Академический Документы
Профессиональный Документы
Культура Документы
Rheology: has been derived from Greek words rheo to flow and logos science. Viscosity is an expression of the resistance of a fluid to flow. The higher the viscosity, the greater the resistance. Rheology may thus be defined as: The science concerned with the study of the deformation of matter under the influence of stress, which may be applied perpendicularly to the surface of a body (tensile stress) or tangentially to the surface of a body (a shearing stress) or at any other angle to the surface of the body.
Importance of Rheology:
Rheology is involved in the:
In preparation, development and evaluation of pharmaceutical dosage forms e.g., suspensions, emulsions, pastes, suppositories, tablets coating, ., etc. Mixing and Flow of materials Packaging into containers Removal prior to use
2) Non-Newtonian Systems They fail to follow Newtons law of flow. Examples: Colloidal Solutions, Emulsions, Liquid Suspensions, Gels and Ointments.
6
1. Newtonian systems
Newton's law of flow:
1. Let us consider a block of liquid consisting of parallel plates of molecules. 2. The bottom layer is considered to be fixed in place. 3. 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.
4. The velocity difference, dv, between two planes of liquid separated by distance, dr, is the rate of shear (G) = dv/dr. 5. The force per unit area required to cause flow (F'/A) is called the shearing stress (F). 6. the higher the viscosity of a liquid, the greater the force per unit area (shearing stress) required to produce a certain rate of shear. 7. Thus, the rate of shear is directly proportional to the shearing stress. F'/A dv/dr F'/A = dv/dr (1) where is a constant known as viscosity =F/G (2) The unit of viscosity is poise or dyne.sec.cm-2 .
Velocity ,V Force,F
Area , A
Thickness , X
Newtonian systems have constant viscosity where = F / G. When we plot a rheogram of G against F, then a straight line is obtained passing through the origin, the slope of which is equal to the reciprocal of viscosity, a value referred to as the fluidity , =1/ Newtonian systems like water, simple organic liquids, true solutions and dilute suspensions and emulsions. Rheogram of a Newtonian liquid
Shear rate (G)
Slope = = 1 /
The passage through the origin indicates that even a mild force can induce flow in these systems.
The linear nature of the curve shows that the viscosity () of a newtonian liquid is a constant unaffected by the value of the rate of shear. Thus a single determination of viscosity from the shear stress at any given shear rate is sufficient to characterize the flow properties of a Newtonian liquid.
Kinematic Viscosity (S): The kinematic viscosity of a liquid is its absolute viscosity divided by the density at a definite temperature. kinematic viscosity (s) = / The units of kinematic viscosity are the stoke (s) and the centistoke (cs).
Relative Viscosity (r): It is the ratio of solution viscosity () to the viscosity of the solvent (o ) (in pharmaceutical products it is often water).
1. Plastic Flow:
Such materials are called Bingham bodies
The curve is linear over most of its length corresponding to that of a Newtonian fluid. However, the curve does not pass through the origin but rather intersects 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 or Bingham Yield value.
Contrary to a Newtonian liquid that flows under the slightest force, a Bingham body does not flow until a definite shearing stress equal to the yield value is applied. Below the yield value the system acts as an elastic material. Plastic systems resembles Newtonian systems at shear stresses above the yield value. The slope of the rheogram is termed mobility, analogous to fluidity in Newtonian systems and its reciprocal is known as the Plastic viscosity, U. U = (F - f) G
Plastic flow is associated with the presence of flocculated particles in concentrated suspensions, however ointments and creams are common examples for that system.
A yield value exists because of the contacts between adjacent particles (brought about by van der Waals forces), which must be broken down before flow can occur. Consequently, the yield value is an indication of force of flocculation: The more flocculated suspension, the higher will be the yield value. Plastic systems are shear-thinning systems
2. Pseudoplastic Flow:
A large number of pharmaceutical products, including natural and synthetic gums, e.g., liquid dispersions of tragacanth, sodium alginate, methyl cellulose, and Na CMC show 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 suspension
Curve for a pseudoplastic material begins at the origin consequently, in contrast to Bingham bodies, there is no yield value. Since no part of the curve is linear, one can not express the viscosity of a pseudoplastic material by any single value. The viscosity of a pseudoplastic substance decreases with increasing rate of shear (shear-thinning systems).
As the shearing stress is increased, the normally-disarranged molecules begin to align their long axes in the direction of flow.
Plastic Flow:
Pseudoplastic Flow:
Rheogram of a pseudoplastic material begins at the origin, there is no yield value. The viscosity of a pseudoplastic substance decreases with increasing rate of shear, why?
20
oNewtonian system is completely described by the viscosity. oPlastic system is described by the yield value and the plastic viscosity. oPseudoplastic systems which can not be described by a single value are expressed by: F N = G When N = 1, the flow is Newtonian As N rises the flow becomes increasingly non Newtonian. The term is a viscosity coefficient. The logarithmic form is a straight line equation log G = N log F log A straight line is obtained when log G is plotted against log F
3. Dilatant Flow:
Dilatant systems exhibit an increase in resistance to flow (viscosity) with increasing rates of shear, shear thickening systems. Such systems actually increase in volume when sheared and are hence termed dilatant. When the stress is removed, a dilatant system returns to its original state of fluidity.
Dilatant flow is the reverse of that possessed by pseudoplastic systems. Substances possessing dilatant flow properties are invariably suspensions containing a high concentration (about 50 percent or greater) of small, deflocculated particles. Particulate systems of this type which are flocculated would be expected to possess plastic, rather than dilatant flow characteristics.
Thus, one may pour a dilatant suspension from a bottle since under these conditions it is reasonably fluid.
As the shear stress is increased, the bulk of the system expands or dilates, hence the term dilatant. The particles, in an attempt to move quickly past each other, take on an open form of packing. Such an arrangement leads to a significant increase in the interparticle void volume.
The amount of vehicle remains constant and at some point, becomes insufficient to fill the increased voids between the particles. Accordingly, the resistance to flow increases because the particles are no longer completely wetted or lubricated by the vehicle.
Thus, the suspension will set up as a firm paste.
Closed packed particles minimum void volume sufficient vehicle low viscosity
open packed particles increase void volume insufficient vehicle high viscosity
26
Newtonian
Dilatant
Shear stress
Shear rate
Shear rate
Shear rate
Shear rate
How can characterize the following systems: Newtonian systems Non- Newtonian systems: a- plastic substance b- pseudoplastic substance c- dilatant
28
Thixotropy
Thixotropy is a property exhibited by certain gels (semisolid, jellylike colloids). A thixotropic gel appears to be solid and maintains a shape of its own until it is subjected to a shearing force or some other disturbance, such as shaking. It then acts as a sol (a semi-fluid colloid) and flows freely. If the rate of shear was increased and then was reduced once the desired maximum rate had been reached and plotted against the resultant shear stress, the downcurve would be identical with and superimposed on the up-curve in case of Newtonian systems.
29
The down curve for non-Newtonian systems (plastic and pseudoplastic) 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 upcurve. This indicates a breakdown of structure that does not reform immediately when the stress is reduced or removed.-------- Thixotropy Thixotropic behavior is reversible, and when allowed to stand undisturbed the sol slowly reverts to a gel. Common thixotropic gels include certain paints and printing inks. Ketchup and yoghurt displays thixotropic properties
30
So, Thixotropy as a term means to change by touch. It is usually referred to as isothermal gel-sol-gel transformation. It is characterized by a breakdown of structure with agitation and followed by the reformation of the rigid structure when the material is allowed to stand undisturbed for some time. The breakdown of the structure does not reform immediately when the stress is reduced or removed.
Negative Thixotropy
It is also called antithixotropy, which represents an increase rather than a decrease in consistency when the system is sheared (shear thickening). It results from an increased collision frequency of dispersed particles or polymer molecules in suspension, resulting in increased interparticle bonding with time. Negative Thixotropy differed than dilatancy
33
Dilatant system is deflocculated and contains more than 50% by volume of solid dispersed phase.
Antithixotropic system has low solids content (1 to 10%) and are flocculated. At rest it is sol.
34
35
Measurement of Thixotropy:
1- The most apparent characteristic of a thixotropic system is the hysteresis loop, formed by the up- and down-curves of the rheogram.
This area of hysteresis has been proposed as a measure of thixotropic breakdown; it may be obtained readily by means of a Planimeter.
2- Determine the structure breakdown of plastic bodies at constant shearing rate and different time. B = U1-U2/ (ln t2/t1) B= thixotropic coefficient, U1 and U2 are plastic viscosity of two down curves after shearing at a constant rate for t1 and t2 second. 3- Determine the viscosity due to increase shearing rate M = U1-U2/ (ln 2/ 1) M is the thixotropic coefficient, the rate of shear
36
Thixotropy in formulation
1- A well formulated thixotropic suspension will not settle out readily in the container, will become fluid on shaking, and will remain long enough for a dose to be dispersed. 2- Similar behavior is desired with emulsion, lotions, creams, ointments and parenteral suspension to be used as intramuscular depot therapy.
37
1- Capillary Viscometer:
Used for Newtonian system by determine the time
required for the liquid to pass between two marks as it flows by gravity through a vertical Capillary tube known as Ostwald Viscometer 1/ 2= t1/t2
V is the velocity of sedimentation of spherical particles, is the density of the spherical particles, o is the density of the medium, o is the viscosity of the medium and g is the acceleration due to gravity.
For description, the fluid is stationary in a vertical glass tube and a sphere of known size and density is allowed to descend through the liquid. The time for the ball to fall between two marks is accurately measured and repeated 40 several times .
41
where: t is the time in second for the ball to fall between two marks Sb , Sf are the specific gravity of the ball and the liquid B constant for particular ball N.B: Specific gravity is the ratio of the density (mass of a unit volume) of a substance to the density (mass of the same unit volume) of a reference substance
= t(Sb-Sf)B
42
44
The torque resulting from the viscous drag of the system under examination is generally measured by a spring or sensor in the drive to the bob. Stormer instrument should be used with systems having a viscosity below 20 cps.
= 1 T (1/R2b -1/R2c) 4h = (omega) T = torque in dyne cm h= depth to which the bob is immersed in the liquid R2b R2c are the radii of the cup and bob
45
The cone is driven by a variable speed motor and the sample is sheared
in the narrow gap between stationary plate and rotating cone. The rate of shear is controlled by a selector dial and the torque
cone
plate
46
For Plastic systems = C (T-Tf /) Tf is the torque at shearing stress axis (yield value)
47
Viscoelasticity:
The viscosity can be measured for both liquid and solid For liquid : = F/G the behavior expressed by flow properties of the liquid For solid: E= F/ E = elastic modules (dyne/cm) = the strain F = the stress (dyne/cm) the behavior expressed by elasticity properties of the solid
48
1.Temperature
A temperature increase usually produces a rapid viscosity decrease, with the exception of certain synthetic polymers such as methyl cellulose, whose aqueous solutions gel with temperature for a short period, due to hydration. Prolonged heating may produce drastic decrease in viscosity due to decomposition of the polymer, e.g., gelatin.
2. Aeration
Aerated products usually result from high shear milling. Aerated samples appear to be more viscous or have more viscous creamed layer than non-aerated samples. Some aerated emulsions will be less viscous and less stable than unaerated samples due to concentration of surfactant or emulsion stabilizer at the air-liquid interface and depletion of it at the oil-water interface.
mechanically by roll milling, which squeezes out the air or by heating the aerated system.
3. 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, antioxidants or in case of carbopol, the use of sequestering agents.
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 forms a compact, spherical deposits at the site of injection. These deposits resist disintegration by tissue fluids because of their high consistency which leading to prolonged or depot action as in case of procaine penicillin G. (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 and good Suspension Formulation Thixotropy is particularly useful in suspensions. These must be poured easily from containers, which requires low viscosity. It is possible to minimize or completely eliminate sedimentation and coagulation of insoluble particles to give a uniform dosage simply by agitation. (4)Thixotropy and Drug Stability Another useful aspect of thixotropy is that substances, which are susceptible to decomposition, such as 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.
(6) Effect on bioavailability: The rate of dissolution of a drug particle will be decreased as the viscosity of the dissolution medium is increased.
The use of hydrocolloids will exhibit non-newtonian behavior such as in case of griseofulvin in concentrations of methylcellulose, which will exhibit pseudoplastic behavior and delay absorption.
The absorption of drugs by the skin and from injection sites will be decreased by increase in the viscosity of the vehicle.
Thank you