Rheology
By : Physical Pharmacy Team
The aim of study
Understanding of rheologi theory
Understanding the usefulness of rheologi in
pharmaceutical dosage forms
Understanding classification of materials
Rheology
Rheology is the science of flow and deformation of matter
and describes the interrelation between force, deformation
and time.
The term comes from Greek : rheos meaning to flow and logos
for science. It was suggested by Bingham & Crawford
Viscosity is an expression of the resistance of a fluid to flow;
viscosity , resistance.
Simple liquid can be described in terms of absolute viscosity.
Rheologic properties of heterogenous dispersions are more
complex & cannot be expressed by a single value
Rheology
Rheology is applicable to all materials, from gases to solids. It
is important in many fields to the physiologist, to the physician
and to the pharmacist
The importance of rheology in pharmacy & suggested its
application in :
the formulation and analysis of such pharmaceutical
product as emulsion, pastes, suppositories, & tablet
coatings.
manufacture of medicinal & cosmetic creams, pastes, and
lotions must be capable of producing product with
acceptable consistency and smoothness and reproducing
these qualities each time a new batch is prepared.
Rheology
The need for a proper understanding of the rheological
properties of pharmaceutical materials is an essential
fundamental to the preparation (selection of processing
equipment, mixing and flow of materials), their packaging into
container, and their removal prior to use (pouring from a
bottle, extrusion from a tube, passage through a syringe
needle), development and evaluation of pharmaceutical
dosage forms.
The rheological properties of raw materials and formulations can
cause problems during the manufacture of dosage forms in the
pharmaceutical, cosmetic, or food industry.
Exp : viscous materials require energy during mixing, the
viscosity might be by the application of heat in which could the
mixing time and improve product homogeneity, a viscosity of
suspensions could hence result in sedimentation might start to
leak
The rheological properties of pharmaceutical products are also
important with respect to patient compliance. Exp : stiff creams
might complicate their application or could cause pain the
patient will be more reluctant to use his medicine, suspensions and
emulsions should flow out of the bottle to allow easy metering
Classification of materials
Newtonian fluids
Non Newtonian fluids
Newtonian fluids
A Newtonian fluid will exhibit a linear relationship between
stress and shear rate and hence viscosity is independent of the
applied shear conditions. The viscosity of a Newtonian fluid is
dependent only on temperature but not on shear rate and time.
Examples:
Water
Sugar solution
Mineral oil, olive oil, castor oil
Gliserin, etanol
Aseton
Chloroform
Understanding
Shearing Stress and
Shearing Rate
What we actually see is that a velocity gradient (dv/dx) forms between the
two surfaces. It is this velocity gradient that gives us the Shear Rate.
The force F producing the deformation, or the equal and opposite restoring
force in the deformed solid, divided by the area A over which F is applied,
is called stress. In other words, the force per unit area required to bring
about flow is called Shearing Stress.
The viscosity or absolute viscosity or dynamic viscosity is quite simply the
ratio of the shear stress to the shear rate.
Newton was the first to study the flow properties of liquid in quantitative
way. He recognized that the higher the viscosities of a liquid, the greater
the force per unit area required to produce a certain rate of shear. Hence,
the rate of shear (D) should be directly proportional to the shearing stress
().
Understanding Shearing Stress and
Shearing Rate
This relationship can be written mathematically as:
F V
A X
The unit of viscosity is poise, defined as 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. The cgs units for the
poise are dyne sec cm-2 (that is, dyne sec/cm2) or g cm-1 sec-1 (that is, g/cm
sec). These units are readily obtained by a dimensional analysis of the
viscosity coefficient.
FX dynes cm dyne sec
Rearranging equation (4) to gives (5):
A V cm cm / sec
2
cm 2
dynes sec g cm / sec 2
sec g
This gives the result in equation (3):
2
2
cm cm cm sec
It is more convenient to employ a centipoise. 1 cp being equal to 0.01
poise.
Understanding Shearing Stress and Shearing Rate
Fluidity, (cm2/[Link]), a term sometimes used, is defined
as the reciprocal of viscosity:
1
In other words: it equals to the slope of the rheogram in
Newtonian System.
Kinematic Viscosity
The US Pharmacopoeia includes an explanation Kinematic
Viscosity, which is the absolute viscosity divided by the density
of the liquid at a definite temperature:
Kinematic Viscosity
The units for kinematic viscosity are stoke (s) and the
centistokes (cs).
Temperature Dependence and the Theory of Viscosity
While the viscosity of a gas with temperature, the viscosity
of liquids as the temperature, and the fluidity of a liquid
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:
AeEv / RT
Diintegralkan menjadi : ln = lnA + (Ev/R)(1/T)
in which A is a constant known as the Arrhenius factor or the
frequency factor, depending on the molecular weight and
molar volume of the liquid,
and Ev is an activation energy required to initiate flow
between the molecules (cal/mol), R is the gas constant (1.987
calories/mole.K), and T is the absolute temperature(0K).
Reogram Newtonian flow
D
D
= = F = Shear stress; D = G = Shear rate; = Viscosity Coefficient
Viscosity is independent of shear stress. It means that regardless of how
much force of agitation is applied to the liquid , it will have the same viscosity
value
Non Newtonian fluid
Most pharmaceutical fluids do not follow the Newton’s law
because the viscosity of the fluid varies with the rate of
shear. These materials are known as non-Newtonian
Non-Newtonian generally exhibited by liquid and solid
heterogeneous dispersions such as colloidal systems,
emulsions, suspensions, ointment and gels
Non Newtonian fluid
Time independent : Plastic, Pseudoplastic, and Dilatant.
Time dependent : Thixotropic (time thinning, i.e. viscosity
decreases with time), Rheopectic (time thickening, i.e.
viscosity increases with time)
Viscoelastic
Non-Newtonian fluid, time independent
Depending on how viscosity changes with shear rate the flow
behavior is characterized as:
Shear thinning: the viscosity decreases with increased shear rate.
Shear thickening: the viscosity increases with increased shear rate.
Plastic: exhibits a so-called yield value, i.e. a certain shear stress must
be applied before flow occurs.
Shear thinning fluids are also called pseudoplastic and
Shear thickening fluids are also called dilatant.
Plastic Flow
The curve represents a body that exhibits plastic flow; such
materials are known as Bingham bodies in honor of the pioneer of
modern rheology and the first investigator to study plastic
substances in a systematic manner.
The plastic flow curve doesn’t pass through the origin but rather
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 doesn’t begin to flow until a
shearing stress, corresponding to the yield value, is exceeded.
The rheologists classify Bingham bodies, that is, those substances
that exhibit a yield value, as solids, whereas substances that begin
to flow at the smallest shearing stress are defined as liquids.
Plastic Flow
Plastic flow is associated with the presence of flocculated particles in
concentrated suspensions. The yield value is present because of the
contact between adjacent particles, which must be broken down before
flow can occur.
Consequently, the yield value is an indication of the force of
flocculation: the more flocculated the suspension, the higher will be
the yield value.
A plastic system resembles a Newtonian system at shear stress above
the yield value
The slope of the rheogram of the plastic flow is termed mobility,
analogous to fluidity in Newtonian systems, and its reciprocal is known
as the plastic viscosity, U, the equation describing plastic flow is:
( f )
U
D
where: U= plastic viscosity in poise; f= yield value or intercept on the
shear stress axis in dyne/cm-2
Non-Newtonian flow: plastic
D
Yield value (f) D
= F = Shear stress; D = G = Shear rate; = Viscosity Coefficient
Pseudoplastic Flow
A large number of pharmaceutical products, including natural and
synthetic gums, e.g., liquid dispersions of tragacanth, sodium alginate,
methylcellulose, and sodium carboxymethylcellulose, exhibit
pseudoplastic flow.
As a general rule, pseudoplastic flow is exhibited by polymers in
solution, in contrast to plastic systems, which are composed of
flocculated particles in suspensions. From the curve (rheogram), a
pseudoplastic material begins at the origin (or at least approaches it at
low rates of shear).
These substances begin flow when a shearing stress is applied;
therefore, they exhibit no yield value. Consequently, in contrast to
Bingham bodies, there is no yield value.
Since however, no part of the curve is linear, one can’t express the
viscosity of a pseudoplastic material by any single value.
Pseudoplastic Flow
Aqueous sol of polymers (long-chain molecules) exhibit a
pseudoplastic rheologic profile. At rest or at low shear stress, the
polymers are in a coiled or globular conformation because of
intermolecular stabilizing forces. The immobilized water within this
globular conformation provides a three-dimensional structure to the
system and thus result in higher viscosity. When shear stress is applied
(such as agitation), the polimer chain untungles and expands in the
direction of flow. The viscosity of the solution decreases sharply as a
result of conformation change in the polimer and the release of water,
which leads to the breakdown of the structure.
Examples :
Paint
Shampoo
Printing inks
Non-Newtonian flow: pseudoplastic
Shear-thinning
D
D
= F = Shear stress; D = G = Shear rate; = Viscosity Coefficient
Dilatant Flow
Certain pastes & suspensions with a high percentage of dispersed
solids (about 50% or greater, the particle size needs to be below 50
µm, & the particles are deflocculated) 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. It should be immediately obvious that this
type of flow is the reverse of that possessed by pseudoplastic
systems.
To describe dilatancy in quantitative terms ⇒ FN = ’G
N less then 1 degree of dilatancy, N = 1 newtonian in
behavior
Examples of shear thickening fluids: Wet sand, Concentrated starch
suspensions , Whip Cream
→
istirahat rate of shear ↑
Partikel tersusun rapat Partikel tersusun longgar
Vol. kosong minimum [Link] meningkat
Pembawa cukup Pembawa tidak cukup
Konsistensi relatif rendah Konsistensi relatif tinggi
→rate of shear rendah, suspensi cair → suspensi bentuk pasta (kaku)
Dilatant Flow
Dilatant flow of suspension can become problematic
For example, during the industrial preparation of suspension,
the large mixing vessels provide a significant area to the
suspension product, which minimize shear stress. When the
suspension is prepared, it needs to flow through conduits that
transport it from the mixing vessels to the packaging area.
These conduits have a much smaller area than the mixing
vessels, and the shear stress increases substantially, it makes
the viscosity of the suspension increases and the product
cannot flow through
Non-Newtonian flow: dilatant
Shear-thickening
D
D
= F = Shear stress; D = G = Shear rate; = Viscosity Coefficient
Non Newtonian fluid
Time independent : Plastic, Pseudoplastic, and Dilatant.
Time dependent : Thixotropic (time thinning, i.e.
viscosity decreases with time), Rheopectic (time
thickening, i.e. viscosity increases with time)
Viscoelastic
Non Newtonian Fluids, Time Dependent
It was assumed that if the rate of shear was reduced once the
desired maximum rate had been reached, the down-curve would be
identical with the superimposed on the up-curve. While this is so
with Newtonian systems.
With the non-Newtonian systems, the down-curve can be displaced
with regard to the up-curve.
Non Newtonian Fluids, Time Dependent
With shear-thinning systems (i.e., Plastic and Pseudoplastic) the
down-curve is frequently displaced to the left of the up-curve,
showing that the material has a lower consistency at any one rate of
shear on the down-curve than it had on the up-curve.
This indicates a breakdown of structure (and hence shear thinning)
that does not reform immediately when the stress is removed or
reduced. This phenomenon, known as Thixotropy may be defined
as: an isothermal and comparatively slow recovery, on standing of a
material, of a consistency lost through shearing. As so defined,
thixotropy may be applied only to shear-thinning systems.
The viscosity of the fluid is dependent on temperature, shear rate
and time.
Thixotropy
Partikel asimetris menyusun kerangka tiga dimensi melalui
berbagai titik hubungan kekakuan pada keadaan diam;
menyerupai gel
Saat aliran dimulai (shear) struktur memecah krn titik
[Link] dan partikel lurus ; transformasi gel → sol
(koloid)
Struktur terbentuk kembali jika stress dihilangkan; proses
bertahap
Rheogram tergantung peningkatan laju dan penurunan
shear serta lama waktu bahan mengalami rate of shear
Pengukuran thiksotropik
Pendekatan pertama :
Loop histeresis (terbentuk antara
kurva menaik-menurun)
Koofisien thiksotropik (B), ditentukan
u bahan bingham bodies
U1 U 2
B
ln t 2
t1
U1,U2 : viskositas plastis kedua kurva menurun
t1, t2 : laju konstan setelah shearing
Metode : menentukan pecahnya struktur terhadap waktu
pada laju geser yang tetap (konstan)
Pendekatan kedua:
Metode : menentukan pemecahan stuktur akibat
meningkatnya rate of shear; 2 putaran histeresis yg memiliki
rate of share (v1, v2) yg berbeda
koofisien thiksotropik : M ([Link]/cm2)
2(U 1 U 2)
M
ln(v 2 v1) 2
Harga M tergantung rate of shear
yg dipilih scr sembarang
Bentuk loop histeresis
Reogram bentuk kembung “bulge” (gel
pekat bentonit 10 – 15% dlm air) diduga
sebagai perubahan struktur kristal
lempeng bentonit yang menyebabkan
magma bentonit mengembang
Reogram bentuk taji,
memberikan yield yang tinggi
(taji/spur value)Ý
Ý : titik tajam pemecahan
struktur pada shear rate yang
rendah; pengamatan saat
didiamkan; ditentukan dgn
viskometer cup and bob
Tiksotropi negatif (antitiksotropi)
Kurva turun berada di sebelah kanan dr kurva naik
kenaikan konsisten pd kurva turun
Kenaikan dlm hal kekentalan/hambatan mengalir dgn
bertambahnya waktu shear (co:magma magnesia)
Sistem antitiksotropi mgd zat padat terflokulasi 1 – 10%
Pd sistem ini jk diberi tekanan berganti-ganti pd kec geser yg
meningkat kemudian menurun, material akan terus
mengental pd keadaan keseimbangan
Keadaan keseimbangan yg didapat seperti gel dan
mempunyai kemampuan tersuspensi dgn baik & mudah
dituang, jk didiamkan akan kembali ke sifat solnya
Antitiksotropi disebabkan o/ frekuensi tumbukan dr partikel2
terdispersi/molekul2 polimer dlm suspensi ikatan antar partikel
dgn waktu terbentuk gumpalan2 yg relatif lbh besar, saat
keadaan diam/istirahat gumpalan tsb akan pecah gumpalan2
kecil & partikel2 tersendiri
Rheopectic
Gejala transformasi sol ke gel yg lebih cepat dgn pengadukan
perlahan (ada shear); gel adalah bentuk keseimbangan
antithiksotropik : sol dalam keseimbangan
Thixotropy in Formulation
idealnya adalah di dalam wadahnya sistem mempunyai
konsistensi yang tinggi namun mudah dituangkan. Misalnya,
suspensi tiksotropik yang diformulasikan dengan baik:
a. tidak akan mudah memisah di dalam wadahnya
b. akan menjadi encer bila dikocok
c. dan akan tetap demikian dalam tempo yang cukup lama sehingga
dosis yang akan diberikan tercapai
d. di dalam wadah konsistensinya akan cepat kembali lagi menjadi
tinggi sehingga partikel tetap dalam keadaan tersuspensi
Pola diatas sediaan emulsi, losio, krim, salep, dan suspensi
parenteral yang digunakan untuk terapi depot intramuskular
Stabilitas suspensi : ada hubungan ↑ derajat tiksotropi
maka laju sedimentasi akan menjadi lebih lambat.
Choice of Viscometer
1. Newtonian systems: 2. Non-Newtonian systems:
Dalam sistem Newton karena The instrumentation used must
laju geser berbanding lurus be able to operate at a variety
dengan tekanan geser, maka of rates of shear.
dapat digunakan instrumen yang Only by the use of “multi-point”
beroperasi pada laju geser instruments is it possible to
tunggal. obtain the complete rheogram
Instrumen ini menghasilkan satu for these systems. Can be used
titik pada reogram, dengan with both Newtonian and non-
menarik garis melewati titik ini Newtonian systems.
ke titik nol akan menghasilkan Cup and bob & cone and plate
reogram yang lengkap. viscometers.
Viskometer kapiler &
viskometer bola jatuh biasa
digunakan pada bahan
Newtonian.
Viscosity Measurement
Capillary viscometer:
The viscosity of a Newtonian
liquid may be determined by
measuring the time required for
the liquid to pass between two
marks as it flows by gravity a
vertical capillary tube, known as a
Ostwald viscometer.
Viscosity Measurement
The time of flow of the liquid under test is compared with the
time required for a liquid of known viscosity (usually water,
i.e. 1.0019 cps) to pass between two marks.
If 1 and 2 are the viscosities of the unknown and the
standard liquids. 1 and 2 are the densities of the liquids,
and t1 and t2 are the respective flow times in seconds. The
absolute viscosity of the unknown liquid, 1, is determined
using the following equation:
1 1t1
2 2 t 2
The Hoeppler Viscometer
1) The sample and ball are Falling sphere Viscometer:
placed in the inner glass In this type of viscometer, a glass or steel
tube and allowed to ball rolls down an almost vertical glass
reach temperature tube containing the test liquid.
equilibrium with the
water in the
surroundings constant
temperature jacket.
2) The tube and jacket are
then inverted.
3) The time for the ball to
fall between two marks
is accurately measured
and repeated several
times.
Cup and bob viscometers:
The sample is sheared in the space
between the outer wall of a bob & the
inner wall of a cup into which the bob fits.
The various instrument available differ
mainly in whether the torque results from
rotation of the cup or of the bob
Couette type the cup is rotated, the resultant
torque is proportional to the viscosity of the sample
(exp: MacMichael viscometer)
Searle type stationary cup and a rotating bob,
the torque resulting from the viscous is generally
measured by a spring or sensor in the drive to the
bob (exp: rotovisco viscometer, stormer
viscometer)
Kelemahan: adanya aliran sumbat ruang pisah (gap) antara bob & cup
Cone and plate viscometer
(exp : Ferranti-Shirley viscometer)
Cara kerja : Tidak terpengaruh aliran sumbat
Sampel ditempatkan di tengah lempang diam, kemudian dinaikkan
posisinya sampai di bawah kerucut, kemudian kerucut dikemudikan
dengan kecepatan yang dapat diubah-ubah.
Viskositas dr cairan Newton dihitung dgn menggunakan persamaan :
= C (T/v)
Dimana :
C = konstanta alat; T = torque (puntiran)
yang terbaca; v = kec kerucut berputar
per menit
Viskositas plastis (U) = C ((T – Tf)/v)
Yield value (f) = Cf x Tf
Dimana :
Tf = torque (puntiran) pada sumbu
shearing stress; Cf = konstanta alat
Viskoelastik
Analysis of viscoelastic materials is design instead not to destroy
the structure can provide information on the intermoleculer
& interparticle forces in the material
Pengukuran viskoelastik berdasarkan atas sifat mekanis zat
(bahan) yang menunjukkan sifat kental (viscous) cairan dan sifat
kenyal (elastis) padatan.
Sistem dalam farmasi krim, losio, salep, supositoria, suspensi,
dan zat-zat pendispersi koloidal, peng-emulsi serta pensuspensi.
Evaluasi reologis dari semisolid viskoelastik creep test, yaitu
suatu tekanan tiba-tiba diberikan dan dipertahankan pada
periode waktu tertentu; dan uji osilasi (oscillatory testing),
melalui pengujian ini tidak terjadi gangguan struktur dari bahan
uji.
Factors affecting rheological properties
1. Chemical factors
A- Degree of polymerization
the longer polymer molecules may be susceptible to shear depolymerization will be
accompanied by decrease in viscosity as was found for sodium alginate.
B- Extent of Polymer Hydration
In hydrophilic polymer solution the molecules are regarded as completely
surrounded by immobilized water molecules forming a solvent layer. Such hydration
of hydrophilic polymers gives rise to an increased viscosity.
C- Impurities, Trace Ions and Electrolytes
Chemical impurities are the major factors in changing the viscosity of natural
polymers e.g. in Na alginate solution, the viscosity increase if traces of Ca are
present, due to the formation of calcium alginate.
D- Effect of pH
Changes in pH greatly affect the viscosity and stability of the hydrophilic natural and
synthetic gums. The natural gums usually have a relatively stable viscosity plateau
extending over 5 or 4 pH units. Above and below this pH range viscosity decreases
sharply.
2- Physical Factors
A- Temperature
A temperature increase usually produces a rapid viscosity decrease, with
the exception of certain synthetic polymers such as methyl cellulose,
B- Light
Various hydrocolloids in aqueous solutions are reported to be sensitive to
light. These colloids include carbopol, Na alginate, and Na CMC. To protect
photosensitive hydrocolloids from decomposition and resultant viscosity
change use light-resistant containers
Pharmaceutical & Biological Applications of
Rheology
(1) Prolongation of Drug Action
There is a great difference in the rate of absorption of an ordinary
suspension and the same when it is thixotropic. The suspension is shaken
before administration to be easily injected but in the body it becomes high
consistency leading to prolonged action.
(2) Effect on Drug Absorption
The viscosity of creams and lotions may affect the rate of absorption. A
greater release of active ingredients is generally possible from the softer,
less viscous bases.
(3) Thixotropy, Drug Stability & Suspension
Substances are susceptible to decomposition (vitamins) are found to be
stable for longer periods of time in thixotropic preparations, as such
substances are in a state of complete rest, in a solid gel. Suspension has
high viscosities to retard sedimentation and creaming. When it is desired
to pour some of the suspension or emulsion from its container, it is shaken
well.
