part of the final packaging for
pharmaceutical preparations, particularly those which are intended to be sterile. The most
commonly used type of stopper is an 'elastomeric' container-closure. An elastomer is any
material that is able to resume its original shape when a deforming force is removed (this is
known as viscoelasticity).
Before using a container-closure in a vial or bottle with a drug product, the container-closure
must be assessed to determine if it is suitable for use with the product that will be filled into
the glass container. The user should consider the following questions relating to product
compatibility, in conjunction with the manufacturer of the container-closure:
 Is the product absorbed by the rubber?
 Does the rubber react with the product and leach out impurities?
 At which temperature range are the closure and product stable?
 How effective is the seal integrity?
 What happens when the product and stopper are stored together over time (a stability
trial)?
Once these questions have been satisfactorily answered, the user can work with the
manufacturer to design the optimal container-closure for the vial design and product.
REFERENCES
1. David J Mastropietro, Rashel Nimroozi and Hossein Omidian, 2013, Rheology in
Pharmaceutical Formulations-A Perspective, Journal of Developing Drugs, Volume 2,
Issue 2. Available at: http://www.omicsgroup.org/journals/rheology-in-pharmaceutical-formulationsa-
perspective-2329-6631.1000108.pdf
2. Tharwat F. Tadros, 2013, Emulsion Formation, Stability, and Rheology, Wiley online
journals. Available at: http://www.wiley-vch.de/books/sample/3527319913_c01.pdf
3. Anon, 2014, Newtonian and non-Newtonian Fluids, Online. Available at:
http://www.msubbu.in/ln/fm/Unit-I/NonNewtonian.htm
4. Dr. Sandle, 2013, Container-Closures for Pharmaceutical Preparations, Online. Available
at:
http://www.mypharmacareers.com/pharmajournal/articles/container_closures_for_pharma
ceutical_preparations.html
5. Guidance for Industry, 1999, Container Closure Systems for Packaging Human Drugs
and Biologics, Online Book. Available at:
http://www.fda.gov/downloads/Drugs/Guidances/ucm070551.pdf