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Quality Control II:

Instrumentation

IN-PROCESS QUALITY CONTROL

TEST FOR TABLETS

TABLET CHARACTERISTICS TABLET HARDNESS

Compressed tablets may be characterized
or described by a number of specifications. The resistance of the tablet to chipping
These include the: abrasion or breakage under conditions of
Diameter storage transportation and handling. Tablet
Shape usage depends on its hardness.
Thickness
Weight RULE OF THUMB
Hardness Used in the past to described a tablet to be
Disintegration time of proper hardness.
Dissolution (procedure) held the tablet between the 2nd
These characteristics along with color of and 3rd fingers and use the thumb as
the tablets tend to make them distinctive and fulcrum. Then, break the tablet with a sharp
identifiable with the active ingredient they snap.
contain.

MONSANTO or STOKES HARDNESS STRONG-COBB HARDNESS TESTER

TESTER
Manufactured and introduced in the
mid-1930s by Monsanto
Measures the force required to
break the tablet when a force
generated by a coil spring is applied
diametrically to the tablet.
The force is measured in kilograms
and when used in production a
hardness of 4 kg is considered to be
minimum for a satisfactory tablet.
Introduced in 1950.
Also measures the diametrically applied
force required to break tablet.
In this instrument the force is produced
by a manually operated air pump.
As the pressure is increased a plunger
is force against the tablet placed on
anvil.
The final breaking point is indicated on
a dial calibrated into 30 arbitrary units.
The values of the stokes and strong-
cobb instruments are not equivalent.
Values obtained with the Strong-cobb
have been found to be 1.6 times those
of the Stokes tester.

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PFIZER HARDNESS TESTER SCHLEUNIGER APPARATUS or HERBELEIN

Operates on the same mechanical Electrically operated test equipment
principle as ordinary pliers. eliminate the operator variability
The force required to break the tablet inherent in measurements.
is provided on a dial and may be
expressed in either kilograms or
pounds of force.
In an experimental comparison of
testers the Pfizer and the Stokes
testers were found to check each
other fairly well.
The strong-cobb tester was found to
give values 1.4 to 1.6 times the
absolute values on this instruments.

Importance of Tablet Hardness CAUSES of HARDNESS

Hardness (or more appropriately VARIATION:
crushing strength) determination are Varied volume of material
made throughout the tablet runs to
Inconsistent space between
determine the need for pressure
adjustments on the tableting punch and die
machine. Moisture content
If the tablet is too hard it may not Speed of compression
disintegrate in the required period of
time or meet the dissolution
Atmospheric condition
specifications. Type and amount of lubricant
If it is too soft it will not withstand the Uniformity of mix
handling during subsequent Tablet recrystallization
processing such as coating or
packaging and shipping operations Tablet machine pressure
and it will easily break. Aging of the machines

FRIABILITY: FRIABILATOR: (mechanism)

Another measure of tablets
strength
Shows how well a tablet resists
chipping and crumbling when
external stresses are applied.
Compressed tablets that loss less
than 0.5%-1% of their weight are
usually considered acceptable.
FORMULA:
Initial wt. Final wt.
% loss =---------------------------------------- X 100
Initial weight
Induce self-abrasion of the tablets
as the cylinder section rotates.
Tablets undergo shock as they fall
six inches on each turn.
Loss due to abrasion or fracture is
the measure of tablet friability.
After 4 minutes or 100 revolutions,
tablets are weighed and compared
to their initial weight.
When capping occurs, friability
values are no longer calculated.

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TABLET THICKNESS
Thickness can vary with no change in weight
because of the difference in the density of the
granulation and the pressure applied to the
tablets as well as the speed of tablet
compression.
Important in reproducing tablets identical in
appearance and also it ensures that every
production lot will be usable with selected
packaging components.
If the tablets are thicker than specified a
given number no longer may be contained in
the volume of a given size bottle.
Determined with a caliper or thickness gauge that
measures the thickness in millimeters.
5% may be allowed, depending on the size of the
tablet.
Also important in counting tablets using filling
equipment.
Some filling equipment uses the uniform thickness
of the tablet as a counting mechanism.
A column containing a known number of tablets
is measured for height; filling is accomplished by
continually dropping columns of tablets of the
same height into bottles.
If thickness varies throughout the lot the result
will be variation of the count.
Other pieces of filling equipment can
malfunction because of variation in tablet
thickness since tablets above specified
thickness may cause wedging of tablets in
previously adjusted depths of the counting slots.

IMPLICATIONS:
Packaging problem with tablets of variable
thickness.
Tablets with greater thickness have
reduced internal stresses thus, less
tendency to cap.
Changes in thickness are often results of
problem in the flow through the feeder or UNIFORMITY OF DOSAGE FORMS:
faulty deposition of granulation in the die.
Manufacturers set limits on thickness of TABLET WEIGHT
the tablets in order to ensure trouble free CONTENT UNIFORMITY
packaging.
Tablets that are inconsistent thickness
block the channels of counting machinery.
When tablets are thicker than normal, the
container proves to be inadequate to hold
the required count.

TABLET WEIGHT
The volumetric fill of the die cavity determines the weight of
the compressed tablet.
The weight of the tablet is the quantity of the granulation
that contains the labelled amount of the therapeutic agent.
The USP has provided tolerances for the average weight of
uncoated compressed tablets.
These are applicable when the tablets contains 50 mg AVERAGE WEIGHT PERCENT DIFFERENCE
or more of the drug substance or when the latter
comprises 50% or more of, by weight of the dosage form. 130 mg or less 10% (0.10)
Twenty tablets are weighed individually, the average
weight is calculated.
More than 130 mg through 324 mg 7.5% (0.075)
The variation from the average weight in the weights of
not more than two of the tablets must not differ by more
than the percentage listed; no tablet differs by more More than 324 mg 5% (0.05)
than double that percentage.
NOTE: Tablets that are coated are exempt from these
requirements but must conform to the test for content
uniformity.

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CAUSES of WEIGHT VARIATION:
The size and distribution of the granules
being compressed.
Poor flow resulting in incompletely filled
dies.
Poor mixing which is revealed by sounds
of strains during tablet ejection.
When lower punches are of unequal
lengths fill in each die varies because
the fill is volumetric.
TABLET DISINTEGRATION
and
TABLET DISSOLUTION
APPARATUS:
The apparatus consists of a basket rack
holding six plastic tubes holding six
tubes, open at the top and bottom; the
bottom of the tubes is covered with size
10 mesh screen.
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CONTENT UNIFORMITY
Ensure that every tablet contains the
amount of drug substance intended, with
little variation among tablets within a
batch.
Has been extended to monographs on all
coated and uncoated tablets and all
capsules intended for oral administration
where the range of sizes of the dosage
form available includes a 50mg or smaller
size in which case the test is applicable to
all sizes (50mg and larger/smaller) of that
tablet or capsules.
NOTE: Tablet monographs with a content
uniformity requirement do not have a
weight variation requirement.
TABLET DISINTEGRATION:
A measure of the time required under a
given set of conditions for a group of
tablets to disintegrate to particles.
Useful as a quality assurance tool for
conventional (non-sustained release)
dosage forms.
Particles are those that will pass through
a 10-mesh screen.
Used as a control for tablets intended to
be administered by mouth except for
tablets intended to chewed before being
swallowed or tablets designed to release
the drug substance over a period of time.
The basket rack is immersed in a bath of
suitable liquid held at 37 o C preferably in a 1L
beaker.
The rack moves up and down in the fluid at a
specified rate.
The volume of the fluid is such that on the
upward stroke the wire mesh remains at least
2.5 cm below the surface of the fluid and
descends to not less than 2.5 cm from the
bottom on the downward stroke.
Tablets are placed in each of the six cylinders
along with a plastic disc over the tablet unless
otherwise directed in the monograph.
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The end point of the test is indicated when any

residue remaining is a soft mass with no
palpably soft core.
The plastic disc help to force any soft mass
that forms through the screen.
For compressed, uncoated tablets the testing
fluid is usually water at 37 o C but in some
cases monographs direct the simulated
Gastric Fluid TS be used.
If one or two tablets fail to disintegrate the
test is to be repeated using 12 tablets.
Of the 18 tablets then tested, 16 must have
disintegrated within the given period of time.
The conditions of the test are varied somewhat
for coated tablets buccal tablets, and
sublingual tablets.
PARTS of a DISINTEGRATION APPARATUS:
BASKET-RACK ASSEMBLY:
Consists of six-open ended
transparent tubes, each 7.75 +/-
0.25 cm long and having an inside
diameter of approximately 21.5 mm
and a wall approximately 2 mm thick.
Tube are held in a vertical position by
2 plastic plates each about 24 mm in
diameter, equidistant from the center
of the plate and equally spaced from
one another.

MESH
Attached under the surface of the lower plate wire DISSOLUTION TEST:
gauge and metal gauge woven stainless wire cloth
For certain tablets the monographs direct
having a plain square weave.
The parts are assembled and rigidly held by means of compliance with limits on dissolution rather
three bolts passing the 2 plastic plates. than disintegration.
Measures the amount of time required for a
DISKS
The use of disks is permitted only where the specified given percentage of the drug substance in a
in the monograph. tablet to go into solution under a specified
If specified, each tube is provided with a slotted and
set of conditions.
perforated cylindrical disk 15 +/- 0.15 mm thick and
20.7 +/- o.15 mm in diameter.
The disk is made of suitable transparent plastic
material having a specific gravity of 1.18 - 1.2
Equally spaced on the sides are four notches that form
V-shaped planes that are perpendicular to the ends of
the cylinder.

USP APPARATUS 2:
DISSOLUTION APPARATUS DESIGN:
Is similar to apparatus 1 except that a
USP APPARARUS 1:
metallic paddle usually coated with an inert
Consists of 1000 ml covered cylindrical
material, is used in place of the basket
vessel made of glass or an inert material,
assembly.
a cylindrical 40-mesh stainless-steel
The paddle is formed of a blade welded to a
basket connected to metallic drive shaft,
shaft that can be connected to the speed-
and a speed regulator motor.
regulated motor.
The assembly in a water bath that permits
The tablets or capsules are dropped freely to
a constant temperature inside vessel of
the bottom of the flask, and the paddle is
37 degrees celsius +/- 0.5 degrees during
rotated at the specified speed.
the test. The tablets or capsules is
(Note: Both USP Apparatus 1 and 2 have to
inserted into an individual baskets, and
be calibrated before use with two types of
the baskets are lowered into the
calibrators recommended by the USP; a
dissolution vessels.
disintegrating type (prednisone) and a non-
disintegrating type (salicylic acid). The
calibrators are available from the USP.

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APPARATUS 3:
Consists of set of cylindrical, flat-
bottomed glass vessels; a set of glass
reciprocating cylinders; stainless steel
fittings and screens to fit both the top
and bottom of the glass cylinders; and a
motor and drive assembly to reciprocate
the cylinders vertically inside the vessels.
The apparatus also has the ability to
index the cylinders to a different row of
vessels. The vessels are partially
immersed in a suitable water bath at 37
degrees C +/- 0.5 degrees C.
APPARATUS 4:
Consists of a reservoir and a pump
containing the dissolution medium. A
flow through cell, mounted vertically,
containing the tablet or capsule has
the dissolution medium pump
upward through the flow through cell
in which glass beads are placed to
maintain laminar flow.
APPARATUS 5:
It uses a standard paddle and
utilize a typical volume of 900 ml
as the dissolution medium
modifications are disc design and
the volume.

APPARATUS 6:
Special cylinder is used with
typical volume of 900 ml as the
dissolution medium.

Apparatus 7:
Uses a reciprocating
disk and a sample
holder sequential
media tubes which
has a typical volume
of 50-400 ml.

Quiz and Exam

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