This document provides an overview of preformulation studies for intramuscular injections. It discusses various parameters studied in preformulation including organoleptic properties, particle size, shape and distribution, powder flow properties, FTIR spectroscopy, DSC, X-ray diffraction, solubility, partition coefficient, and the effect of temperature on solubility. It also describes stability studies conducted at different stages including stress testing, accelerated and long-term testing to determine shelf life and storage conditions. The testing scope for liquid injectables includes parameters like pH, clarity, assay, degradation products, and functionality of container closure systems. Finally, it discusses climatic zones for stability testing and the hygroscopic nature of some drug substances.
2. Intramuscular (also IM or im) injection is
Intramuscular injection
the injection of a substance directly into a muscle.
In medicine, it is one of several alternative methods for the
administration of medications (see route of administration).
It is used for particular forms of medication that are
administered in small volumes
Intramuscular injection
Depending on the chemical properties of the drug, the
medication may either be absorbed fairly quickly or more
gradually. Muscles have larger and more blood vessels than
subcutaneous tissue and injections here usually have faster
rates of absorption than subcutaneous
injections or intradermal injections.[1] Depending on the
injection site, an administration is limited to between 2 and 5
milliliters of fluid.
2
3. Examples of medications that are sometimes administered
intramuscularly are:
Haloperidol (Haldol)
Chlorpromazine (Thorazine)
Lorazepam (Ativan)
Fulvestrant (Faslodex)
Codeine
Morphine
Methotrexate
Metoclopramide
Olanzapine
Streptomycin
Diazepam
Prednisone
Penicillin
Interferon beta-1a
Sex hormones, such as testosterone, estradiol valerate,
and medroxyprogesterone acetate (as Depo Provera)
Dimercaprol
3
4. Forms of IM injections
1. Injectable Solutions
2. Injectable Suspentions
3. Dry powders
4
7. COLOR
Color is generally a function of a drug’s inherent
chemical structure relating to a certain level of
unsaturation.
Color intensity relates to the extent of conjugated
unsaturation as well as the presence of chromophores.
Some compound may appear to have color although
structurally saturated.
7
8. Odour
The substance may exhibit an inherent odor
characteristic of major functional groups present.
Odor greatly affects the flavor of a preparation or
food stuff.
Taste:-
If taste is considered as unpalatable, consideration is
to be given to the use of a less soluble chemical form
of the drug.
The odour and taste may be suppressed by using
appropriate flavors and excipients or by coating the
final product.
8
9. PARTICLE SIZE
Particle size is characterized using these terms :
i. Very coarse (#8)
ii. Coarse (#20)
iii. Moderately coarse (#40)
iv. Fine (#60)
v. Very fine (#80)
9
10. PARTICLE SIZE
Particle size can influence variety of
important factors :
- Dissolution rate
- Suspendability
- Uniform distribution
- Penetrability
- Lack of grittiness
10
11. Methods to Determine Particle Size
Sieving
Microscopy
Sedimentation rate method
Light energy diffraction
Laser holography
Cascade impaction
11
12. Methods to Determine Particle Size
1. Sieving method :
Range : 50 – 150 µm
Simple, inexpensive
If powder is not dry, the apertures get clogged.
2. Microscopy :
Range : 0.2 – 100 µm
Particle size can be determined by the use of
calibrated grid background.
Most direct method.
Slow & tedious method.
12
13. 3. Sedimentation method :
Range : 1 - 200 µm
Andreasen pipette is used.
Particle size is calculated by stoke’s law :
dst =
Where,
h = distance of fall in time, t
no = viscosity of the medium
ρs = density of the particles
ρ0 = density of the dispersion medium
g = acceleration due to gravity
18 η0 h
(ρs -ρ0)
gt
13
14. 4. Light energy diffraction :
Range : 0.5 – 500 µm
Particle size is determined by the reduction in light
reaching the sensor as the particle, dispersed in a liquid
or gas, passes through the sensing zone.
Quick & fast.
5. Laser holography :
Range : 1.4 – 100 µm
A pulsed laser is fired through an aerosolized particle
spray & photographed in three dimensional with
holographic camera, allowing the particles to be
individually imaged & sized.
14
15. 6. Cascade impaction :
The principle that a particle driven by an airstream
will hit a surface in its path, provide that its inertia
is sufficient to overcome the drug force that tends
to keep in it in airstream.
15
16. 16
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17. 17
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The industry preferred laser diffraction analyzer ideal for particle size analysis.
18. 18
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delivering unsurpassed resolution. The
Bluewave measures particle size from 0.01
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19. 19
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What sets the TRI-BLUE apart is it’s
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20. POWDER FLOW PROPERTIES
Powder flow properties can be affected by change in particle
size, shape & density.
The flow properties depends upon following-
1. Force of friction.
2. Cohesion between one particle to another.
Fine particle posses poor flow by filling void spaces
between larger particles causing packing & densification of
particles..
By using glident we can alter the flow properties.
e.g. Starch, Talc.
20
21. By determining Angle Of
Repose.
A greater angle of repose
indicate poor flow.
It should be less than 30°.
& can be determined by
following equation.
tan θ = h/r.
where, θ = angle of
repose.
h=height of pile.
r= radius.
Angle Of
Repose
( In degree)
Type Of
Flow
<25 Excellent
25-30 Good
30-40 Passable
>40 Very poor
21
22. Measurement of free flowing powder by compressibility.
Also known as Carr's index.
CARR’S INDEX(%) =(TAPPED DENSITY – POURED DENSITY) X 100
TAPPED DENSITY
It is simple, fast & popular method of predicting powder
flow characteristics.
22
23. Determination Of Powder Flow Properties
Carr’s Index Type of flow
5-15 Excellent
12-16 Good
18-21 Fair To Passable
23-35 Poor
33-38 Very Poor
>40 Extremely Poor
23
25. Particle shape will influence the surface area, flow of
particles, packing & compaction properties of the
particles.
A sphere has minimum surface area per unit volume.
Therefore, these properties can be compared for
spheres & asymmetric particles, in order to decide the
shape.
The following expression can be obtained:
Property Sphere particle
surface area πds
2 αs x dp
2
volume (1/6)πds
3 αv x dp
3
Cont…
25
26. PARTICLE SHAPE
Therefore,
surface area = πds
2 = αs x dp
2
Volume = (1/6)πds
3 = αv x dp
3
Solving for αs & αv by equating the appropriate properties
provides:
αs =
πds
2 & αv =
πds
3
When particle shape is spherical, the ds = dp
Thus, αs = π = 3.124 & αv = π/6 = 0.524
Therefore, Shape factor = αs = 3.124 = 6
αv 0.524
Cont…
dp2 6 dp3
26
27. Fourier Transform Infra Red Spectroscopy study
(FTIR)
Fourier Transform Infra Red Spectroscopy study was carried out
to know any possible interference between the drug and
excipients. The present study was in wide usage from many a
years in formulation development.
27
28. Differential Scanning Calorimetry Differential
scanning calorimetry(DSC) is a widely used
technique within the pharmaceutical industry because
the range of phase transitions it can measure usually
allows near complete physical characterization of a
new active principal early during preformulation.
DSC technology is constantly evolving and
improving and three recent derivatives have become
popular. These are:
• Temperature-modulated DSC
• High-sensitivity DSC
• Fast-scan DSC
28
29. X-ray diffraction
Working :
When beam of nonhomogenous X-ray is allow to
pass through the crystal, X-ray beam is diffracted &
it is recorded by means of photographic plate.
Diffraction is due to crystal which acts as 3
dimensional diffraction grating toward X-ray.
29
31. Random orientation of crystal lattice in the powder
causes the X-ray to scatter in a reproducible pattern
of peak intensities.
The diffraction pattern is characteristic of a specific
crystalline lattice for a given compound.
31
32. An amorphous form does not produce a pattern
mixture of different crystalline forms.
Single – Crystal x-ray provide the most complete
information about the solid state.
32
33. Ionization constant (pKa)
Can be calculated by Henderson Hasselbach
equation-
For acidic drugs….pH= pKa+ log [ionized drug]
[unionized drug]
For basic drugs….pH= pKa+ log[unionized drug]
[ionized drug]
33
34. pH Solubility Profile
The solubility of acidic or basic drug will show
difference in solubility with changes in pH.
pH solubility profile of a drug can be established
by running the equilibrium solubility experiment
within pH range of 3-4.
34
35. Partition Coefficient
It is the ratio of unionized drug distributed
between organic and aqueous phase at equilibrium.
P o/w = ( C oil / C water )equilibrium
35
36. Effect Of Temperature
The heat of solution Hs, represents the heat
released or absorbed when a mole of solute is
dissolved in large quantity of solvent.
Endothermic reaction
Exothermic reaction
36
37. Provide a evidence on how the quality of a drug
substance or drug product varies with time under the
influence of a variety of environmental factors such
as….. temperature, Humidity and light.
Establish a re-test period for the drug substance or a
shelf life for the drug product and recommended storage
conditions.
Because physical, chemical or microbiological changes
might impact the efficiency and security of the final
product
37
38. Stability Studies are preformed on ...
Drug Substances (DS) The unformulated drug
substance that may subsequently be formulated with
excipients to produce the dosage form.
Drug Products (DP) The dosage form in the final
immediate packaging intended for marketing…….
controlled and documented determination of
acceptable changes of the drug substance or drug
product
38
39. Physical changes
• Appearance
• Melting point
• Clarity and color of solution
• moisture
• Crystal modification (Polymorphism)
• Particle size
Chemical changes
• Increase in Degradation
• Decrease of Assay
Microbial changes
39
40. Forced degradation studies
Acidic & Basic conditions.
Dry heat exposure
UV radiation exposure
Influence of pH
Influence of temperature
Influence of ionic strength
40
42. Stability studies at different stages
Stress- and accelerated Testing with drug substances
Stability on pre-formulation batches
Stress testing on scale-up Batches
Accelerated and long term testing for registration
On-going Stability testing
Follow-up Stabilities
42
43. Scope
• Solubility Profile
• Hygroscopicity
• Thermal stability
(Melting point,
Polymorphism)
• Chemical stability
1 Batch
Up to 3 month
Scope
• Determination of expire date
• Determination of preliminary
specifications
• Release of clinical batches
• Monitoring of samples during the clinical
phases
• Definition of storage conditions
• Definition of Tests for registration
stability
Up to 36 month
Selection of samples
• API, excipient, batches
Scope
• Appearance
• Appropriate physical-chemical parameter
• Assay / Degradation products
Up to 3 month
Stability studies at different stages
43
44. Testing scope for
LIQUID FORMS for inj. and PARENTRAL
Physical-chemical properties
– pH
– Loss on weight
– Color & clarity of solution
Chemical properties
– Assay
– Degradation products
– Degradation preservatives
– Content antioxidants
Microbial properties
Container closure system properties
– Functionality tests
44
45. Climatic Zones / Storage conditions
Climatic Zone
Countries
Calculated data
Temp. MKT humidity
°C °C % r.h.
Derived data
Temp humidity
°C % r.h.
Climatic Zone I
"Temperate"
Japan, United Kingdom,
Northern Europe,
Canada, Russia, United
States
20 20 42 21 45
Climatic Zone II
"Mediterranean,
Subtropical"
Japan, United States,
Southern Europe
26.4 22 52 25 60
45
46. Climatic Zones / Storage conditions
Climatic Zone
Countries
Calculated data
Temp. MKT humidity
°C °C % r.h.
Derived data
Temp humidity
°C % r.h.
Climatic Zone III
"Hot, dry"
Iran, Iraq, Sudan
26,4 27,9 35 30 35
Climatic Zone IV
"Hot, humid"
Brazil, Ghana, Indonesia,
Nicaragua,
Philippines
26,7 27,4 76
30 70
46
47. HYGROSCOPICITY
Many drug substances , particularly water soluble salt forms
have a tendency to adsorb atmospheric moisture .
adsorption can depend upon the humidity
temperature
surface area
mechanism for moisture
uptake .
The changes in moisture level can greatly influence many
important parameters , such as chemical stability , flow
ability and compatibility .
.
47
48. 48
PROCEDURE :
To carry out a study , samples are accurately weighed in a tarred
containers and placed at various humidity conditions for periods up
to 2 weeks. Weight gain or loss is measured at predetermined time
intervals until equilibrium is reached .
If the drug is very hygroscopic or unstable in the presence of
moisture , the drug would have to be stored under dry conditions .
High hygroscopicity is undesirable for many reasons, including
Handling problems,
requirement of special storage conditions, chemical and physical
stability problems
49. MELTING POINT :-
Defined as the temperature at which the solid and liquid
phases are in equilibrium .
the melting point of a drug can be measured using three
techniques:-
1) Capillary melting
2) Hot stage microscopy
3) Differential scanning calorimetric or thermal analysis.
Capillary melting :-
Capillary melting gives information about the melting range
but it is different to assign
an accurate melting point.
49
50. Hot stage microscopy:-
This the visual observation of melting under a microscope
equipped with a heated and lagged sample stage. The heating
rate is controllable and up to three transitions can be
registered. These values are more accurate .
Differential scanning calorimetric and thermal analysis :-
Differential thermal analysis (DTA) measures the temperature
difference between the sample and a reference as a function of
temperature or time when heating at a constant rate .
Differential scanning calorimetric (DSC) is similar to DTA
except that the instrument measures the amount of energy
required to keep the sample at the same temperature as the
reference . 50
51. 4. SOLUBILITY
Solubility > 1 % w/v
=> no dissolution-related absorption problem
Highly insoluble drug administered in small doses
may exhibit good absorption
Unstable drug in highly acidic environment of
stomach, high solubility and consequent rapid
dissolution could result in a decreased
bioavailability
The solubility of every new drug must be
determined as a function of pH over the
physiological pH range of 1 - 8
51
52. 4.1 Determination of Solubility
Solvent
(fixed volume)
Adding solute in small
incremental amounts
Vigorously
shaking
Undissolved
solute particles ?
Examine
visually
YesNo
Total amount
added up
Estimated solubility
4.1.1 Semiquantitative determination:
“LAW OF MASS ACTION”
52
53. 4.1.2 Accurately Quantitative determination:
Excess drug powder
150 mg/ml (15 %)
+ solvent
Ampul/vial
(2-5 ml)
Shaking at constant
temperature
(25 or 37 oC)
2 - 8 oC ?
Membrane filter
0.45 mm
Determine the drug
concentration in the
filtrate
Determine the drug
concentration in the
filtrate
Determine the drug
concentration in the
filtrate
Membrane filter
0.45 mm
Membrane filter
0.45 mm
Same
concentration ?
The first few ml’s of the filtrates should be
discarded due to possible filter adsorption
Solubility
48 hr
72 hr
? hr
53
54. 4.1.3 Unique Problems in Solubility
Determination of Poorly Soluble Compounds
Solubilities could be overestimated due to the
presence of soluble impurities
Saturation solubility is not reached in a reasonable
length of time unless the amount of solid used is
greatly in excess of that needed to saturation
Many compounds in solution degrade, thus making
an accurate determination of solubility difficult
Difficulty is also encountered in the determination
of solubility of metastable forms that transform to
more stable forms when exposed to solvents
54
55. 4.2 pH-Solubility Profile
Excess drug
powder
Stir in beaker
with distilled
water
Continuous
stirring of
suspension
Add
acid/base
Measure
pH of
suspension
Determine the
concentration
of drug in
the filtrate
SOLUBILITY pH
Filter Stirring
55
56. Poorly-soluble weakly-acidic drugs:
pH = pKa + log [(St - So)/So] (2)
Poorly-soluble weakly-basic drugs:
pH = pKa + log [So/(St - So)] (3)
where
So = solubility of unionized free acid or base
St = total solubility (unionized + ionized)
56
58. •Material testing
Container strength testing should be a part of all container selection
criteria. Regardless of whether or not the container is a standard or
custom-designed vial, cartridge, or syringe, the design has likely been
checked for high stress points through the use of finite element methods
(FEM).
•While the materials used in parenteral pharmaceutical containers (glass,
cyclic olefin polymers) have strength well above applied forces, the
strength of these containers depends on the surface quality and location
of applied force.
•Glass containers that experience a significant amount of glass-to-glass
or glass-to-metal contacts can experience enough reduction in glass
strength to noticeably increase the number of glass container breakage
events.
58
59. •For auto-injectors, the containers should be assessed to
determine if they can withstand the supplied delivery force
(spring, gas) to a desired failure rate of few ppm across
multiple lots of the container to ensure minimized risk of
failure of the device in the field.
•For syringes, the containers should be assessed across
multiple lots at the flange, body and cone. Samples are
subjected to overloading until it causes breakage. Thus the
container defect rate under “normal” conditions can be
estimated with high confidence based on these statistical
evaluations. A typical syringe requires at least three testing
geometries (flange, body and cone).
59
61. Aqueous vehicle :
1.Water For Injection(WFI) USP : Highly purified water
used as a vehicle for injectable preparations which will
be subsequently sterilized.
USP requirement include not more than 10 parts per
million of total solids.
pH of 5.0 to 7.0 WFI may prepared by either distillation
or reverse osmosis.
Stored for less than 24hr at RT or for longer times at
specific temperatures. Should be meet USP pyrogen test
It may not contain any added substances.
Stored in chemically resistant tank.
61
62. Bacteriostatic Water for Injection (BWFI) : This
type of water used for making parenteral solutions
prepared under aseptic conditions and not
terminally sterilized. Need to meet USP sterility
test. It can contain an added bacteriostatic agent
when in containers of 30ml or less
62
63. Sterile Water for Injection USP
SWFI containing one or more
suitable bacteriostatic agents.
Multiple-dose containers not
exceeding 30 ml. They are
permitted to contain higher levels
of than WFI because of the possible
leaching of glass container. Sterile
Water for Irrigation. Wash wounds,
surgical incisions, or body tissue
63
65. ADDED SUBSTANCES
(ADDITIVES)
Antimicrobials:
-Used to prevent the growth of micro-organisms
-Generally used in multiple dose vials
Ideal Features :
Arrest the growth of microbes
Compatibility with therapeutic ingredient and other
additives
Compatible with packaging material
No toxic effects to the patient
Stability throughout the shelf life of patient
67. Antioxidants:
These are the substances that prevent
degradation of therapeutic agent which occur
due to accelerated conditions of heat sterilization
and during storage.
Ex: A) Reducing agents:
Ascorbic acid -- 0.02 – 0.1 %
Sodium bisulphite-- 0.1 – 0.15 %
Sodium metabisulphite-- 0.1 – 0.15 %
B) Blocking agents:
Ascorbic acid esters-- 0.01 – 0.015%
Continued…
69. Buffers:
Added to maintain pH and thus results in
stability
Change in pH may cause degradation of the
products
Most ideal pH of parenteral preparation is
7.4
Buffer should not affect the
pharmacological activity and solubility of
the drug
pH of the buffer above 7 results in necrosis
of the tissues and below pH 3 causes pain
in the tissues.
Acetate and phosphate buffers are
generally used
Continued…
70. Chelating agents:
Used to form the complex with the metallic ions present
in the formulation so that the ions will not interfere during
manufacture of formulation
They form a complex which gets dissolved in the solvents
Raw materials, solvents, containers, rubber closures and
equipments employed act as sources of heavy metal
contamination
Examples:
Ethylenediamine tetra-acetic acid --- 0.00368 - 0.05
%
Disodium calcium edetate --- 0.04 %
Tetrasodium edetate --- 0.01 %
Continued…
71. Continued…
Protectants :
Cryoprotectants:
These are used to inhibit the loss of integrity of
the active substance caused due to freezing
EX : PEG – prevents the damage of enzymes
( lactate dehydrogenase, Phospho fructokinase)
Lyoprotectants :
These are used to prevent the loss of activity of
therapeutic agent.
EX : Sugar – sucrose, trehalose
72. Surfactants:
They enhance the solubility of the drugs
Used to disperse a water insoluble drug to
form a colloidal dispersion
Ex: lecithin, propylene glycol, povidone,
glycerin
Inert gases :
Product stability and maintenance of
product integrity
During manufacture and filling of
parenterals
In filled vials, air in head space is filled with
nitrogen or argon before sealing . Ex –
ergotamine injection
Examples : Argon, nitrogen
73. Continued…
Stabilizers:
As parenterals are available
in solution form they are most
prone to unstabilize, So used
to stabilize the formulation
Examples:
Glycerin – 1.5 – 2.25
%
Niacinamide – 1.25 -2.5 %
Sodium saccharin – 0.03
%
74. Solubilizing agents:
- Used to increase solubility of slightly
soluble drugs
- They act by any one of the following:
solubilizers,
emulsifiers or
wetting agents.
Examples:
Dimethylacetamide,
Ethyl alcohol
Glycerin
PEG – 300
Polysorbate 20, 40, 80
75. Continued…
Tonicity- adjusting agents:
Helps in maintaining tonicity with the body fluids
Used to reduce the pain of injection
Parenterals that deliver into spinal ophthalmic
must be isotonic
For subcutaneous preparations, isotonicity
maintenance reduces irritation.
Isotonicity depends on permeability of a living
semipermeable membrane
◦ Hypotonic : Swelling Of Cells (Enlargement)
◦ Hypertonic: Shrinking Of Cells (Reduction)
Examples:Glycerin, Lactose, Mannitol,
Dextrose, Sodium chloride, Sorbitol
76. Competitive binders:
They are used to prevent the interaction
between proteins and glassware
Care must be taken while selecting the added
substance as they can induce reaction that
may inactivate active pharmaceutical
ingredient
Bulking agent :
These substances help to increase the weight
of the therapeutic agent.
EX : Sugars – sucrose, lactose, mannitol
79. Measurement of Viscosity
The usual method for measurement of viscosity involves the
determination of the time required for a given volume of liquid to
flow through a capillary.
Many capillary-tube viscosimeters have been devised, but
Ostwald and Ubbelohde viscosimeters are among the most
frequently used.
A particularly convenient and rapid type of instrument is a
rotational viscosimeter, which utilizes a bob or spindle immersed
in the test specimen and measures the resistance to movement of
the rotating part.
Different spindles are available for given viscosity ranges, and
several rotational speeds generally are available. 79
80. • Other rotational instruments may have a stationary bob and a
rotating cup.
• The Brookfield, Rotouisco, and Stormer viscosimeters are
examples of rotating-bob instruments, and the MacMichael is an
example of the rotating-cup instrument.
• Numerous other rotational instruments of advanced design with
special devices for reading or recording, and with wide ranges
of rotational speed, have been devised.
• Where only a particular type of instrument is suitable, the
individual monograph so indicates.
• For measurement of viscosity or apparent viscosity, the
temperature of the substance being measured must be accurately
controlled, since small temperature changes may lead to marked
changes in viscosity.
• For usual pharmaceutical purposes, the temperature should be
held to within ±0.1 .
80
81. Common methods for determination of viscosity
Method I (U tube viscometer)
Apparatus
The apparatus consists of a glass
U-tube viscometer made of clear
borosilicate glass and constructed
in accordance with the dimensions
given in official books.
The monograph states the size of
viscometer to be used.
81
82. Method
• Fill the viscometer with the liquid being
examined through tube L to slightly above the
mark G, using a long pipette to minimise wetting
the tube above the mark.
• Place the tube vertically in a water bath and when
it has attained the specified temperature, adjust
the volume of the liquid so that the bottom of the
meniscus settles at the mark G.
• Adjust the liquid to a point about 5 mm above the
mark E.
• After releasing pressure or suction, measure the
time taken for the bottom of the meniscus to fall
from the top edge of mark E to the top edge of
mark F.
82
83. Method II (Capillary viscometer method)
(Ph. Eur. method 2.2.9)
• The determination of viscosity using a suitable
capillary viscometer is carried out at a
temperature of 20 ± 0.1 °C, unless otherwise
prescribed.
• The time required for the level of the liquid to drop
from one mark to the other is measured with a
stop-watch to the nearest one-fifth of a second.
• The result is valid only if two consecutive readings
do not differ by more than 1 per cent.
• The average of not fewer than three readings gives
the flow time of the liquid to be examined.
• 83
84. Calculate the dynamic viscosity h in millipascal
seconds using the formula:
K = constant of the viscometer
ρ = density of the liquid to be examined expressed in
milligrams per cubic millimeter
t = flow time, in seconds, of the liquid to be
examined.
The constant k is determined using a suitable
viscometer calibration liquid.
84
85. Method III (Rotating viscometer method)
(Ph. Eur. method 2.2.10)
• The principle of the method is to measure the force acting on
a rotor (torque) when it rotates at a constant angular velocity
(rotational speed) in a liquid.
• Rotating viscometers are used for measuring the viscosity of
Newtonian (shear-independent viscosity) or non-Newtonian
liquids (shear dependent viscosity or apparent viscosity).
• Rotating viscometers can be divided in 2 groups, namely
absolute and relative viscometers.
• In absolute viscometers the flow in the measuring geometry
is well defined. The measurements result in absolute
viscosity values, which can be compared with any other
absolute values.
85
86. In relative viscometers the flow in the measuring
geometry is not defined.
The measurements result in relative viscosity
values, which cannot be compared with absolute
values or other relative values if not determined by
the same relative viscometer method.
Different measuring systems are available for given
viscosity ranges as well as several rotational
speeds.
86
87. Apparatus
The following types of instruments are most
common.
Concentric cylinder viscometers (absolute
viscometers)
In the concentric cylinder viscometer (coaxial
double cylinder viscometer or simply coaxial
cylinder viscometer), the viscosity is
determined by placing the liquid in the gap
between the inner cylinder and the outer
cylinder.
Viscosity measurement can be performed by
rotating the inner cylinder (Searle type
viscometer) or the outer cylinder (Couette type
viscometer), as shown in Figures.
87
88. Cone-plate viscometers (absolute viscometers)
• In the cone-plate viscometer, the liquid is
introduced into the gap between a flat disc and a
cone forming a define angle.
• Viscosity measurement can be performed by
rotating the cone or the flat disc, as shown in
Figures below. For laminar flow, the viscosity (or
apparent viscosity) h expressed in Pascal-seconds
is given by the following formula:
88
89. Spindle viscometers (relative viscometers)
In the spindle viscometer, the viscosity is determined
by rotating a spindle (for example, cylinder- or disc-
shaped, as shown in Figures) immersed in the liquid.
Relative values of viscosity (or apparent viscosity) can
be directly calculated using conversion factors from
the scale reading at a given rotational speed.
89
90. In a general way, the constant k of the apparatus
may be determined at various speeds of rotation
using a certified viscometer calibration liquid. The
viscosity ƞ then corresponds to the formula:
90
91. Method
• Measure the viscosity (or apparent viscosity)
according to the instructions for the operation of the
rotating viscometer.
• The temperature for measuring the viscosity is
indicated in the monograph.
• For non-Newtonian systems, the monograph
indicates the type of viscometer to be used and if
absolute viscometers are used the angular velocity
or the shear rate at which the measurement is
made.
• If it is impossible to obtain the indicated shear rate
exactly, use a shear rate slightly higher and a shear
rate slightly lower and interpolate.
91
92. • With relative viscometers the shear rate is not the
same throughout the sample and therefore it cannot
be defined.
• Under these conditions, the viscosity of non-
Newtonian liquids determined from the previous
formula has a relative character, which depends on
the type of spindle and the angular velocity as well
as the dimensions of the sample container (Ø =
minimum 80 mm) and the depth of immersion of
the spindle.
• The values obtained are comparable only if the
method is carried out under experimental conditions
that are rigorously the same.
92
93. Method IV (Falling ball viscometer method)
(Ph. Eur. method 2.2.49)
The determination of dynamic viscosity of Newtonian
liquids using a suitable falling ball viscometer is
performed at 20 ± 0.1 °C, unless otherwise prescribed
in the monograph.
The time required for a test ball to fall in the liquid to
be examined from one ring mark to the other is
determined.
If no stricter limit is defined for the equipment used
the result is valid only if 2 consecutive measures do
not differ by more than 1.5 per cent.
93
94. Apparatus
• The falling ball viscometer consists of: a glass tube
enclosed in a mantle, which allows precise control of
temperature;
• six balls made of glass, nickel-iron or steel with
different densities and diameters.
• The tube is fixed in such a way that the axis is
inclined by 10 ± 1° with regard to the vertical.
• The tube has 2 ring marks which define the distance
the ball has to roll.
• Commercially available apparatus is supplied with
tables giving the constants, the density of the balls
and the suitability of the different balls for the
expected range of viscosity.
•
94
95. Method
• Fill the clean, dry tube of the viscometer,
previously brought to 20 ± 0.1 °C, with the liquid
to be examined, avoiding bubbles.
• Add the ball suitable for the range of viscosity of
the liquid so as to obtain a falling time not less
than 30 s.
• Close the tube and maintain the solution at 20 ±
0.1 °C for at least 15 min. Let the ball run through
the liquid between the 2 ring marks once without
measurement.
• Let it run again and measure with a stop-watch, to
the nearest one-fifth of a second, the time
required for the ball to roll from the upper to the
lower ring mark. Repeat the test run at least 3
times.
95
96. Calculate the dynamic viscosity ƞ in millipascal
seconds using the formula:
k = constant, expressed in millimeter squared per
second squared,
ρ1 = density of the ball used, expressed in grams per
cubic centimeter,
ρ2 = density of the liquid to be examined, expressed
in grams per cubic centimeter.
t = falling time of the ball, in seconds.
96
97. Zeta Potential Analyzer
Zeta Potential Analyzer: ZEECOM
zeta potential and particle size measurements with real time
observation!
•Zeta potential measurement in microscopic electrophoresis
•Particle identification and automatic tracking in image processing
•Direct observation of nanopaticles by scattered light
97