RHEOLOGYRHEOLOGY

DefinitionDefinition::

The branch of physics, which deals with deformation The branch of physics, which deals with deformation and flow of matter. and flow of matter.

Rheology governs the circulation of blood & lymph Rheology governs the circulation of blood & lymph through capillaries and large vessels, flow of mucus, through capillaries and large vessels, flow of mucus, bending of bones, stretching of cartilage, contraction bending of bones, stretching of cartilage, contraction of muscles.of muscles.

Fluidity of solutions to be injected with hypodermic Fluidity of solutions to be injected with hypodermic syringes or infused intravenously, flexibility of syringes or infused intravenously, flexibility of tubing used in catheters, extensibility of gut.tubing used in catheters, extensibility of gut.

From the rheological viewpoint From the rheological viewpoint systems are: systems are:

Solid if they preserve shape & volume. Solid if they preserve shape & volume. Liquid if they preserve their volume. Liquid if they preserve their volume. Gaseous if neither shape nor volume Gaseous if neither shape nor volume

remains constant when forces are remains constant when forces are applied to them. applied to them.

To the pharmacist:To the pharmacist: Flow of emulsions through colloid mills, Flow of emulsions through colloid mills, Working of ointments on slabs or roller Working of ointments on slabs or roller

mills.mills. Trituration of suspensions in mortar and Trituration of suspensions in mortar and

pestle.pestle. Mechanical properties of glass or plastic Mechanical properties of glass or plastic

containers & of rubber closures. containers & of rubber closures.

To the consumer:To the consumer: Squeezing toothpaste from a collapsible Squeezing toothpaste from a collapsible

tube. tube. Spreading lotion on his skin. Spreading lotion on his skin. Spraying liquids from atomizers or aerosol Spraying liquids from atomizers or aerosol

cans. cans.

Types of FlowTypes of Flow::

The choice depends on whether or The choice depends on whether or not their flow properties are in not their flow properties are in accordance to Newton's law of flow.accordance to Newton's law of flow.

Newtonian Non - Newtonian

Representation of flow of liquid

Newton Law of Flow:Newton Law of Flow: LaminarLaminar or or Stream lineStream line: : The bottom layer The bottom layer

is considered to be fixed in place. If the top plane of is considered to be fixed in place. If the top plane of liquid is moved at a constant velocity, each lower liquid is moved at a constant velocity, each lower layer will move with a velocity layer will move with a velocity ∞∞ to its distance to its distance from the stationary layer.from the stationary layer.

Velocity gradientVelocity gradient or or rate of shear rate of shear , , dv / drdv / dr. . The rate of shear indicates how fast the liquid flows The rate of shear indicates how fast the liquid flows

when a shear stress is applied to it. Its unit is secwhen a shear stress is applied to it. Its unit is sec -1-1. . The force per unit area (The force per unit area (F'/A)F'/A) required to bring about required to bring about

flow is called the shearing stress and its unit is flow is called the shearing stress and its unit is dyne/cmdyne/cm22. .

F'/A = η dv / dr (1)

Where η is the viscosity. Equation (1) is frequently written as: η = F/G (2)

Where F = F'/A & G = dv/dr.

For Newtonian System is shown in the figure. A straight line passing through the origin is obtained.

Units of Absolute Viscosity: The Poise (p), is the shearing force required to produce a velocity of 1 cm/sec. between two parallel planes of liquid each 1 cm2 in area & separated by a distance of 1 cm.

The Centipois (cp), 1 cp = 0.01 poise. Fluidity () is the reciprocal of viscosity:

() = 1/η (3)

Kinematic viscosity : is the absolute viscosity divided by the density of the liquid Kinematic viscosity = η/ρ (4)

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

Effect of Temperature on 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.

Non-Newtonian SystemsNon-Newtonian Systems::

Non - Newtonian bodies are those substances, Non - Newtonian bodies are those substances, which fail to follow Newton's law i.e. liquid & which fail to follow Newton's law i.e. liquid & solid , heterogeneous dispersions such as colloidal solid , heterogeneous dispersions such as colloidal solutions, emulsions, liquid suspensions and solutions, emulsions, liquid suspensions and ointments. ointments.

They are classified into 3 types of flow:They are classified into 3 types of flow: Plastic. Plastic. Pseudoplastic. Pseudoplastic. Dilatant.Dilatant.

Plastic FlowPlastic Flow::Materials exhibiting plastic flow are known as Materials exhibiting plastic flow are known as Bingham bodiesBingham bodies..

The plastic flow curve does The plastic flow curve does not pass through the origin not pass through the origin & it intersects the shearing & it intersects the shearing stress axis (or will if the stress axis (or will if the straight part of the curve is straight part of the curve is extrapolated to the axis) at a extrapolated to the axis) at a particular point referred to particular point referred to as as yield valueyield value.. (f)

A Bingham body does not A Bingham body does not begin to flow until a begin to flow until a shearing stress, shearing stress, corresponding to the yield corresponding to the yield value, is exceeded.value, is exceeded.

The slope of the rheogramThe slope of the rheogram = = mobilitymobility, , ( ( fluidity influidity in

Newtonian systems).Newtonian systems).

Its reciprocal is known as theIts reciprocal is known as the plastic viscosityplastic viscosity . .

U = ( F-f ) / GU = ( F-f ) / G (5)(5)

where where f f is the yield value, or (intercept, on the shear is the yield value, or (intercept, on the shear

stress axis in dynes cmstress axis in dynes cm-2-2). ).

U is the plastic viscosity.U is the plastic viscosity.

Plastic flow is associated with the presence of flocculated particles Plastic flow is associated with the presence of flocculated particles in concentrated suspensions. in concentrated suspensions.

continuous structure is set up.continuous structure is set up.

The yield value is present due to contacts between adjacent particles The yield value is present due to contacts between adjacent particles (brought about by V(brought about by Van der Waal'san der Waal's forces). forces).

Consequently, the yield value is an indication of the force of Consequently, the yield value is an indication of the force of flocculation, the more flocculated the suspension, the higher will be flocculation, the more flocculated the suspension, the higher will be the yield value. the yield value.

Frictional forces between moving particles can also contribute to the Frictional forces between moving particles can also contribute to the yield value. yield value.

Once the yield value has been exceeded, any in shearing stress Once the yield value has been exceeded, any in shearing stress (i.e. (i.e. F-f F-f ) brings about a directly proportional increase in ) brings about a directly proportional increase in GG, the rate , the rate

of shear. of shear. Aplastic system resembles a Newtonian system at shearAplastic system resembles a Newtonian system at shear stresses > the yield value.stresses > the yield value.

Pseudoplastic FlowPseudoplastic Flow::Polymers in solution, natural & synthetic gums, e.g. liquid dispersions of tragacanth, sodium alginate, methylcellulose .

The curve for a pseudoplastic material begins at the origin (or at least approaches it at low rates of shear). The curved rheogram The curved rheogram for pseudoplastic materials is due for pseudoplastic materials is due to shearing action on the long to shearing action on the long chain molecules of materials such chain molecules of materials such as linear polymersas 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.

FN = η' G (6)

The exponent N rises as the flow becomes increasingly non-Newtonian.

When N = 1, equation (6) reduces to equation (2) & the flow is Newtonian. F= η' GThe term η' is a viscosity coefficient.

Following rearrangement, equation (6) may be written in the logarithmic form:

log G = N log F - log η' (7) This is an equation for a straight line. Many pseudoplastic systems fit this equation when log G is plotted as a function of log F.

Shearing stress

Coiling & entanglement Alignment & disentanglement

Random & Brownian motion in fluids

Shear stress applied to the fluid

Due to

As the shearing stress the normally disarranged As the shearing stress the normally disarranged molecules begin to align their long axes in the molecules begin to align their long axes in the direction of flow. This orientation reduces the direction of flow. This orientation reduces the internal resistance of the material and allows a internal resistance of the material and allows a greater rate of shear at each successive shearing greater rate of shear at each successive shearing stress. stress.

In addition, some of the solvent associated with the In addition, some of the solvent associated with the molecules may be released, resulting in an effective molecules may be released, resulting in an effective lowering of the concentration and size of dispersed lowering of the concentration and size of dispersed molecules. molecules.

An equilibrium exists between the shear induced An equilibrium exists between the shear induced changes and random coiling tendency caused by changes and random coiling tendency caused by Brownian motionBrownian motion which entraps water inside the which entraps water inside the coils. The rate of entanglement and randomization by coils. The rate of entanglement and randomization by Brownian motionBrownian motion is constant, while the rate of is constant, while the rate of disentanglement and alignment increases with disentanglement and alignment increases with increasing shear stress. increasing shear stress.

The viscosity diminishes as the shear is increased, The viscosity diminishes as the shear is increased, so they known as so they known as ““shear thinning systemsshear thinning systems””..

FN = η' G (6)

The exponent N rises as the flow becomes increasingly non-Newtonian.

When N = 1, equation (6) reduces to equation (2) and the flow is Newtonian. The term η' is a viscosity coefficient.

Following rearrangement, equation (6) may be written in the logarithmic form:

log G = N log F - log η' (7)

This is an equation for a straight line. Many pseudoplastic systems fit this equation when log G is plotted as a function of log F.

Dilatant FlowDilatant Flow::

Certain suspensions with a Certain suspensions with a high percentage of high percentage of dispersed solids exhibit an dispersed solids exhibit an in resistance to flow with in resistance to flow with increasing rates of shear. increasing rates of shear.

Such systems actually Such systems actually increase in volume when increase in volume when sheared & are called sheared & are called dilatant. dilatant.

Dilatant materials "shear Dilatant materials "shear thickening systems." thickening systems."

When the stress is removed, When the stress is removed, a dilatant system returns to a dilatant system returns to its original state of fluidity.its original state of fluidity.

FN = η' G (6)

N is always < 1 and decreases as the degree of dilatancy increases.

As N approaches 1, the system becomes

increasingly Newtonian in behavior. Substances possessing dilatant flow

properties are invariably suspensions containing a high concentration (about 50 % or greater) of small, deflocculated particles.

At rest:Particles are closely packed with small interparticle volume. The amount of vehicle in the suspension is enough to fill this volume. The particles move

relative to one another at low rates of shear.

Applying shear stressParticle ,s arrangement is expanded, particles take an open formof packing (dilate). The amount of vehicle in the suspension is constant & becomes insufficient to fill the inter-particles voids .

The resistance to flow increases, the particles are no longer completely wetted or lubricated by the vehicle .Eventually, the suspension will set up as a firm paste.

Time-Dependent Behaviour:Time-Dependent Behaviour:ThixotropyThixotropy::

Newtonian systemsNewtonian systems: If the rate of shear was : If the rate of shear was reduced once the desired maximum rate had reduced once the desired maximum rate had been reached, the down curve would be been reached, the down curve would be identical with & superimposed on the up-curve. identical with & superimposed on the up-curve.

Non Newtonian systemsNon Newtonian systems:: With shear-thinning systems (i.e., plastic & With shear-thinning systems (i.e., plastic &

pseudoplastic), the down - curve is frequently pseudoplastic), the down - curve is frequently displaced to the left of the up-curve. This means displaced to the left of the up-curve. This means that the material has a lower consistency at any that the material has a lower consistency at any one rate of shear on the down-curve than it had one rate of shear on the down-curve than it had on the up curve. on the up curve. This phenomenon is known as Thixotropy.

Definition:It is a comparatively slow recovery, on standing of a material which lost its consistency through shearing."

Thixotropy is only applied to shear-thinning systems. This indicates a breakdown of structure (shear-thinning), which does not reform immediately when the stress is removed or reduced .

Gel structure

Asymmetric particles, many points of contact, network structure & rigid structure.

Sol structureBreakdown of structure, flow starts, particles are

aligned and transform to sol (shear thinning)

Removal of Shearing stress

Shearing stress

Gel structureRebuild of the gel structure by brownian motion

)time is not defined(

An aqueous dispersion of An aqueous dispersion of 8% w /w sodium bentonite8% w /w sodium bentonite sets to gel within an hour or two after preparation when sets to gel within an hour or two after preparation when undisturbed, but flows & can be poured within many undisturbed, but flows & can be poured within many minutes after it had been stirred above the yield value. minutes after it had been stirred above the yield value. After prolonged rest it reverts to a gel. After prolonged rest it reverts to a gel.

Thixotropic systems usually contain asymmetric particles Thixotropic systems usually contain asymmetric particles which, possess numerous points of contact & set up a which, possess numerous points of contact & set up a loose three-dimensional network. loose three-dimensional network.

At restAt rest, this structure confers some, this structure confers some degree of rigidity on degree of rigidity on the system & it resembles a gel.the system & it resembles a gel.

As shear is applied & flow starts, this structure begins to As shear is applied & flow starts, this structure begins to break down. Points of contact are disrupted & the break down. Points of contact are disrupted & the particles become aligned. particles become aligned.

The material a gel-to-sol transformation & The material a gel-to-sol transformation & exhibits shear thinning. exhibits shear thinning.

Upon removal of the stress, the structure starts to Upon removal of the stress, the structure starts to reform. This process is not immediate. It is a progressive reform. This process is not immediate. It is a progressive restoration of consistency as the asymmetric particles restoration of consistency as the asymmetric particles come into contact with each other by undergoing random come into contact with each other by undergoing random brownian movement. brownian movement.

The rheograms obtained with thixotropic materials are The rheograms obtained with thixotropic materials are dependent on:dependent on:

1- The rate at which shear is increased or decreased.1- The rate at which shear is increased or decreased. 2- The time for which a sample is subjected to any one 2- The time for which a sample is subjected to any one rate of shear.rate of shear.

Choice of ViscometerChoice of Viscometer

““One point" instruments :One point" instruments : provide a single point on the rheogram. provide a single point on the rheogram. Extrapolation of a line through this Extrapolation of a line through this

point to the origin will result in the point to the origin will result in the complete rheogram. complete rheogram.

Used for Newtonian fluids. Since the Used for Newtonian fluids. Since the rate of shear is directly proportional to rate of shear is directly proportional to the shearing stress.the shearing stress.

The capillary and falling sphere are for use only with The capillary and falling sphere are for use only with Newtonian materials Newtonian materials

“ “Multi-point" instruments:Multi-point" instruments: Used with non-Newtonian systems Used with non-Newtonian systems The instrumentation used must be The instrumentation used must be

able to operate at a variety of rates able to operate at a variety of rates of shear. of shear.

Cup and Bob , Cone and Plate Cup and Bob , Cone and Plate viscometers may be used with both viscometers may be used with both types of flow system types of flow system

::Falling Sphere ViscometerFalling Sphere ViscometerThe sample & ball are placed in the inner glass tube & allowed to reach temperature equilibrium with the water in the surrounding constant temperature jacket .

The tube & jacket are then inverted, which effectively places the ball at the top of the inner glass tube .

The time for the ball to fall between two marks is accurately measured & repeated several times .

For newtonian liquids:

B ( Sb – Sf ) η = t

tt = the time interval in sec. = the time interval in sec. Sb Sb & & SfSf are the specific gravities of are the specific gravities of

the ball & fluid under examination at the ball & fluid under examination at the temperature being used. the temperature being used.

BB is a constant for a particular ball is a constant for a particular ball and is supplied by the manufacturer. and is supplied by the manufacturer.

The instrument can be used over the The instrument can be used over the range 0.5 to 200,000 poise. range 0.5 to 200,000 poise.

::Cone and Plate ViscometerCone and Plate Viscometer

The sample is placed at the center of the plate The sample is placed at the center of the plate which is then raised into position under the conewhich is then raised into position under the cone..

The cone is driven by a variable speed motor & the The cone is driven by a variable speed motor & the sample is sheared in the narrow gap between the sample is sheared in the narrow gap between the stationary plate and the rotating conestationary plate and the rotating cone..

The rate of shear in rev. /min. is increased & The rate of shear in rev. /min. is increased & decreased by a selector dial & the torque decreased by a selector dial & the torque (shearing stress) produced on the cone is read on (shearing stress) produced on the cone is read on the indicator scalethe indicator scale..

A plot of rpm or rate of shear versus scale reading A plot of rpm or rate of shear versus scale reading or shearing stress may be plottedor shearing stress may be plotted..

C is an instrumental constant .

T is torque reading.

V is speed in revolution / minute.

C T / V = η

U = C (T - T f ) / V

f = T f x C f C f is constant

Plastic materials

The rate of shear is constant throughout the The rate of shear is constant throughout the entire sample being sheared. As a result, any entire sample being sheared. As a result, any change in plug flow is avoided. change in plug flow is avoided.

Time saved in cleaning & filling.Time saved in cleaning & filling. Temperature stabilization of the sample Temperature stabilization of the sample

during a run. during a run. The cone and plate viscometer requires a The cone and plate viscometer requires a

sample volume of 0.l to 0.2 ml. This sample volume of 0.l to 0.2 ml. This instrument could be used for the rheological instrument could be used for the rheological evaluation of some pharmaceutical semisolids.evaluation of some pharmaceutical semisolids.

AdvantagesAdvantages: :

Factors Affecting Rheological Factors Affecting Rheological Properties inProperties in Pharmaceutical Pharmaceutical ProductsProducts::

Chemical Factors:Chemical Factors:(a) Degree of Polymerization:(a) Degree of Polymerization: Suspending agents, and emulsion Suspending agents, and emulsion

stabilizers act in low concentrations to stabilizers act in low concentrations to produce viscous solutions (high produce viscous solutions (high molecular weight). molecular weight).

Lower concentrations of the high Lower concentrations of the high molecular weight grades of synthetic molecular weight grades of synthetic & modified natural gums are used to & modified natural gums are used to obtain the desired viscosity. obtain the desired viscosity.

(b) Extent of Polymer Hydration:(b) Extent of Polymer Hydration: In hydrophilic polymer solution the In hydrophilic polymer solution the

molecules are completely surrounded by molecules are completely surrounded by immobilized water molecules forming a immobilized water molecules forming a solvent layer. Such hydration of hydrophilic solvent layer. Such hydration of hydrophilic polymers gives rise to an increased viscosity.polymers gives rise to an increased viscosity.

The solvate layer is strongly bound to the The solvate layer is strongly bound to the macromolecule viscosity will be macromolecule viscosity will be insensitive to pH changes or low insensitive to pH changes or low concentrations of electrolytes. concentrations of electrolytes.

Loose solvate around the macromolecules, Loose solvate around the macromolecules, pH & electrolytes will produce variations pH & electrolytes will produce variations in viscosity.in viscosity.

))cc ( (Impurities, Trace Ions and ElectrolytesImpurities, Trace Ions and Electrolytes Changing the viscosity of natural polymers, e.g. in

sodium alginate solution, the viscosity to the gelling point traces of calcium are present the formation of calcium alginate.

At concentrations, electrolytes do not change the At concentrations, electrolytes do not change the viscosity of natural colloids in aqueous solution. viscosity of natural colloids in aqueous solution.

concentrations, the salts compete for the adsorbed concentrations, the salts compete for the adsorbed water molecules, surrounding the hydrated polymer, water molecules, surrounding the hydrated polymer, due to the affinity of the salt ions for water. due to the affinity of the salt ions for water.

As the polymer molecules become dehydrated, their As the polymer molecules become dehydrated, their dispersions decrease in viscosity & precipitationdispersions decrease in viscosity & precipitation occurs occurs

))d) Effect of pHd) Effect of pH::

Changes in pH greatly affect the viscosity & stability of Changes in pH greatly affect the viscosity & stability of the hydrophilic natural & synthetic gums. the hydrophilic natural & synthetic gums.

The natural gums usually have a relatively stable The natural gums usually have a relatively stable viscosity plateau extending over 5 or 4 pH units. Above viscosity plateau extending over 5 or 4 pH units. Above and below this stable pH range viscosity decreases and below this stable pH range viscosity decreases sharply. sharply.

Methyl cellulose has a stable pH range of 3 to 12. Methyl cellulose has a stable pH range of 3 to 12.

Sodium salts polymers are unstable in acid medium due Sodium salts polymers are unstable in acid medium due to the separation of the acid form of the polymer, e.g. to the separation of the acid form of the polymer, e.g. sodium alginatesodium alginate..

(E) Sequestering Agents and Buffers:(E) Sequestering Agents and Buffers: Sequestering agents have a stabilizing effect on viscosity in Sequestering agents have a stabilizing effect on viscosity in

some polymer solutions, which are decomposed by traces of some polymer solutions, which are decomposed by traces of metals.metals.

ExamplesExamples:: Calcium ions the viscosity of sodium alginate. Addition ofCalcium ions the viscosity of sodium alginate. Addition of sequestering agents i.e. EDTA or hexameta-phosphate will sequestering agents i.e. EDTA or hexameta-phosphate will viscosity in sodium alginate solutions. viscosity in sodium alginate solutions.

Tragacanth solution also suffers a rapid loss in viscosity, Tragacanth solution also suffers a rapid loss in viscosity, regardless of the pH, in systems, which bind calcium ions,regardless of the pH, in systems, which bind calcium ions, i.e citrate buffers. i.e citrate buffers.

Physical Factors:Physical Factors:(a) (a) Aeration:Aeration:

Aerated products usually result from high shear milling. Aerated products usually result from high shear milling. Aerated samples are more viscous or have more viscous Aerated samples are more viscous or have more viscous creamed layer than non-aerated samples. creamed layer than non-aerated samples.

Some aerated emulsions will be less viscous & less stable Some aerated emulsions will be less viscous & less stable than un-aerated samples due to concentration of the than un-aerated samples due to concentration of the surfactant or emulsion stabilizer at the air liquid interface & surfactant or emulsion stabilizer at the air liquid interface & thus deletion of the stabilizer at the oil - water interface. thus deletion of the stabilizer at the oil - water interface.

De-aeration is done: Mechanically by roll milling, which squeezes out the air. Mechanically by roll milling, which squeezes out the air. Heat the aerated system.Heat the aerated system.

(b) Light:(b) Light: Various hydrocolloids in aqueous solutions Various hydrocolloids in aqueous solutions

are reported to be sensitive to light. These are reported to be sensitive to light. These colloids include carbopol, sodium alginate colloids include carbopol, sodium alginate & sodium carboxymethyl cellulose. & sodium carboxymethyl cellulose.

To protect photosensitive hydrocolloids To protect photosensitive hydrocolloids from decomposition:from decomposition:

The use of light-resistant containers, The use of light-resistant containers, Screening agents, antioxidants.Screening agents, antioxidants. In the case of carbopol, the use of In the case of carbopol, the use of

sequestering sequestering

agents.agents.

(c) The Degree of Dispersion and (c) The Degree of Dispersion and Flocculation Flocculation:: In concentrated suspensionsIn concentrated suspensions of of 3% solids & 3% solids &

higherhigher, , a decrease in particle size of the solid phase, a decrease in particle size of the solid phase, produce an increase in the viscosity of the system. produce an increase in the viscosity of the system.

This viscosity increase to immobilization of the This viscosity increase to immobilization of the vehicle with an increase in the fraction of the vehicle with an increase in the fraction of the suspension volume effectively occupied by the solid. suspension volume effectively occupied by the solid.

The addition of insoluble solids to a Newtonian vehicleThe addition of insoluble solids to a Newtonian vehicle non-Newtonian flow properties in system. non-Newtonian flow properties in system. The smaller the particle size of the dispersed solid phase, The smaller the particle size of the dispersed solid phase,

the lower the concentration of the solids required to the lower the concentration of the solids required to produce non-newtonian flow and thixotropy.produce non-newtonian flow and thixotropy.

FlocculationFlocculation of a suspension system: of a suspension system:

Flocculation viscosity & thixotropy. Flocculation viscosity & thixotropy.

The flocs or aggregates are held weakly together and The flocs or aggregates are held weakly together and are capable of forming extended networks which give are capable of forming extended networks which give the flocculated suspension its structural properties. the flocculated suspension its structural properties.

Immobilization of a portion of the dispersing media Immobilization of a portion of the dispersing media in the network & between the flocs viscosity.in the network & between the flocs viscosity.

Pharmaceutical and Biological Pharmaceutical and Biological Applications of RheologyApplications of Rheology::

1- Prolongation of Drug Action:1- Prolongation of Drug Action: The rate of absorption of an The rate of absorption of an

ordinary suspension differs from ordinary suspension differs from thixotropic suspensionthixotropic suspension..

Example:Example: procaine penicillin G, a form of procaine penicillin G, a form of penicillin, of relatively low water solubility. penicillin, of relatively low water solubility. Aqueous suspensions containing between 40 and Aqueous suspensions containing between 40 and 70% w/v of milled or micronized procaine 70% w/v of milled or micronized procaine penicillin G + small amount of sodium citrate & penicillin G + small amount of sodium citrate & polysorbate 80 are thixotropic pastes & are of depot polysorbate 80 are thixotropic pastes & are of depot effect when injected intramuscularlyeffect when injected intramuscularly ..

Ordinary suspension of pencillin G

Thixotropy suspension of pencillin G

I.M injection

Forms no depot, fast dispersion & absorption so maintain therapeutic

Level for short time

Forms spherical deposits at site of injection which resists disintegration

by tissue fluids& Small surface area ) absorption (so maintain therapeutic

Level for longer time The formation of depot depends on: a- high yield value

b-fast thixotropic recovery after injection.

(2)(2) Effect on Drug Absorption:Effect on Drug Absorption:

The viscosity of creams and lotions The viscosity of creams and lotions may affect the rate of absorption of may affect the rate of absorption of the products by the skin. the products by the skin.

A greater release of active A greater release of active ingredients is generally possible ingredients is generally possible from the softer, less viscous bases. from the softer, less viscous bases.

The viscosity of semi-solid products The viscosity of semi-solid products may affect absorption of these may affect absorption of these topical products due to the effect of topical products due to the effect of viscosity on the rate of diffusion of viscosity on the rate of diffusion of the active ingredients.the active ingredients.

(3) Thixotropy in Suspension and (3) Thixotropy in Suspension and EmulsionEmulsion Formulation: Formulation: Thixotropy is useful in the formulation of Thixotropy is useful in the formulation of

pharmaceutical suspensions and emulsions. They pharmaceutical suspensions and emulsions. They must be poured easily from containers (low viscosity) must be poured easily from containers (low viscosity)

Disadvantages of Low viscosity:Disadvantages of Low viscosity: Rapid settling of solid particles in suspensions and Rapid settling of solid particles in suspensions and

rapid creaming of emulsions. rapid creaming of emulsions. Solid particles, which have settled out stick Solid particles, which have settled out stick

together, producing sediment difficult to together, producing sediment difficult to redisperse ("caking or claying"). redisperse ("caking or claying").

Creaming in emulsions is a first step towards Creaming in emulsions is a first step towards coalescence. (break down of emulsion)coalescence. (break down of emulsion)

A thixotropic agent such as sodium A thixotropic agent such as sodium bentonite magma, colloidal silicon bentonite magma, colloidal silicon dioxide, is incorporated into the dioxide, is incorporated into the suspensions or emulsions to confer a high suspensions or emulsions to confer a high apparent viscosity or even a yield value .apparent viscosity or even a yield value .

At restAt rest : : High viscosities retard sedimentation & High viscosities retard sedimentation &

creaming . creaming . Yield values prevent them altogether; Yield values prevent them altogether;

since there is no flow below the yield since there is no flow below the yield stress, the apparent viscosity at low shear stress, the apparent viscosity at low shear becomes infinite becomes infinite

Pouring the suspension or emulsion from its container: Shaking at shear stresses above the yield Shaking at shear stresses above the yield

value value The agitation breaks down the thixotropic The agitation breaks down the thixotropic

structure so reducing the yield value to structure so reducing the yield value to zero & lowering the apparent viscosity. zero & lowering the apparent viscosity. This facilitates pouring. This facilitates pouring.

Back on the shelf, the viscosity slowly Back on the shelf, the viscosity slowly increases again and the yield value is increases again and the yield value is restored as Brownian motion rebuilds the restored as Brownian motion rebuilds the house-of-cards structure of bentonite. house-of-cards structure of bentonite.