Pharmaceutical Rheology: Fluid, Quasisolid, and Solid Material Behavior

What are the origins of the term "Rheology"?

From Greek: rheo (to flow) and logos (science)

Rheology

The study that describes flow of liquids & deformation of solids

What is involved in the study of Rheology?

- Fluids

- Quasisolids

- Solids

- Pharmaceutical Processing

Rheology is essential for understanding and controlling how pharmaceutical fluids are [...]

Processed, packaged and stabilized

Rheology of Fluids: What are two scales at which mixing of fluids occurs?

Small lab scale or manufcaturing scale

Rheology of Fluids: What process reduces particle size of disperse systems?

Particle size reduction with shear

Rheology of Fluids: What are examples of fluid passage through orifices?

- Pouring

- Packaging in bottles

- Passage through hypodermic needles

Rheology of Fluids: fluid transfer includes [...] & [...] through pipes

pumping & flow through pipes

Rheology of Fluids: What aspect of disperse systems' behavior should be MAINTAINED?

Physical stability

Rheology is essential for understanding how quasisolids/semisolids behave when [...]

Behave when spread, removed, mixed or released

Rheology of Quasisolids/Semisolids: What property of quasisolids/semisolids affects how they cover and stay on the skin?

Spreading and adherence on skin

Rheology of Quasisolids/Semisolids: How are quasisolids/semisolids removed?

Removal from jars or extrusion from tubes

Rheology of Quasisolids/Semisolids: What ability do quasisolids/semisolids have regarding liquids?

Capacity of solids to mix with miscible liquids

Rheology of Quasisolids/Semisolids: What process involves the drug moving out of the base in quasisolids/semisolids?

Release of drug from base

Rheology of Quasisolids/Semisolids: Why are quasisolids/semisolids important?

They are important in pharmaceutical compounding

Rheology is essential for understanding how solid materials [...] during tablet and capsule manufacturing

Flow, fill, and pack during tablet and capsule manufacturing

Rheology of Solids: What process involves the flow of powders in tableting machines or encapsulation?

Flow of powders from hoppers & into die cavities in tableting machines or into capsules during encapsulation

Rheology of Solids: What properties of solids affects how well they fill conatiners or dies?

Packagability of powdered or granular solids

How is Rheology essential for optimizing pharmaceutical processing?

- Ensuring production capacity of the equipment

- Processing efficiency

- Ensuring safety of operations

- Up-scaling from laboratory batches to production batches

Viscosity

An expression of the resistance of a fluid to flow (thickness)

The higher the resistance, the [...] the viscosity

The higher the resistance, the HIGHER the viscosity

Simple liquids have an [...] value of viscosity

Simple liquids have an ABSOLUTE value of viscosity

How are Complex systems' viscosity different from Simple liquid viscosity?

Complex systems viscosity CANNOT be expressed by a single value

Charcateristics of Rheology?

- Study of mixing & flow of materials

- Involves evaluation of effects of viscosity

What are the 2 types of systems in Rheology?

- Newtonian systems

- Non-Newtonian systems

Rheology class depends what?

Ddepends on whether flow properties are in accord with Newton's law of flow

Newtonian flow: In Newtonian flow, what is the velocity gradient or rate of shear represented by?

G

Newtonian flow: In Newtonian flow, how is rate of shear (G) defined?

*dv/dr

> dv = Rate of movement or velocity

Newtonian flow: In Newtonian flow, how is liquid described (*the graph)?

Described as a "block" consisting of parallel plates of molecules (like a deck of cards)

Newtonian flow: In Newtonian flow, what happens to the bottom and top planes of the liquid?

- The bottom plane is fixed

- The top plane is moved at constant velocity

Newtonian flow: In the visual representation of Newtonian flow, shearing force is required to produce a [...] gradient between the parallel planes of the a block of material

Shearing force is required to produce a definite velocity gradient between the parallel planes of the a block of material

Newtonian flow: In Newtonian flow, what is shear stress represented by?

F (force)

Newtonian flow: How is shear stress (F) related to area and velocity gradient?

* F= F'/A, which is proportional to dv/dr

> F' = shearing force applied to the top layer of the liquid

> A= area of the layer

Newtonian flow: What is the constant of proportionality in Newtonian flow?

n (eta)

Newtonian flow: What is the equation for Newtonian Flow?

F = nG

Newtonian flow: What is the equation for coefficient of viscosity?

VISCOSITY = F/G

Newtonian flow: What is the description of the rheogram (plot of F vs. G) for Newtonian flow?

- Straight line

- Indicates a constant velocity

- Viscosity doesn't change

Newtonian flow: In Newtonian flow, what does the slope of the rheogram represent?

FLUIDITY= o(phi)

Newtonian flow: What is FLUIDITY in relation to viscosity?

It is the reciprocal of viscosity

Newtonian flow: What is the equation relating fluidity and viscosity?

o = 1/n

Newtonian flow: What are examples of Newtonian fluids in pharmacy?

Water, glycerin 93%, castor oil, ethyl alcohol, etc.

What are the Units of Viscosity?

Units= poises or centipoises (cps)

What does poises or centipoises (cps) represent?

This is the shearing force required to give velocity of 1 cm/sec with an area of 1 cm2 and distance between two parallel planes of liquid 1cm apart

CGS units

Would be dyne sec cm^-2 or gram cm^-1 sec^-1 where 1 dyne = gram cm sec^-2

What is the USP units of Viscosity?

Units: Stokes (s) or centistokes (cs)

What is Kinematic viscosity?

Absolute viscosity/density

What is the MOST common in pharmaceutical systems, Newtonian flow or Non-Newtonian flow?

Non-Newtonian flow

Non-Newtonian flow: Simple Plastic flow

- More common in pharmaceutical systems than Newtonian

- Materials known as Bingham Bodies

- Shows yield value (occurs ONLY in plastic flow)

Non-Newtonian flow: Simple Plastic flow examples in pharmacy includes WHAT?

Flocculated particles in a concentrated suspension

"Flocculation"

Produced agglomerates of suspended particles in liquid systems held together by weak electrostatic forces

Non-Newtonian flow: What is the description of the rheogram (plot of F vs. G) for Simple plastic flow?

- It shows that no flow occurs UNTIL a minimum shear stress (yield value) is reached

- After the yield value is reached, the flow becomes linear

Yield value

*Minimum shear stress needed to start flow in material

- yield value represented as line drawn back to x-axis

- Can be measured as f

- Occurs ONLY in plastic flow

What are the units of Yield value?

dynes cm^-2

Why must a yield value be reached before a plastic suspension can flow?

Because contacts (Van der Waals forces) between adjacent particles must be broken down before suspension can flow easily

Plastic Viscosity (U)

U = (F-f)/G

Non-Newtonian flow: In Simple Plastic flow, how does a material act at stresses BELOW yield value?

Material acts as an elastic material

Non-Newtonian flow: In Simple Plastic flow, what does the slope of the rheogram represent?

Mobility

Non-Newtonian flow: Simple Pseudoplastic flow

- Non-Newtonian flow

- Natural & synthetic gums, liquid dispersions of tragacanth, Na alginate, Na carboxymethyl cellulose (CMC)

- i.e. Polymers in solution

Non-Newtonian flow: What is the description of the rheogram (plot of F vs. G) for Simple Pseudoplastic flow?

- NO part of rheogram is linear

- Shows a curved line starting from the origin, where the rate of shear INCREASES more rapidly than the shearing stress

(indicates that viscosity decreases with increasing shear [shear-thinning])

Viscosity DECREASES with [...] rates of shear

Viscosity DECREASES with INCREASING rates of shear

Simple Pseudoplastic Flow can ONLY calculate [...] VISCOSITY

APPARENT VISCOSITY

Non-Newtonian flow: Dilatant Flow

- Non-Newtonian flow

- System actually increases in volume when sheared

Non-Newtonian flow: In Dilatant Flow, Certain suspensions with high percentage of dispersed solids ( 50% + of small deflocculated particles) exhibit WHAT?

Exhibit INCREASE in resistance to flow with increasing rates of shear

Non-Newtonian flow: What is the description of the rheogram (plot of F vs. G) for Dilatant flow?

- It shows a curve that becomes flatter as shearing stress increases

- Means viscosity INCREASES with higher shear (indicating shear-thickening)

Dilatant behavior: Characteristics of Closely packed particles?

- Minimum void volume

- Sufficient vehicle

- Relatively low consistency

Dilatant behavior: Characteristics of Open packed (dilated) particles?

- INCREASED void volume

- Insufficient vehicle

- Relatively HIGH consistency

Shear-thinning systems

*Viscosity decreases with INCREASING Shear stress (F) or Rate of shear (G)

What would be an example of Shear-thinning?

Pseudoplastic

What would be an example of Shear-thickening?

Dilatant

Summary of equations

*F^N = eta /G

> When N = 1, flow is Newtonian

> When N less than 1, flow is dilatant

> When N greater than 1, flow is pseudoplastic

Linear equation: log G = N logF- log eta'

Relationship between temperature and viscosity: Viscosity of a liquid decreases when temperature is [...]

Viscosity of a liquid decreases when temperature is RAISED/INCREASED

Relationship between temperature and viscosity: Viscosity of a gas INCREASES with temperature. Therefore INCREASED viscosity of a gas = [...]

INCREASED viscosity of a gas = INCREASED temperature

Relationship between temperature and viscosity: Fluidity of a liquid (reciprocal of viscosity INCREASES with temperature. Therefore INCREASED fluidity of a liquid = [...]

INCREASED fluidity of a liquid = INCREASED temperature

Thixotropy

*"An isothermal & comparatively slow recovery, on standing of a material, of a consistency lost through shearing"

Characteristics of Thixotropy?

- Only in Non-Newtonian systems

- Usually shear thinning systems

What does Thixotropy indicate?

Indicates breakdown of structure (& hence shear thinning) that does not reform immediately when stress is removed or reduced

What kind of particles do thioxtropic systems usually contain?

Contain asymmetric particles that set up a loose three dimensional network throughout the sample

Describe Thixotrophy rheogram curves

- Down curve is displaced with regard to up curve

- Material has LOWER viscosity on down curve than on up curve

- Shows material has lower consistency at any one rate of shear on the down curve than it had on the up curve

What transformation occurs in thixotrophic materials when shear is applied to a gel?

A gel to sol transformation occurs and structure breaks down

How can Thixotropy be quantified?

Quantitated by measuring the area of hysteresis

Rheogram of thixotropic material with a bulge in the hysteresis loop: What do concentrated bentonite gels (10-15%) show on the rheogram?

show "bulge" in up curve

Rheogram of thixotropic material with a bulge in the hysteresis loop: What is the bulge in the curve caused by?

Caused by swelling of crystalline plates of bentonite within the 3D structure

Rheogram of the thixotropic material showing a spur value in the hysteresis loop: In still more highly structured systems, such as procaine penicillin gel formulation for IM injection. Results in WHAT effect?

results in drug depot effect

Rheogram of the thixotropic material showing a spur value in the hysteresis loop: Bulge in rheogram is large and is called a WHAT?

Spur

Rheogram of the thixotropic material showing a spur value in the hysteresis loop: SPUR VALUE (high yield)

Value that represents a sharp point of structural breakdown at low shear rates

What equipment determines rheological properties?

Viscometers

Determination of rheological properties (use of viscometers): Single shear rate viscometers

Viscometers that can only be used for Newtonian systems

Determination of rheological properties (use of viscometers): Variable shear rate viscometers

Viscometers that can be used for Newtonian & Non-Newtonian systems

Determination of rheological properties (use of viscometers): Ostwald Cannon-Fenske Viscometer

- Known also as a capillary viscometer

- Need reference material for which the absolute viscosity is known

- Measure time for reference material & then test material

What is the equation for the Ostwald Cannon-Fenske Viscometer?

Equation: n1 / n2 = p1 t1 / p2 t2 = relative viscosity of liquid under test

Determination of rheological properties (use of viscometers): Hoeppler Viscometer

- ONLY for Newtonian systems

- Known also as the Falling Ball or Falling sphere viscometer

- Water in the outside jacket, which maintains the temperature

What is the equation for the Hoeppler Viscometer?

*Equation: n = t (Sb - Sf ) B

- Sb is the specific gravity of the ball

- Sf is the specific gravity of fluid

- B is the instrument constant

- t = time for the ball to fall between two points

Determination of rheological properties (use of viscometers): Rotational cup and bob Viscometer

- Can be used for BOTH Newtonian and Non-Newtonian systems

What is an example of a Rotational cup and bob viscometer?

Couette viscometer, where the cup rotates

What type of viscometer has a stationary cup and a rotating bob?

Searle viscometer

Determination of rheological properties (use of viscometers): Cone plate viscometer

Cone spins & rate of shear in revs/min & viscous traction or torque (shearing stress) produced on the cone is read on the indicator scale

What is an example of a Cone plate viscometer?

Ferranti-Shirley viscometer

What is the equation for the Cone plate viscometer?

*Equation: n = C. T/ v = apparent viscosity inpoises

- C is the instrument constant

- T = torque

- v = revs/min(upsilon)

Viscoelasticity & Semisolids

*Viscoelastic properties observed in semisolids.

- A combination of liquid properties and those of a solid.

What viscometer is Viscoelasticity and Semisolids measured by?

Creep viscometer (plot a creep curve)