MEDICINAL CHEM &

CHEMICAL/PHARMA PROCESSES

LECTURE 3 DR ANN HOPPER

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 TODAYS LECTURE

• WHAT IS VISCOSITY
• WHAT IS RHEOLOGY
• EFFECTS OF SHEARING ON VISCOSITY: SHEAR THINNING, SHEAR
THICKENING, YIELD STRESS, THIXOTROPY
• MEASUREMENT OF VISCOSITY: GLASS CAPILLARY. DYNAMIC
• EXAMPLES OF VISCOSITY EFFECTS ON PRODUCTS.

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 VISCOSITY

• VISCOSITY IS A MEASURE OF A FLUID'S RESISTANCE TO FLOW.

• IT IS THE INTERNAL FRICTION OF A FLUID, CAUSED BY MOLECULAR
ATTRACTION, WHICH MAKES IT RESIST A TENDENCY TO FLOW.
• THIS RESISTANCE RESTRICTS MOVEMENT OF ANY SOLID OBJECT
THROUGH THE FLUID AND ALSO RESTRICTS MOVEMENT OF THE FLUID
ITSELF PAST STATIONARY OBJECTS.

Dr Ann Hopper 3
GUESS THE ORDER OF HIGHEST TO LOWEST
VISCOSITY

1. TOOTHPASTE
2. WATER, Guess the highest
Guess the lowest
3. COOKING OIL,
4. COUGH MIXTURE,
5. SHAMPOO OR BUBBLE BATH.

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 VISCOSITY
• VISCOSITY IS THE MEASURE OF THE INTERNAL
FRICTION OF A FLUID. THIS FRICTION
BECOMES APPARENT WHEN A LAYER OF FLUID
IS MADE TO MOVE IN RELATION TO ANOTHER
LAYER.

The greater the friction, the greater the amount of force required
to cause this movement.

Dr Ann Hopper 5
• SHEAR RATE HOW FAST THE FLUID IS PHYSICALLY MOVED OR
DISTRIBUTED, AS IN:
• 1. POURING,
• 2.SPREADING,

• 3 SPRAYING,
• 4. MIXING (WOODEN SPOON) ,
• PUT IN ORDER FROM LOW TO HIGH SHEAR RATE?

• HIGHLY VISCOUS FLUIDS, THEREFORE, REQUIRE MORE FORCE

TO MOVE THAN LESS VISCOUS MATERIALS.
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 VISCOSITY
• CAN BE MEASURED SIMPLY BY HOW FAST FLUID
FLOWS OFF A SPOON OR THROUGH A HOLE IN A
CUP.
Ford Cup.
• THE RESULT IS IN SECONDS.
• THE SHEAR RATE IS THE TIME FOR THE LAYERS TO
MOVE PAST EACH OTHER AND THE FORCE NEEDED TO
MAKE THE LAYERS MOVE IS ____________
• TO FIND OUT MORE DETAIL CAN BE VERY
SOPHISTICATED INSTRUMENTS THAT MEASURE STRESS,
STRAIN, YIELD POINT ETC.

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 VISCOSITY

X = DISTANCE BETWEEN TWO PLATES.

THE UPPER PLATE IS KEPT IN MOTION IN THE Y-DIRECTION AND THE LOWER
PLATE IS KEPT STATIONARY.
V = VELOCITY (SPEED) THE PLATE IS MOVING BY APPLYING A FORCE F TO THE
TOP PLATE IN THE Y-DIRECTION.
THE FORCE PER UNIT AREA REQUIRED TO MAINTAIN THE UPPER PLATE (OF
AREA A) IN MOTION IS GIVEN BY
𝐹𝐹 𝑉𝑉 𝑑𝑑𝑑𝑑
= 𝑋𝑋 OR IN DIFFERENTIAL FORM 𝜏𝜏 = −𝜂𝜂
𝐴𝐴 𝑑𝑑𝑥𝑥
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V IS VELOCITY; A IS THE AREA OF A PLATE; F IS THE
FORCE ; η (ETA) IS VISCOSITY.
• SHEAR RATE DESCRIBES THE SHEARING THAT THE FLUID
EXPERIENCED AND IS THE TIME TAKEN FOR THE LAYERS TO
MOVE BY A CERTAIN DISTANCE. ITS MEASURED IN
RECIPROCAL SECOND (S-1 ) AND GIVEN THE SYMBOL S. OR γ
• SHEAR STRESS IS THE FORCE NEEDED TO MAKE THESE
LAYERS FLOW MEASURED IN PASCALS (PA) IT WILL
NORMALLY HAVE THE SYMBOL τ (TAU).

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 𝐹𝐹 𝑉𝑉 𝑑𝑑𝑑𝑑
• = OR IN DIFFERENTIAL FORM 𝜏𝜏 = −𝜂𝜂
𝐴𝐴 𝑋𝑋 𝑑𝑑𝑥𝑥

• USING THESE SIMPLIFIED TERMS, VISCOSITY MAY BE

DEFINED MATHEMATICALLY BY THIS FORMULA:
τ SHEAR STRESS (PA)
𝜂𝜂 = VISCOSITY = ———— = ———————
S (γ) SHEAR RATE (S-1 )
• THIS IS KNOWN AS NEWTONS LAW OF FRICTION.
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• NEWTON ASSUMED THAT ALL MATERIALS HAVE, AT A GIVEN TEMPERATURE,
A VISCOSITY THAT IS INDEPENDENT OF THE SHEAR RATE. IN OTHER WORDS,
TWICE THE FORCE WOULD MOVE THE FLUID TWICE AS FAST. HE WASN’T
QUITE RIGHT.
• NEWTONIAN FLUIDS EXAMPLES ARE WATER & OILS. SOMETIMES CALLED
PURELY VISCOUS FLUIDS.

Dr Ann Hopper 11
 VISCOSITY

τ SHEAR STRESS (Pa)

𝜂𝜂 = VISCOSITY = ———— = ———————
S (γ) SHEAR RATE (S-1 )
THE SI UNIT OF MEASURE FOR VISCOSITY IS PASCAL SECOND. (Pa.s)
AN OLDER UNIT IS CENTIPOISE. 1 Pa.s = 1000 CPS.
1mPa.s = 1 CPS

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HOW DO WE DETERMINE VISCOSITY

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 RHEOLOGY
• RHEOLOGY IS THE STUDY OF THE FLOW OF MATERIALS THAT BEHAVE IN AN
INTERESTING OR UNUSUAL MANNER. OIL AND WATER FLOW IN FAMILIAR,
NORMAL WAYS, WHEREAS MAYONNAISE, PEANUT BUTTER, CHOCOLATE,
BREAD DOUGH, AND SILLY PUTTY FLOW IN COMPLEX AND UNUSUAL WAYS.
IN RHEOLOGY, WE STUDY THE FLOWS OF UNUSUAL MATERIALS.”

• “… ALL NORMAL OR NEWTONIAN FLUIDS (AIR, WATER, OIL, HONEY) FOLLOW

THE SAME SCIENTIFIC LAWS. ON THE OTHER HAND, THERE ARE ALSO FLUIDS
THAT DO NOT FOLLOW THE NEWTONIAN FLOW LAWS. THESE NON-
NEWTONIAN FLUIDS, FOR EXAMPLE MAYO, PAINT, MOLTEN PLASTICS, FOAMS,
CLAYS, AND MANY OTHER FLUIDS, BEHAVE IN A WIDE VARIETY OF WAYS. THE
SCIENCE OF STUDYING THESE TYPES OF UNUSUAL MATERIALS IS CALLED
RHEOLOGY”

• FAITH MORRISON, “THE NEWS AND INFORMATION PUBLICATION OF THE SOCIETY OF

Dr Ann Hopper 14
RHEOLOGY”, VOL 73(1) JAN 2004, PP 8-10
 EXAMPLES OF COMPLEX FLUIDS
• PHARMACEUTICALS
• GELS (CREAMS, PARTICLE PRECURSORS)
• EMULSIONS (CREAMS)
• AEROSOLS (NASAL SPRAYS)
• SUSPENSIONS (ANALGESIC ANTACID ORAL)
• FOODS
• EMULSIONS (MAYONNAISE, ICE CREAM)
• FOAMS (ICE CREAM, WHIPPED CREAM)
• SUSPENSIONS (MUSTARD, CHOCOLATE)
• GELS (CHEESE)
• BIOFLUIDS
• SUSPENSION (BLOOD)
• GEL (MUCIN)
• SOLUTIONS (SPITTLE)
• PERSONAL CARE PRODUCTS
• SUSPENSIONS (NAIL POLISH, FACE SCRUBS)
• SOLUTIONS/GELS (SHAMPOOS, CONDITIONERS)
• FOAMS (SHAVING CREAM)
• POLYMERS 15
 WORLD’S LONGEST RUNNING LABORATORY
EXPERIMENT – THE PITCH DROP EXPERIMENT

• PITCH – DERIVATIVE OF TAR

• @ROOM TEMPERATURE FEELS SOLID AND CAN BE SHATTERED WITH A
BLOW OF A HAMMER

• THIS EXPERIMENT SHOWS THAT IN FACT AT ROOM TEMPERATURE

PITCH IS A FLUID!

Dr. Aldo Acevedo - ERC SOPS 16

 WORLD’S LONGEST RUNNING LABORATORY
EXPERIMENT – THE PITCH DROP EXPERIMENT

• 1927 – PROF PARNELL IN UNIV. OF

QUEENSLAND AUSTRALIA HEATED A SAMPLE
OF PITCH AND POURED IT INTO A GLASS
FUNNEL WITH A SEALED STEM. THREE YEARS
WHERE ALLOWED FOR IT TO SETTLE, AFTER
WHICH THE STEM WAS CUT.
• EXAMINE THE VISCOSITY OF THE PITCH BY THE
SPEED AT WHICH IT FLOWS FROM A FUNNEL
INTO A JAR.
• ONLY EIGHT DROPS HAS FALLEN IN 80 YEARS.
• THE VISCOSITY IS APPROXIMATED AS 100
BILLION TIMES THAT OF WATER.
Dr. Aldo Acevedo - ERC SOPS 17
 TYPES OF VISCOSITY

1. NEWTONIAN FLUID : Viscosity is

independent of the
shear stress

Typical Newtonian fluids

include water and thin motor
oils.

2. Non-Newtonian Fluids
The viscosity changes with the shear rate or the
shear force. Fluids may have a yield stress or 18

not.
 COMMON NON-NEWTONIAN BEHAVIOR

• shear thinning
• shear thickening
• yield stress

Think of some household items that have these characteristics.

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 PSEUDOPLASTIC – SHEAR THINNING

Increasing shear rate

Viscosity decreases as the shear rate increases:

include paints, emulsions, and dispersions of many
types. They flow instantly the stress is applied.
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 REASON FOR SHEAR THINNING.

Liquids often have structures, which are destroyed or aligned under stress.
Consequently, different sample particles are gliding easier over each other.
The inner resistance becomes less, the viscosity becomes lower. 21
RHEOGRAMS OF MATERIALS

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 PLASTIC FLOW - YIELD STRESS/POINT

• IN REAL FLUIDS A CRITICAL LEVEL OF STRESS MUST BE ATTAINED IN ORDER

TO INITIATE FLOW. BELOW THIS LEVEL IT BEHAVES AS A SOLID (PLASTIC)
AND ABOVE THIS IT BEHAVES AS A LIQUID.
• THE AMOUNT OF STRESS IS DESCRIBED AS THE YIELD POINT OR YIELD
STRESS.
• LIPSTICKS, DRILLING MUDS AND TOOTHPASTE ARE GOOD EXAMPLES OF
MATERIALS THAT HAVE A YIELD POINT.

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 BINGHAM PLASTIC : - YIELD POINT

The yield point is not a material constant but depends on

the measuring and analysis method used. 24
YIELD POINT 𝜏𝜏𝟎𝟎 (SPOKEN "TAU ZERO")

• 𝜏𝜏𝟎𝟎 IS DETERMINED BY EXTRAPOLATION OF THE FLOW

CURVE TOWARDS A LOW SHEAR RATE VALUE
• BINGHAM YIELD POINT

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26
 DILATANT – SHEAR THICKENING

Viscosity increases with increasing shear rate

In some cases these are dense suspensions of solid particles
in a fluid medium, which develop greater spacing between
particles during agitation. Most common is suspensions,
Penicillin, high solids with low particle sizes.
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 QUICKSAND – A NON-NEWTONIAN FLUID

• QUICKSAND IS A COLLOID HYDROGEL (SAND, CLAY AND

SALT WATER).
• WHEN UNDISTURBED BEHAVES AS A SOLID GEL, BUT MINOR
CHANGES IN THE STRESS WILL CAUSE A SUDDEN DECREASE
IN ITS VISCOSITY
• AFTER THE INITIAL PERTURBATION, WATER AND SAND
SEPARATE AND DENSE REGIONS OF SAND SEDIMENT
• HIGH VOLUME FRACTION REGIONS -> VISCOSITY INCREASES
• SUFFICIENT PRESSURE MUST BE APPLIED TO REINTRODUCED
WATER INTO THE COMPACTED SAND.
• THE FORCES REQUIRED TO REMOVE A FOOT FROM
QUICKSAND AT A SPEED OF 1 CM/S ARE ABOUT THE SAME
AS “THAT NEEDED TO LIFT A MEDIUM-SIZED CAR.” **
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** Khaldoun, A., E. Eiser, G.H. Wegdam and D. Bonn, “Rheology: Liquefaction of Quicksand Under Stress”,
Nature 437 pp 635 (2005)
 THIXOTROPY

• THIXOTROPY IS THE PROPERTY OF SOME NON-NEWTONIAN

PSEUDOPLASTIC FLUIDS TO SHOW A TIME-DEPENDENT CHANGE IN
VISCOSITY; THE LONGER THE SHEAR (PUMPING, STIRRING ETC) THE
THINNED THE FLUID. WHEN LEFT TO REST, THE VISCOSITY RETURNED.

• THIXOTROPIC FLUIDS HAVE A VISCOSITY THAT IS A FUNCTION OF TIME.

AT HIGH SHEAR RATES IT DECREASES WITH TIME. AT LOW OR ZERO SHEAR
RATES IT INCREASES WITH TIME.
• MANY GELS AND COLLOIDS ARE THIXOTROPY MAINTAINING A STABLE
FORM AT REST BUT BECOMING FLUID WHEN AGITATED.

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THIXOTROPY

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 DEGREE OF THIXOTROPY

The degree of thixotropy is

defined by the area under
the curve.

3 different types of hand cream.

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 VISCOSITY MEASUREMENT

• WHY MEASURE VISCOSITY?

• FOR CHEMICAL PROCESSING IT IS A CRITICAL PARAMETER. TO DETERMINE
THE BEHAVIOUR OF A FLUID AND PREDICT CHANGES BASED ON THE
FORMULA CHANGES AND PROCESSING CONDITIONS.
• AFTER A FLUID IS PROCESSED ITS VISCOSITY MAY CHANGE WITH TIME,
THIS INFORMATION MAY BE NECESSARY TO PRODUCE FURTHER
PROCESSING CONDITIONS.

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 VISCOMETER VS RHEOMETER

VISCOMETER – MEASURES VISCOSITY

RHEOMETER – MEASURES RHEOLOGICAL PROPERTIES

A RHEOMETER IS A VISCOMETER, BUT A VISCOMETER IS

NOT A RHEOMETER.

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 WHAT AND HOW TO MEASURE

1. PRAGMATIC ANALYSTS: ONLY NEED AN INSTRUMENT TO GENERATE A

NUMBER. QUALITY CONTROL AND PLANT PRODUCTION APPLICATIONS
ARE TYPICAL OF THIS CATEGORY.
2. THEORETICAL ANALYSTS: MAY KNOW THAT THEIR INSTRUMENT WILL
NOT GIVE THEM THE DEFINED SHEAR RATE AND ABSOLUTE VISCOSITY
BUT KNOW ENOUGH TO CORRELATE THE VISCOSITY WITH IMPORTANT
PRODUCT PARAMETERS.
3. ACADEMIC ANALYSTS: INSTRUMENTS WITH DEFINED GEOMETRIES AND
ALL MEASUREMENT PARAMETERS (SHEAR RATE AND SHEAR STRESS) ARE
KNOWN.

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 EXPERIMENTAL METHODS/ INSTRUMENTS

• ROTATIONAL RHEOMETERS
• PARALLEL PLATES (DISKS)
• CONE-AND-PLATE
• CONCENTRIC CYLINDER
• SPINDLE (BROOKFIELD)
• CAPILLARY (TUBE)
VISCOMETERS
• GLASS
• CUP.

• TUNING FORK VIBRO

RHEOMETER.
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 CAPILLARY FLOW – GLASS VISCOMETERS
Viscosity related to time taken for the liquid to flow from point E to
F. Constant for each capillary viscometer based on the geometry,
length of capillary, Vol, radius.
Used in comparison with a standard such as water or oils that the
viscosity is known.
𝜂𝜂
=
𝜌𝜌

As all values are constant apart from the time then it can be
reduced to
𝜂𝜂 = K .t where K is a constant for each viscometer.
However, there are lots of correlations needed.
Measures kinematic viscosity mm2/s

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 GLASS CAPILLARY

• ADVANTAGES:
1. SIMPLE – EXPERIMENTALLY AND EQUIPMENT SET-UP
2. INEXPENSIVE
3. HIGHER SHEAR RATES

• DISADVANTAGES:
1. MAY NEED MULTIPLE CORRECTIONS:
• END EFFECTS
• WALL SLIP
• TEMPERATURE
2. NO GOOD TEMPERATURE CONTROL
3. EACH ONE HAS A NARROW RANGE OF VISCOSITY.
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 ROTATIONAL TYPE :

• SHEAR IS GENERATED BETWEEN A FIXED AND MOVING SURFACE

The geometry of the spindle determines the

force that the fluid will exert on the spring. 38
 TYPES OF SPINDLES OR PLATES.

• THERE ARE DISC, CYLINDER, CONE AND PLATE, T-BAR AND PLATE AND
PLATE.
• SMALL CELL ADAPTORS ARE USED FOR VALUABLE MATERIALS OR WHERE
THERE IS LITTLE MATERIAL AVAILABLE. DEPENDING ON THE VISCOSITY
RANGE
• CRITICAL TO GOOD MEASUREMENT IS TEMPERATURE CONTROL. MOST
VISCOMETERS HAVE A WATER JACKET CONNECTED TO A WATER BATH
THAT CAN ACCURATELY CONTROL THE TEMPERATURE.

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40
 MEASUREMENT USING ROTATIONAL
VISCOMETERS
• DUE TO THE NON- NEWTONIAN BEHAVIOUR OF FLUIDS ALL PARAMETERS
MUST BE SPECIFIED FOR ACCURATE ANALYSIS. SPINDLE NUMBER,
REVOLUTION SPEED, HOW MANY REVOLUTIONS BEFORE THE READING IS
TAKEN.
• E.G. MEASUREMENT SPECIFIED AT 10 RPM; ON THE 5TH REVOLUTION AT
250 C.
• OR UNTIL A CONSISTENT RESULT IS OBTAINED.

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 PROCESS CONTROL & VISCOSITY.

1. MEASUREMENT
CHARACTERISE THE FLOW BEHAVIOUR OF A MATERIAL. INCOMING
INSPECTION: PROPERTIES SUCH AS MOLECULAR WEIGHT AND MOLECULAR
WEIGHT DISTRIBUTION MAY MODIFY THE RECIPE.

2. FOLLOW THE COURSE OF A CHEMICAL REACTION.

3. INLINE PROCESS CONTROL MEASUREMENT.
4. IN POLYMER FOLLOW THE COURSE OF CURING REACTION.

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 RHEOMETERS.

• COMPUTER CONTROLLED TO RAMP UP,

HOLD AND RAMP DOWN. ALLOWS
TO DETERMINE THIXOTROPIC
BEHAVIOUR. E.G. NAIL VARNISH. (SILLY
PUTTY).
• REGRESSION ANALYSIS: CASSON PLOT;
BINGHAM, ETC.
• YIELD STRESS.

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TUNING FORK VIBRO RHEOMETER.

For accurate measurement of very low viscosities.

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 EXAMPLE 1 COUGH SYRUP

Hand creams

Describe the fluid behaviour??

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 SUMMARY

• VISCOSITY OF FLUIDS IMPACTS BOTH PROCESSING AND PRODUCTS.

• RHEOLOGY IS THE STUDY OF THE FLOW OF MATERIALS.
• IMPACT OF SHEARING A FLUID CHANGES THE VISCOSITY: SHEAR
THINNING, SHEAR THICKENING, PSEUDOPLASTIC, THIXOTROPY.
• METHODS OF MEASUREMENT:
• IMPACT OF RHEOLOGY ON DIFFERENT PRODUCTS.
• HTTPS://WWW.BROOKFIELDENGINEERING.COM/-
/MEDIA/AMETEKBROOKFIELD/%E2%80%8CTECH%20SHEETS/MORE%20S
OLUTIONS%202017.PDF?LA=EN

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