QUALITY CONTROL AND QUALITY ASSURANCEOF VETERNERY DOSAGE FORMS

4-Quality control Tests For Vetenary Dosage Forms

4.1-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 hardness 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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4.2-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 hardnes

Non-Compandial tests:

1. Tablet thickness

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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.

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, …

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.

Micrometer (tablet thickness) (Tablet thickness & diameter)

Tablet packaging in blisters Tablet packaging in plastic containers

Hardness is an important criterion, since it can affect disintegration and dissolution.

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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.

"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

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:

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(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)

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 %:

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Pharmaceutical

form

Average tabletweight

(X)

Percentage

deviation

Tablets 80 mg or less 10

Tablets > 80- < 250 mg 7.5

(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

7.% 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%

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% 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 no 1 2 3 4 5 6 7 8 9

% error 0.86 12 5 5.82 1.61 0.37 0.86 1.85 5.82 1.36

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 %:

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 mgor 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)

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20

Tablet 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

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QUALITY CONTROL AND QUALITY ASSURANCEOF VETERNERY DOSAGE FORMS

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

- Friability test

- Dissolution test

- Hardness test

- Weight uniformity

- Content uniformity

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

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

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

4- During the in-process quality control testing of tablet hardness, many tablet samples were found to be very hard (10

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