Drug Dosage Forms II (PHR 312)

Lecture 6 (Continued)

Quality control (Q. C.) tests for tablets

Quality of tablets should fulfill certain specifications:
1. The tablet should include the correct dose of the drug
(Weight uniformity and content uniformity test).

2. The drug should be released from the tablet in a controlled

and reproducible way (Dissolution test).
3. The tablet should show sufficient mechanical strength to
withstand fracture and erosion during manufacturing and
handling (Hardness and friability test).
4. The appearance of the tablet should be elegant and its
weight, size and appearance should be consistent (Visual
observation, weight variation, thickness and diameter of the
tablet).

5. The tablet should be packed in a safe manner.

Quality control tests and specifications for some of these

properties are given in pharmacopoeias. The most important
for these are;
- Weight uniformity,
- Dose uniformity,
- The drug release in terms of tablet disintegration and drug
dissolution,
- Resistance of tablets to fracture in terms of friability and
harness testing, and
- The microbial quality of the product.

These factors must be controlled during production (in-process

control) and verified after production. Some test methods are
described in the pharmacopeias; others are not and thus are
referred to as "non-compendial" tests.

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A part of Good Manufacturing Practice (GMP), the production run is
monitored under control chart. At regular intervals (10-15 min.)
during the course of manufacturing, the operator must sample
specified number of tablets for testing (in-process control) e.g.
weight of tablet, tablet thickness, friability, disintegration time, …

Official Quality control tests for tablets (Compendial

tests)
British Pharmacopoeia (B.P.) & US Pharmacopoeia (USP)
1- Uniformity of content of active ingredient (Uniformity of weight
& Content uniformity)
2- Disintegration test.
3- Dissolution test.
4- Friability test.

USP mentions some Q.C. tests before the powder is compressed

e.g. powder fineness, density,…

Non-Compandial tests
There are many tests are frequently applied to tablets for which
there are non-pharmacopoeial requirements but will form a part
of manufacture's owner product specifications.
1- Tablet thickness.
2- Tablet hardness.

I- Non-Compandial tests:

1. Tablet thickness
Tablet thickness is important for tablet packaging; very thick
tablets affect packaging either in blisters or plastic containers.

The tablet thickness is determined by the diameter of the die, the

amount of fill permitted to enter the die and the force or pressure
applied during compression.
The thickness of the tablet may be measured manually or by
automatic equipment.

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Micrometer (tablet thickness) (Tablet thickness & diameter)

Tablet packaging in blisters Tablet packaging in plastic containers

2. Hardness test

In general, tablets should be sufficiently hard to resist breaking

during normal handling, packaging and shipping, and yet soft
enough to disintegrate properly after swallowing.
Hardness of the tablet is controlled by (or is affected by) the
degree of the pressure applied during the compression stage.
Hardness is an important criterion, since it can affect
disintegration and dissolution.

Special hardness testers are used for this purpose (manually or

motor driven testers).

The test measures crushing strength property defined as the

compressional force applied diametrically to a tablet which just
fracture (break) it. (The Figure below)

(N.B. In manual hardness testers, the strain rate depends on the

operator).

"Monsanto" Tablet hardness tester

A force of about 4 Kg (may be measured in Kg) is considered the

minimum requirement for a satisfactory tablet.
Certain tablets such as lozenges and buccal tablets that are
intended to dissolve slowly intentionally are made hard; others
such as immediate-release tablets are made soft.
 The Electronics Tablet Hardness, Thickness and Diameter Tester

II- Official standards (Q. C. tests) for tablets

(Compendial tests):

British Pharmacopoeia (B.P.) & US Pharmacopoeia (USP)

1- Uniformity of content of active ingredient
(Uniformity of weight & Content uniformity)
2- Disintegration test.
3- Dissolution test.
4- Friability test.
USP mentions some Q.C. tests before the powder is compressed
e.g. powder fineness, density, …

1- Uniformity of active ingredient:

(WHY?) To ensure a constant dose of drug between individual

tablets.
Traditionally, dose variation between tablets is tested in two
separate tests;
1- Weight uniformity
2- Content uniformity

If the drug forms greater part of the tablet, any variation in the
tablet weight obviously indicates a variation in the active
ingredient. (Weight uniformity test)

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If the drug is potent (USP specifies 50 mg of the active ingredient
or less), the excipients form the greater part of the tablet weight
and the correlation between the tablet weight and amount of the
active ingredient can be poor, in this case another test (Content
uniformity) must be performed.

A. Weight uniformity
B.P. design:

- Weigh 20 tablets individually (i.e. determine the weight of each

tablet alone; X1, X2, X3… X20)

- Calculate the average weight of tablets ( = Total weight of tablets )

Number of tablets

Average weight of tablets (X) = (X1+X2 +X3+…+ X20)/20

Not more than two of the individual weights (for example, X1 and
X7) deviate from the average weight (X) by more than the %
deviation shown in the table below and none deviates by more
than twice that %:

Pharmaceutical form Average tablet Percentage deviation

weight (X)
80 mg or less 10
Tablets > 80- < 250 mg 7.5
250 mg or more 5

(IMPORTANT) Example for Weight uniformity test (B.P. design):

- Weigh 20 tablets individually
(X1, X2, X3… X20)
For example;
(200, 202, 190, 205, 201, 200, 198, 190, 199, 203, 210, 220, 210, 201, 202,
199, 190, 195, 200, 200 mg)

- Calculate the average weight of tablets

X = Total weight of tablets

Number of tablets

Average weight of tablets (X) = (200+202+190+

205+201+200+198+190+199+ 203+210+220+210+ 201+202+ 199+
190+195+200+200)/20 = 201.75 mg

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 % Error for a tablet=
Difference between Actual tablet weight & Average tablet weight x 100
Average tablet weight

% error for tablet 1= 201.75 - 200/201.75 x 100= 0.86%

% error for tablet 2= 202 - 201.75/201.75 x 100= 0.12%
% error for tablet 3= 201.75 - 190/201.75 x 100= 5.82%
% error for tablet 4= 205 - 201.75/201.75 x 100= 1.61%
% error for tablet 5= ……………
Calculate % error for each tablet

Tablet
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
no
%
0.86 0.12 5.82 1.61 0.37 0.86 1.85 5.82 1.36 0.6 4.08 9.04 4.08 0.37 0.12 1.36 5.82 3.34 0.86 0.86
error

Pharmacopoeial requirement:
Not more than two of the individual tablet weights deviate from
the average weight (X) by more than 7.5% according to the
following table and none deviate by double this %:

Pharmaceutical form Average tablet Percentage deviation

weight (X)
80 mg or less 10
Tablets > 80- < 250 mg 7.5
250 mg or more 5

Test result: Only one tablet (tablet number 12) deviated >7.5%,
and this deviation (%error 9.04 %) is less than 15 %, i.e. tablets
passed this test successfully

B. Content uniformity
USP defines content uniformity test for tablets containing 50 mg
or less of drug substance in case of uncoated tablets and for
all sugar coated tablets regardless to the drug content.

USP design:
Ten tablets are individually assayed for their content (according
to the method described in the individual monograph)
The requirements for content uniformity are met if the amount of
the active ingredient in each tablet lies within the range of 85-
115 % of the label claim.

(If one or more tablet does not meet these criteria, additional tests as
prescribed in the USP are required)

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If content uniformity test is required, the weight uniformity test is not
required

I- Match:
- Friability test

1- USP quality control test performed for tablets containing - Dissolution test
20mg drug to ensure that each include the correct dose

2- Quality control test performed for tablets to ensure that - Hardness test
each shows sufficient mechanical strength

3- Quality control test performed for tablets to ensure that - Weight uniformity
the drug is released in a controlled and reproducible way

- Content uniformity

II- Put Write or Wrong:

1- Tablet thickness and hardness test are non-compendial quality control tests

2- Tablet thickness is important for tablet packaging

3- Hardness does not affect disintegration or dissolution of the tablet

4- If content uniformity test is required, the weight uniformity test is not required

5- 1 Kg is a suitable hardness value for a satisfactory buccal tablet

6- Disintegration test is a Pharmacopoeial Requirement for chewable tablets

7- Content uniformity test is essential for all sugar coated tablets regardless to
their drug content

8- In weight uniformity test, tablets are individually assayed for their content

III- What is the only suitable Quality Control Test for

Dexamethasone tablet (0.5 mg/Tab), to ensure a constant dose of
drug between individual tablets
IV- During the in-process quality control testing of tablet
hardness, many tablet samples were found to be very hard (10 Kg)

What are the possible reasons?

What are your suggestions?
What are the expected problems with these hard tablets?

Remember
No Quizzes will be held next week during lab sessions (16, 18/11/2009)

Next Quiz (in lab 23, 25/11/2009)

Tablet coating and Quality control tests for tablets

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