ANALYTICAL INSTRUMENTS

What is an analytical instrument?

Hardness tester for Tablets

Tablet hardness is associated with tablet properties such as density and porosity and depends on the
shape, chemical properties, binding agent and punch pressure applied during compression. It is a non-
official quality control technique or method. It is not prescribed by I.P. Hardness of a tablet can be
said to be its ability to resist deformational or crushing force.

The first small and portable hardness tester was manufactured and introduced by Monsanto in the
mid-1930s.

Monsanto hardness tester:

It is now designated as either the Monsanto or Stokes hardness tester. The instrument measures the
force required to break the tablet when the force generated by a coil spring is applied diametrically to
the tablet. Hardness tester generally measures the tablet crushing strength. Other devices used to test
hardness are Pfizer tester, Strong-cobb tester, schleuniger tester and erweka tester.

Pfizer Tester:
It works on the mechanical principle as a pair of pliers.
Tablet is compressed between holding anvil & a piston connected to the direct force measuring gauge.
Erweka Tester:

Tablet is placed on the lower anvil & the anvil is adjusted so that the tablet just touches the upper test
anvil. The applied breaking force between the anvils is directly measured by the gauge.

Schleuniger Tester:
This operates in horizontal position. An anvil is driven by an electric motor (sideward) and it presses
the tablet at a constant load rate against a stationary anvil until the tablet breaks. The breaking force
is measured by the gauge (and this technique limits the effect of tablet weight or gravity).

FRIABILATOR
Friability test is a quality control test for tablet dosage forms which may be considered to be an official
test as given by standards which are described in some pharmacopeia such as USP. Friability may be
defined as the extent of brittleness of a tablet during/when exposed to mechanical shocks caused by
handling during manufacture, packaging and shipping. Friction and shock are the forces that most
often cause tablets to chip or break in bits. Why we test friability is because tablet hardness is not an
absolute indicator of strength since some tablets, despite been compressed into very hard tablets,
tend to chip off on attrition, losing their crown portions. Therefore, another measure of tablets
(tensile) strength is its friability. Highly friable tablets do not only lack elegance and consumer
acceptance but also, spoil the areas of manufacturing (and shipment) with dusty particles. In friability
test, the tablets are subjected to abrasion hence enabling us to check the tablet’s strength under
application of abrasive force in different manner. Friability is affected by various internal (formulation)
and external factors (instrument) e.g Punches that are in poor condition or worn out at their surface
 edges which results in “whiskering” at the tablet edge and show higher than normal friability values.
Friability of a tablet can be determined in the laboratory by using

Roche friabilator: This consist of a plastic chamber that revolves at 25 rpm, dropping the tablets
through a distance of six inches (diameter of chamber) in the friabilator. This is operate for 100
revolutions (i.e. for 4 minutes). The tablets are reweighed. Compressed tablet that lose not more than
0.5 to 1 % of the initial tablet weight are consider acceptable.

FRIABILATOR APPARATUS

• For tablet with an average weight of 0.65g or less; a sample of whole tablet correspond to 6.5g
should be taken.
• For tablet with an average weight of more than 0.65g; then take sample of 10 whole tablets.
• Result: A maximum loss of weight not greater than 0.5-1 % is acceptable
•
 DISINTEGRATION TEST APPARATUS
For a drug to be absorbed from a solid dosage form after oral administration, it must first be in
solution, and the first important step toward this condition is usually the breaking up of the solid
dosage form: tablet, capsule, etc.; a process known as disintegration. The time of disintegration is a
measure of the quality of the solid dosage form (delivery system).

If the disintegration time is too long, it may imply that the tablet is too highly compressed or the
capsule gelatine shell is not of pharmacopoeia quality. However, there could be several other reasons
that can cause this effect.

When the disintegration time is not uniform in a set of samples being analysed from the same batch,
it indicates batch inconsistency and lack of batch uniformity.

The U.S.P. device to test disintegration uses 6 glass tubes that are 3 inches long; open at the top and
10 mesh screens at the bottom end. To test for disintegration time, one tablet is placed in each tube
and the basket rack is positioned in a 1 litre beaker containing either water, simulated gastric fluid or
simulated intestinal fluid at 37 ± 2 o C such that the tablet remain 2.5 cm below the surface of the
liquid on their upward movement and not closer than 2.5 cm from the bottom of the beaker in their
downward movement. The basket containing the tablets is moved up and down through a distance of
5-6 cm (i.e 2.5 cm + 2.5 or 3.5 cm) at a frequency of 28 to 32 cycles per minute (RPM). Floating of the
tablets (especially small light weight tablets) can be prevented by placing perforated plastic discs on
each tablet. According to the official requirement of the test, the tablet must disintegrate and all
particles must pass through the 10 mesh screen in the time specified for that type of tablet. If any
residue remains, it must have a soft mass.

DISSOLUTION TEST
Dissolution is the process by which a solid solute enters a solution. Dissolution is expressed in rates
pharmaceutically as the rate of mass transfer from a drug substance (solid delivery system) into the
dissolution medium under standardized conditions of liquid/solid interface, temperature and solvent
composition. It is a dynamic property that changes with time. It happens to chemically occur by the
crystal break down into individual ions and atoms or molecules before their transport into the solvent
(medium). Dissolution is considered one of the most important official quality control tests performed
on pharmaceutical dosage forms and is now developing into a tool for predicting or anticipating the
patterns of a drug’s bioavailability. It is beginning to replace clinical studies in the determination of
bioequivalence (?). Two types of apparatus are generally used to carry out dissolution

TWELVE PLUS TWO DISSOLUTION APPARATUS

Basket Type Dissolution Apparatus:
A single tablet is placed in a small wire mesh basket attached to the bottom of the shaft connected to
a variable speed motor. The basket is immersed in a dissolution medium (as specified in monograph)
contained in a 1000 ml flask. The flask is cylindrical with a hemispherical bottom. The fluid inside the
flask is maintained at 37±0.50 C by a constant temperature bath. The motor is adjusted to turn at the
specified speed and samples of the fluid are withdrawn at intervals (starting from time zero for the
first withdrawal) to determine the amount of drug in solutions.

Paddle Type Dissolution Apparatus:

It is same as apparatus-1 except that the basket is replaced by a paddle (cone effect is common with
this technique). The dosage form is allowed to sink to the bottom of the flask before stirring. The USP
dissolution test specifies the dissolution test medium and volume, type of apparatus to be used, rpm
of the shaft and time limit of the test and assay procedure (including intervals of sample collection).
Reporting dissolution data:

The test tolerance (Q) is expressed as percentage of the labelled amount of drug dissolved in the time
limit (i.e. dissolution rate as at time limit). Decision on a dissolution test data can be carried out in
three stages if necessary.

➢ In stage 1: six tablets are tested and acceptable if all of the tablets are (equal or) greater than
the monograph tolerance limit (Q) ± 5% (i.e. 0.05).
➢ In stage 2: If the tablets fail Stage 1, an additional six tablets are tested. The tablets are
acceptable if the average of the twelve tablets (in stage 1 and 2) is greater than or equal to Q
and no unit is less than Q by 15% or more.
➢ In stage 3: If the tablets fail the test in Stage 2, an additional 12 tablets are tested. The tablets
are acceptable if the average of all the 24 tablets (in stage 1, 2 and 3) is greater or equal to Q
and not more than 2 tablet units is less than Q by 15%.

Non-Official Tests or In-House Tests of Tablet:

1. Appearance/ Description
2. Thickness and Diameter
3. Hardness
4. Organoleptic properties

Official Tests of Tablets:

1. Identification Tests
2. Friability Test
3. Disintegration Test
4. Weight Variation Test
5. Uniformity of Dosage Unit Test
 6. Dissolution Test
7. Assay Test
8. Impurities Test

Specific official Tests of Tablets

1. Microbiological Examination of Tablets
2. Acid-Neutralizing Capacity
3. Quality test of Splitting Tablets with Functional Scoring
4. Water content